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Kong L, Sun J, Abedi-Firouzjah R. Emerging treatment strategies in dry eye disease: Potential of blood-derived approaches and natural plant-based products. Exp Eye Res 2025; 251:110217. [PMID: 39709048 DOI: 10.1016/j.exer.2024.110217] [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: 07/29/2024] [Revised: 12/10/2024] [Accepted: 12/17/2024] [Indexed: 12/23/2024]
Abstract
Dry eye disease (DED) is a common ocular condition characterized by chronic inflammation and tear film disruption. It affects millions of people worldwide, causing significant eye discomfort and vision disturbances. Despite its prevalence, DED remains a complex condition that is not yet fully understood. It can arise from various ocular pathologies, including endocrinological disorders such as diabetes and Graves' orbitopathy. Natural products, including plant- and blood-based therapies, have shown promise in alleviating DED symptoms and may represent effective therapeutic approaches. In this study, we review recent research on natural product treatments for DED, focusing on blood-derived therapies (e.g., autologous serum, albumin serum, and allogeneic serum) and plant-based compounds such as omega-3 fatty acids (O3FA), omega-6 fatty acids (O6FA), antioxidants, polyphenols, and flavonoids. Additionally, we examine the efficacy, mechanisms of action, and delivery systems of these treatments, highlighting the potential of blood-derived therapies, polyphenols, and flavonoids to improve or treat DED through multiple mechanisms. However, the use of these natural products as instilled drugs is limited by challenges such as solubility, stability, and biological barriers. Finally, we discuss drug delivery systems and structural modifications designed to enhance the therapeutic effects of these treatments, emphasizing their potential in managing DED.
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Affiliation(s)
- Lingli Kong
- Department of Otorhinology, Gongshu District Daguan Shangtang Street Community Health Service Center, Hangzhou, 310000, China
| | - Jiali Sun
- Department of Ophthalmology, Hangzhou Huaxia Eye Hospital, Hangzhou, 310000, China.
| | - Razzagh Abedi-Firouzjah
- Department of Medical Physics, Radiobiology and Radiation Protection, School of Medicine, Babol University of Medical Sciences, Babol, Iran
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Sharma R, Sharma A, Kakkar V, Saini K, Balakrishna JP, Nirankari VS. Autologous Serum Eye Drops Diluted with Cyclosporine A 0.05% and Sodium Hyaluronate 0.1%: An Experimental Comparative Study. Curr Eye Res 2025; 50:23-31. [PMID: 39099132 DOI: 10.1080/02713683.2024.2385442] [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: 09/21/2023] [Revised: 06/08/2024] [Accepted: 07/18/2024] [Indexed: 08/06/2024]
Abstract
PURPOSE The purpose of this study was to assess in-vitro efficacy of a suffusion of autologous serum withcyclosporine 0.05% (CsA) and sodium hyaluronate 0.1% (SH). METHODS The expression of proinflammatory markers interleukin 6 (IL-6) and TNF-Alpha (TNF-α) in limbal epithelial cells was evaluated. Also, assessment of the stability of epithelial growth factor and transforming growth factor-beta (EGF, TGF-β) in the 50% combinations with autologous serum (AS) was done. The characteristics (pH, density, osmolality) of the two combinations were also evaluated. Additionally, cytotoxicity effect of given test compounds was evaluated on human limbal epithelial cells (LEpiC). RESULTS The percentage of cells expressing IL-6 subjected to AS + SH and AS + CsA were 6.23% and 5.69% respectively. There was no significant difference in percentage of cells expressing TNF-α between the formulations (5.87%, 5.83% respectively). The growth factors; EGF and TGF-β remained stable forone month duration (on 2 and 4 weeks) at 4 °C without significant difference between the time intervals tested. The results of MTT assay suggested that limbal epithelial cells treated with AS + CsA and AS + SH combinations showed minimal toxicity however it was not significant statistically (p ≤ 0.05). CONCLUSION Two test combinations (AS + CsA, AS + SH) showed stable growth factors (EGF, TGF-β) and good anti-inflammatory property against pro-inflammatory markers. Also, the 2 combinations were found safe on cultured limbal epithelial cells. The novel combination of autologous serum in CsA may provide added benefit in dry eye disease (DED) through their combined anti-inflammatory and epitheliotropic effects.
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Affiliation(s)
- Rajan Sharma
- Dr. Ashok Sharma's Cornea Centre, Chandigarh (U.T.), India
| | - Ashok Sharma
- Dr. Ashok Sharma's Cornea Centre, Chandigarh (U.T.), India
| | - Vandita Kakkar
- University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh (U.T.), India
| | - Komal Saini
- University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh (U.T.), India
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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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4
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He CZ, Zeng ZJ, Liu JQ, Qiu Q, He Y. Autologous serum eye drops for patients with dry eye disease: a systematic review and meta-analysis of randomized controlled trials. Front Med (Lausanne) 2024; 11:1430785. [PMID: 39346942 PMCID: PMC11427303 DOI: 10.3389/fmed.2024.1430785] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Accepted: 09/03/2024] [Indexed: 10/01/2024] Open
Abstract
Background Dry eye disease (DED) is highly prevalent worldwide, leading to increased medical costs, economic burdens on families and society, and a diminished quality of life for patients. The utilization of autologous serum eye drops (ASEDs) for the treatment of DED is progressively rising. Objective To further evaluate the efficacy and safety of ASEDs in the treatment of DED. Methods A thorough search for randomized controlled trials (RCTs) was conducted across eight databases, including PubMed, EMBASE, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang, SinoMed, and VIP. This search encompassed the inception of each database up to April 1, 2024, with a specific focus on identifying RCTs evaluating the efficacy and safety of ASEDs for the treatment of DED. Data analysis was conducted utilizing Stata 15.0 software and the Cochrane Risk of Bias Assessment Tool was utilized to appraise the literature's quality. Results The study encompassed 12 RCTs. In comparison to the use of artificial tears (AT), patients diagnosed with DED who utilized ASEDs displayed elevated the Schirmer test (ST) scores [WMD = 2.35, 95% CI (1.45, 3.24), p < 0.001] and tear-film breakup time (TBUT) scores [WMD = 2.83, 95% CI (2.27, 3.39), p < 0.001], decreased Corneal fluorescence staining (CFS) scores [SMD = -2.11, 95% CI (-3.07, -1.15), p < 0.001] and the Ocular Surface Disease Index (OSDI) scores [WMD = -10.54, 95% CI (-13.31, -7.77), p < 0.001], and experienced a reduced frequency of adverse events [RR = 0.36, 95% CI (0.13, 0.99), p = 0.048]. Conclusion In this study, ASEDs had been shown to enhance tear secretion, extend tear film break-up time, mitigate corneal epithelial damage, ameliorate OSDI scores, and exhibit greater safety compared to AT.
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Affiliation(s)
- Chang-Zhu He
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Zhao-Jun Zeng
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jun Qiao Liu
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Qin Qiu
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yu He
- Department of Ophthalmology, Chengdu First People's Hospital/Chengdu Integrated TCM and Western Medicine Hospital, Chengdu, China
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Ghenciu LA, Hațegan OA, Bolintineanu SL, Dănilă AI, Faur AC, Prodan-Bărbulescu C, Stoicescu ER, Iacob R, Șișu AM. Immune-Mediated Ocular Surface Disease in Diabetes Mellitus-Clinical Perspectives and Treatment: A Narrative Review. Biomedicines 2024; 12:1303. [PMID: 38927510 PMCID: PMC11201425 DOI: 10.3390/biomedicines12061303] [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: 05/22/2024] [Revised: 06/06/2024] [Accepted: 06/10/2024] [Indexed: 06/28/2024] Open
Abstract
Diabetes mellitus (DM) is a chronic metabolic disorder marked by hyperglycemia due to defects in insulin secretion, action, or both, with a global prevalence that has tripled in recent decades. This condition poses significant public health challenges, affecting individuals, healthcare systems, and economies worldwide. Among its numerous complications, ocular surface disease (OSD) is a significant concern, yet understanding its pathophysiology, diagnosis, and management remains challenging. This review aims to explore the epidemiology, pathophysiology, clinical manifestations, diagnostic approaches, and management strategies of diabetes-related OSD. The ocular surface, including the cornea, conjunctiva, and associated structures, is vital for maintaining eye health, with the lacrimal functional unit (LFU) playing a crucial role in tear film regulation. In DM, changes in glycosaminoglycan metabolism, collagen synthesis, oxygen consumption, and LFU dysfunction contribute to ocular complications. Persistent hyperglycemia leads to the expression of cytokines, chemokines, and cell adhesion molecules, resulting in neuropathy, tear film abnormalities, and epithelial lesions. Recent advances in molecular research and therapeutic modalities, such as gene and stem cell therapies, show promise for managing diabetic ocular complications. Future research should focus on pathogenetically oriented therapies for diabetic neuropathy and keratopathy, transitioning from animal models to clinical trials to improve patient outcomes.
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Affiliation(s)
- Laura Andreea Ghenciu
- Department of Functional Sciences, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania;
| | - Ovidiu Alin Hațegan
- Discipline of Anatomy and Embriology, Medicine Faculty, ‘Vasile Goldis’ Western University of Arad, Revolution Boulevard 94, 310025 Arad, Romania
| | - Sorin Lucian Bolintineanu
- Department of Anatomy and Embriology, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania; (S.L.B.); (A.-I.D.); (A.C.F.); (C.P.-B.); (R.I.); (A.M.Ș.)
| | - Alexandra-Ioana Dănilă
- Department of Anatomy and Embriology, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania; (S.L.B.); (A.-I.D.); (A.C.F.); (C.P.-B.); (R.I.); (A.M.Ș.)
| | - Alexandra Corina Faur
- Department of Anatomy and Embriology, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania; (S.L.B.); (A.-I.D.); (A.C.F.); (C.P.-B.); (R.I.); (A.M.Ș.)
| | - Cătălin Prodan-Bărbulescu
- Department of Anatomy and Embriology, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania; (S.L.B.); (A.-I.D.); (A.C.F.); (C.P.-B.); (R.I.); (A.M.Ș.)
- Doctoral School, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
- IInd Surgery Clinic, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
| | - Emil Robert Stoicescu
- Field of Applied Engineering Sciences, Specialization Statistical Methods and Techniques in Health and Clinical Research, Faculty of Mechanics, ‘Politehnica’ University Timisoara, Mihai Viteazul Boulevard No. 1, 300222 Timisoara, Romania;
- Department of Radiology and Medical Imaging, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
- Research Center for Pharmaco-Toxicological Evaluations, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
| | - Roxana Iacob
- Department of Anatomy and Embriology, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania; (S.L.B.); (A.-I.D.); (A.C.F.); (C.P.-B.); (R.I.); (A.M.Ș.)
- Doctoral School, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
- Field of Applied Engineering Sciences, Specialization Statistical Methods and Techniques in Health and Clinical Research, Faculty of Mechanics, ‘Politehnica’ University Timisoara, Mihai Viteazul Boulevard No. 1, 300222 Timisoara, Romania;
| | - Alina Maria Șișu
- Department of Anatomy and Embriology, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania; (S.L.B.); (A.-I.D.); (A.C.F.); (C.P.-B.); (R.I.); (A.M.Ș.)
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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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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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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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9
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Badami KG, McKellar M. Reactions to serum eye drops-New Zealand experience and review of the literature. Transfus Med 2024; 34:61-65. [PMID: 37947132 DOI: 10.1111/tme.13017] [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: 07/18/2023] [Revised: 10/09/2023] [Accepted: 10/30/2023] [Indexed: 11/12/2023]
Abstract
BACKGROUND Serum eye drops (SED) are used to treat ocular surface disease. Reactions to SED are poorly documented. METHODS We present our experience of self-reported reactions in New Zealand to SED (25%; autologous, allogeneic, or both) between 2003 and 2023, and a focused review of the literature. RESULTS In total, 1067 patients received SED treatment (562 autologous, 318 allogeneic, and 187 both). Three (0.5% of those treated with allogeneic SED) reported reactions. All appeared to be allergic. All were associated with allogeneic SED. We have information on two patients: one had an eye reaction; in the other, the gastrointestinal tract was involved. The literature contains few reports of reactions to SED. They have involved both autologous and allogeneic SED, and various SED concentrations. None appears to have been severe. Notably, no eye or systemic infections have been reported. CONCLUSIONS Information on the types and frequencies of reactions to SED is poor. This may be due to: serum being less likely to cause reactions; eyes being resistant to reactions; reactions being rare, and insufficient use of SED having occurred; under-reporting related to SED use at home and reactions being mild. More robust monitoring for reactions to SED is needed.
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10
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Leonhard M, Turner C, Langenbucher A, Flockerzi E, Seitz B. [Comparison of the Effect of Autologous Serum on Therapy Resistant Corneal Erosions and Ulcers on the Corneal Graft vs. the Patient's Own Cornea]. Klin Monbl Augenheilkd 2024; 241:102-109. [PMID: 37164338 DOI: 10.1055/a-2091-0111] [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: 05/12/2023]
Abstract
PURPOSE The aim of this study is to compare the healing of corneal epithelial defects or ulcers on the corneal graft in comparison with the patient's own cornea after treatment with 100%, undiluted autologous serum eye drops. METHODS In a retrospective study over 7 years, we analysed 263 treatments with autologous serum eye drops of persistent corneal epithelial defects (erosions [88%] vs. ulcers [12%]). We compared the epithelial healing tendency of patients with defects on their own cornea (51.9%) vs. patients who had previously undergone penetrating keratoplasty (48.1%). Complete epithelial healing during the 28 days of treatment was considered as therapeutic success. In addition, the recurrence rate of the epithelial defects after finishing the therapy was analysed. RESULTS 88.2% of the epithelial defects healed during 28 days of therapy. The recurrence rate during follow-up was 5.1%. There was no significant difference with respect to success rate between corneal defects on the patient's own cornea (87.8%) and on the graft (88.6%; p = 0.137). There was a significantly lower success rate for corneal ulcers (74.2%) than for erosions (90.3%; p < 0.001). The recurrence rate of erosions was 4.4%, vs. 4.3% in ulcers during follow-up. CONCLUSION The results of our study suggest that autologous serum eye drops are a non-invasive and safe alternative treatment for persistent corneal epithelial defects - with no significant difference in patients with a defect on their own cornea vs. defects on the corneal graft. The success rate, but not the recurrence rate, is significantly worse in ulcers than in erosions.
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Affiliation(s)
- Marie Leonhard
- Klinik für Augenheilkunde, Universitätsklinikum des Saarlandes (UKS), Homburg/Saar, Deutschland
| | - Christina Turner
- Klinik für Augenheilkunde, Universitätsklinikum des Saarlandes (UKS), Homburg/Saar, Deutschland
| | - Achim Langenbucher
- Institut für Experimentelle Ophthalmologie, Universitätsklinikum des Saarlandes, Homburg/Saar, Deutschland
| | - Elias Flockerzi
- Klinik für Augenheilkunde, Universitätsklinikum des Saarlandes (UKS), Homburg/Saar, Deutschland
| | - Berthold Seitz
- Klinik für Augenheilkunde, Universitätsklinikum des Saarlandes (UKS), Homburg/Saar, Deutschland
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11
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Posarelli M, Romano D, Tucci D, Giannaccare G, Scorcia V, Taloni A, Pagano L, Borgia A. Ocular-Surface Regeneration Therapies for Eye Disorders: The State of the Art. BIOTECH 2023; 12:48. [PMID: 37366796 DOI: 10.3390/biotech12020048] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Revised: 06/10/2023] [Accepted: 06/13/2023] [Indexed: 06/28/2023] Open
Abstract
The ocular surface is a complex structure that includes cornea, conjunctiva, limbus, and tear film, and is critical for maintaining visual function. When the ocular-surface integrity is altered by a disease, conventional therapies usually rely on topical drops or tissue replacement with more invasive procedures, such as corneal transplants. However, in the last years, regeneration therapies have emerged as a promising approach to repair the damaged ocular surface by stimulating cell proliferation and restoring the eye homeostasis and function. This article reviews the different strategies employed in ocular-surface regeneration, including cell-based therapies, growth-factor-based therapies, and tissue-engineering approaches. Dry eye and neurotrophic keratopathy diseases can be treated with nerve-growth factors to stimulate the limbal stem-cell proliferation and the corneal nerve regeneration, whereas conjunctival autograft or amniotic membrane are used in subjects with corneal limbus dysfunction, such as limbal stem-cell deficiency or pterygium. Further, new therapies are available for patients with corneal endothelium diseases to promote the expansion and migration of cells without the need of corneal keratoplasty. Finally, gene therapy is a promising new frontier of regeneration medicine that can modify the gene expression and, potentially, restore the corneal transparency by reducing fibrosis and neovascularization, as well as by stimulating stem-cell proliferation and tissue regeneration.
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Affiliation(s)
- Matteo Posarelli
- St. Paul's Eye Unit, Department of Corneal Diseases, Royal Liverpool University Hospital, Liverpool L7 8YE, UK
- Ophthalmology Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, Italy
| | - Davide Romano
- Eye Clinic, Department of Neurological and Vision Sciences, University of Brescia, 25123 Brescia, Italy
- Eye Unit, University Hospitals of Leicester, NHS Trust, Leicester LE1 5WW, UK
| | - Davide Tucci
- Department of Biomedical and Surgical Sciences, Section of Ophthalmology, S. Maria Della Misericordia Hospital, University of Perugia, 06123 Perugia, Italy
| | - Giuseppe Giannaccare
- Department of Ophthalmology, University Magna Græcia of Catanzaro, 88100 Catanzaro, Italy
| | - Vincenzo Scorcia
- Department of Ophthalmology, University Magna Græcia of Catanzaro, 88100 Catanzaro, Italy
| | - Andrea Taloni
- Department of Ophthalmology, University Magna Græcia of Catanzaro, 88100 Catanzaro, Italy
| | - Luca Pagano
- St. Paul's Eye Unit, Department of Corneal Diseases, Royal Liverpool University Hospital, Liverpool L7 8YE, UK
| | - Alfredo Borgia
- St. Paul's Eye Unit, Department of Corneal Diseases, Royal Liverpool University Hospital, Liverpool L7 8YE, UK
- Eye Unit, Humanitas-Gradenigo Hospital, 10153 Turin, Italy
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Nadelmann JB, Bunya VY, Ying GS, Hua P, Massaro-Giordano M. Effect of Autologous Platelet-Rich Plasma Drops in the Treatment of Ocular Surface Disease. Clin Ophthalmol 2022; 16:4207-4213. [PMID: 36544899 PMCID: PMC9762402 DOI: 10.2147/opth.s391536] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Accepted: 11/23/2022] [Indexed: 12/15/2022] Open
Abstract
Purpose Platelet rich plasma (PRP) is an autologous preparation that concentrates platelets in a small volume of plasma. The purpose of this study was to determine if PRP eye drops improved the symptoms and signs of ocular surface disease. Patients and Methods A retrospective case series was conducted of patients who were prescribed PRP eye drops. Subjects were excluded if they did not have follow-up, underwent intraocular surgery prior to follow-up, received nerve growth factor treatments, or did not have a baseline examination with photography. Symptoms were assessed using the Ocular Surface Disease Index (OSDI). Patients also underwent a slit lamp exam, ocular surface staining with fluorescein and lissamine green, and Schirmer testing. Results The charts of 47 patients treated with PRP drops for ocular surface disease were reviewed. Sixty-four eyes of 32 patients were included in the study who had photographs of lissamine green staining taken at baseline and at follow-up. Thirteen patients (28%) had ocular graft-versus-host disease, 16 patients (34%) had Sjögren's syndrome, and 4 patients (8.5%) had rheumatoid arthritis. There was a statistically significant decrease in OSDI score from baseline to follow-up (39.5 vs 30.8 points, p = 0.02). Among the 64 eyes included, 9 (14%) had an improvement in conjunctival lissamine green staining, while 6 (9%) had an increase in staining at follow-up. Among the 20 eyes with Schirmer testing, there was a borderline significant increase in score from baseline to follow-up (5.9 vs 9.7, p = 0.06). Among the 44 eyes that had corneal fluorescein staining (CFS) reported, 8 (18.2%) had decreased staining and 2 (4.5%) had increased staining at follow-up. Conclusion Treatment with PRP drops was associated with a significant improvement in symptoms in patients with ocular surface disease. Future larger prospective studies are needed to further evaluate the efficacy of PRP drops for treating ocular surface disease.
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Affiliation(s)
- Jennifer B Nadelmann
- Department of Ophthalmology, Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Department of Ophthalmology, Weill Cornell Medicine, New York, NY, USA
| | - Vatinee Y Bunya
- Department of Ophthalmology, Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Gui-Shuang Ying
- Center for Preventive Ophthalmology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USA
| | - Peiying Hua
- Center for Preventive Ophthalmology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USA
| | - Mina Massaro-Giordano
- Department of Ophthalmology, Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
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Sugar A, Hussain M, Chamberlain W, Dana R, Kelly DP, Ta C, Irvine J, Daluvoy M, Perez V, Olson J, Jhanji V, Walts TA, Stulting RD, Waller EK, Jagirdar N. A Randomized Trial of Topical Fibrinogen-Depleted Human Platelet Lysate Treatment of Dry Eye Secondary to Chronic Graft-versus-Host Disease. OPHTHALMOLOGY SCIENCE 2022; 2:100176. [PMID: 36245754 PMCID: PMC9562362 DOI: 10.1016/j.xops.2022.100176] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Revised: 05/25/2022] [Accepted: 05/26/2022] [Indexed: 11/29/2022]
Abstract
Purpose The purpose of the study was to evaluate, as a pilot trial, safety and tolerability of CAM-101 10% and 30% topical ophthalmic fibrinogen-depleted human platelet lysate (FD hPL) solution in patients with dry eye disease (DED) secondary to graft-versus-host disease (GvHD) after 6 weeks of treatment. Design A phase I/II, pilot, prospective, multicenter, randomized, double-masked clinical trial. Participants Patients with DED secondary to GvHD. Methods Sixty-four adult patients were stratified by "symptom severity" (Ocular Surface Disease Index [OSDI], ocular discomfort Visual Analog Scale (VAS), ocular symptom frequency, and use of artificial tears) and then randomized 1:1:1 to CAM-101 (FD hPL) at 10% or 30% concentration or an electrolyte (Plasma-Lyte A) vehicle control, 1 drop in both eyes, 4 times daily, for 42 days. After 42 days, control patients were offered 42 days of open-label treatment with 30% FD hPL. Main Outcome Measures Primary outcome safety measures were ocular and systemic adverse events and the number of patients in each group with clinically significant change from normal to abnormal in any ocular findings. Secondary outcomes were changes from baseline to day 42 in ocular discomfort, OSDI, fluorescein corneal staining, and lissamine green conjunctival staining relative to the vehicle control. The ocular symptom frequency was assessed on a 100-point VAS. Results FD hPL 10% and 30% were safe and well tolerated. Relative to the vehicle control, significant decreases from baseline to day 42 were seen in the FD hPL 30% group with regard to ocular discomfort (mean decrease = -18.04; P = 0.018), frequency of burning/stinging (-20.23; P = 0.022), eye discomfort (-32.97; P < 0.001), eye dryness (-21.61; P = 0.020), pain (-15.12; P = 0.044), photophobia (-24.33; P = 0.0125), and grittiness (-20.08; P = 0.0185). Decreases were also seen for itching and foreign body sensation, though not statistically significant. Improvements were seen in tear breakup time (mean increase = 1.30 seconds; P = 0.082) and the investigator's global evaluation 4-point scale (mean decrease = -0.86; P = 0.026). Corneal fluorescein staining was not improved. The OSDI had a mean decrease of -8.88 compared to the vehicle, although not statistically significant. Conclusions Fibrinogen-depleted human platelet lysate appears to be well tolerated, with no significant toxicity at concentrations of 10% and 30%. These initial data suggest some efficacy, especially for subjective outcome measures relative to baseline assessments and treatment with the vehicle, but larger studies are needed to confirm these effects.
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Key Words
- AE, adverse event
- ASTs, autologous serum tears
- CI, confidence interval
- DED, dry eye disease
- Dry eye disease
- FD hPL, fibrinogen-depleted human platelet lysate
- Graft versus host disease
- GvHD, graft-versus-host disease
- HSCT, hematopoietic stem cell transplant
- Human platelet
- OSDI, ocular surface disease index
- Ocular surface
- PRP, platelet-rich plasma
- SAE, severe adverse event
- Serum tears
- VAS, Visual Analog Scale
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Affiliation(s)
- Alan Sugar
- WK Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan
| | - Munira Hussain
- WK Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan
| | - Winston Chamberlain
- Casey Eye Institute, and Department of Ophthalmology, Oregon Health and Science University, Portland, Oregon
| | - Reza Dana
- Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
| | | | - Christopher Ta
- Department of Ophthalmology, School of Medicine, Stanford University, Stanford, California
| | - John Irvine
- Doheny Eye Center, UCLA, Los Angeles, California
| | | | - Victor Perez
- Duke University Eye Center, Durham, North Carolina
| | - Joshua Olson
- Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota
| | - Vishal Jhanji
- UPMC Eye Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | | | - Robert Doyle Stulting
- Cambium Medical Technologies LLC, Atlanta, Georgia
- Woolfson Eye Institute, Atlanta, Georgia
| | - Edmund K. Waller
- Cambium Medical Technologies LLC, Atlanta, Georgia
- Winship Cancer Institute of Emory University, Atlanta, Georgia
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Mohammed MA, Allam IY, Shaheen MS, Lazreg S, Doheim MF. Lacrimal gland injection of platelet rich plasma for treatment of severe dry eye: a comparative clinical study. BMC Ophthalmol 2022; 22:343. [PMID: 35964112 PMCID: PMC9375917 DOI: 10.1186/s12886-022-02554-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Accepted: 07/27/2022] [Indexed: 11/24/2022] Open
Abstract
Background We aimed to assess the efficacy of the injections of platelet rich plasma (PRP) for the treatment of severe dry eye disease (DED). Results In this retrospecitve interventional clinincal study, we included 28 eyes of 14 patients with severe DED who were diagnosed with Sjogren syndrome. Each patient received unilateral lacrimal gland injection of PRP at days 0, 30, 60 and 90 days while the other eye served as control group who received preservative free eye drops. We objectively assessed parameters at baseline, 1 month, 2 months and 3 months including ocular surface analyzer (OSA) namely; noninvasive tear breakup times (NIBUT), tear meniscus height (TMH), lipid layer thickness (LLT) in addition to the Schirmer test I, corneal fluorescein staining (CFS) and meiboscore. The mean age was 43.4 ± .7.85 years. Comparing different parameters, baseline data showed non-significant difference between injected eye group and control group. After 1 and 3 months of follow up, there were significant differences between both groups regarding NITBUT, TMH, LLT, CFS and Schirmer test, with p < 0.001 in favor of PRP group. Conclusion Injection of PRP in lacrimal gland is simple, safe, and effective technique in treatment of severe dry eye; proved by improvement of tear film parameters through subjective and objective assessment. Further studies are needed to standardize the technique and to confirm these results.
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Affiliation(s)
- Mai A Mohammed
- Ophthalmology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
| | - Ibrahim Y Allam
- Ophthalmology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | | | - Sihem Lazreg
- Cabinet Ophtalmologie, Alger Centre, Algiers, Algeria
| | - Mohamed Fahmy Doheim
- Ophthalmology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
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15
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Rawat P, Agrawal R, Bhaisare V, Walia S, Kori N, Gupta R. Autologous platelet-rich plasma eye drop versus artificial tear eye drop for symptomatic dry eye disease: A prospective comparative interventional study. Indian J Ophthalmol 2022; 70:1549-1553. [PMID: 35502024 PMCID: PMC9333043 DOI: 10.4103/ijo.ijo_2595_21] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Revised: 11/02/2021] [Accepted: 01/24/2022] [Indexed: 11/24/2022] Open
Abstract
Purpose To evaluate and compare the efficacy of autologous platelet-rich plasma (aPRP) eye drop and artificial tear (AT) eye drop in moderate to severe symptomatic dry eye disease (DED). Methods This prospective interventional study included 121 eyes of 61 patients of moderate to severe DED. Patients were divided into aPRP (31 patients) and AT (30 patients) group. Ocular Surface Disease Index (OSDI) score, tear film breakup time (TBUT) (s), corneal fluorescein staining (CFS) score, and Schirmer test score (mm) of both the groups were evaluated and compared pre-treatment and post-treatment at the end of 3 months. Results The mean age of the aPRP group and AT group was 52.8 ± 12.8 years and 55.5 ± 13.4 years, respectively. At the end of 3 months, OSDI score reduced more in the aPRP group as compared to AT group, and the mean difference (-22.7) was statistically significant (P < 0.001). There was no significant difference in post-treatment Schirmer test score between the two groups (P = 0.44). Post-treatment improvement in TBUT and CFS score in the aPRP group was significantly higher in the aPRP group as compared to that in the AT group (P < 0.05). Bruising at the site of blood withdrawal was noted in two patients in the aPRP group. Conclusion aPRP is safe and more effective than AT in treating patients with moderate to severe symptomatic DED.
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Affiliation(s)
- Preeti Rawat
- Department of Ophthalmology, Mahatma Gandhi Memorial Medical College, M. Y. Hospital, Indore, Madhya Pradesh, India
| | - Ritika Agrawal
- Department of Ophthalmology, Mahatma Gandhi Memorial Medical College, M. Y. Hospital, Indore, Madhya Pradesh, India
| | - Vijay Bhaisare
- Department of Ophthalmology, Mahatma Gandhi Memorial Medical College, M. Y. Hospital, Indore, Madhya Pradesh, India
| | - Shweta Walia
- Department of Ophthalmology, Mahatma Gandhi Memorial Medical College, M. Y. Hospital, Indore, Madhya Pradesh, India
| | - Neetu Kori
- Department of Ophthalmology, Mahatma Gandhi Memorial Medical College, M. Y. Hospital, Indore, Madhya Pradesh, India
| | - Rishi Gupta
- Department of Ophthalmology, Mahatma Gandhi Memorial Medical College, M. Y. Hospital, Indore, Madhya Pradesh, India
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Abstract
PURPOSE To describe the efficacy of autologous serum (AS) eye drops to reverse severe contact lens (CL)-induced limbal stem cell (LSC) deficiency (LSCD). METHODS This is a prospective, uncontrolled, interventional case series that enrolled 20 eyes of 14 consecutive patients diagnosed with severe CL-induced LSCD at presentation, based on clinical examination, at a tertiary referral center for the period December 2016 to December 2018. All eyes underwent AS treatment for at least 2 weeks with a follow-up for at least 2 months. Demographic data and treatment outcomes were collected and analyzed. RESULTS The mean patient age at presentation was 30.5 years (range, 19-49 years). The mean duration of soft contact lens wear was 15.6 years (SD, 7.58 years; range, 5-31 years). All study eyes had pain and blurred vision at presentation. All eyes had recurrent or persistent corneal epithelial defect, stromal scarring and opacity, and superficial vascularization and peripheral pannus at presentation. Aggressive treatment with AS succeeded in all eyes. Signs and symptoms of LSCD stabilized in all eyes within 2 weeks and resolved in 6 eyes (30.0%) in 2 weeks, 9 eyes (45.0%) in 4 weeks, and 5 eyes (25.0%) in 8 weeks. The mean follow-up time was 9.45 ± 1.79 weeks (range, 8-24 weeks). CONCLUSIONS Early identification and aggressive treatment of the ocular surface disease with AS can medically reverse severe CL-induced LSCD and prevent the need for surgical intervention.
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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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18
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Fini ME, Jeong S, Wilson MR. Therapeutic Potential of the Molecular Chaperone and Matrix Metalloproteinase Inhibitor Clusterin for Dry Eye. Int J Mol Sci 2020; 22:E116. [PMID: 33374364 PMCID: PMC7794831 DOI: 10.3390/ijms22010116] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 12/19/2020] [Accepted: 12/21/2020] [Indexed: 12/29/2022] Open
Abstract
Evidence is presented herein supporting the potential of the natural homeostatic glycoprotein CLU (clusterin) as a novel therapeutic for the treatment of dry eye. This idea began with the demonstration that matrix metalloproteinase MMP9 is required for damage to the ocular surface in mouse dry eye. Damage was characterized by degradation of OCLN (occludin), a known substrate of MMP9 and a key component of the paracellular barrier. Following up on this finding, a yeast two-hybrid screen was conducted using MMP9 as the bait to identify other proteins involved. CLU emerged as a strong interacting protein that inhibits the enzymatic activity of MMP9. Previously characterized as a molecular chaperone, CLU is expressed prominently by epithelia at fluid-tissue interfaces and secreted into bodily fluids, where it protects cells and tissues against damaging stress. It was demonstrated that CLU also protects the ocular surface in mouse dry eye when applied topically to replace the natural protein depleted from the dysfunctional tears. CLU is similarly depleted from tears in human dry eye. The most novel and interesting finding was that CLU binds selectively to the damaged ocular surface. In this position, CLU protects against epithelial cell death and barrier proteolysis, and dampens the autoimmune response, while the apical epithelial cell layer is renewed. When present at high enough concentration, CLU also blocks staining by vital dyes used clinically to diagnose dry eye. None of the current therapeutics have this combination of properties to "protect, seal, and heal". Future work will be directed towards human clinical trials to investigate the therapeutic promise of CLU.
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Affiliation(s)
- M. Elizabeth Fini
- New England Eye Center, Tufts Medical Center and Department of Ophthalmology, Tufts University School of Medicine, Program in Pharmacology & Drug Development, Graduate School of Biomedical Sciences Tufts University, Boston, MA 02111, USA
| | - Shinwu Jeong
- Department of Ophthalmology, USC Roski Eye Institute, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA 90089, USA;
| | - Mark R. Wilson
- The Illawarra Health and Medical Research Institute, Molecular Horizons and the School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, NSW 2522, Australia;
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20
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Yang Y, Zhu X, Yang J, Shi A, Jiang M, Peng Y, Li M, Wang Y, Yuan H. An Environmental Control Experiment for Contamination of the Production and Storage of 20% Autologous Serum Eye Drops. Curr Eye Res 2020; 45:1364-1368. [PMID: 32150475 DOI: 10.1080/02713683.2020.1741008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
Purpose: To investigate the sterility of autologous serum eye drops used for ocular surface diseases. Methods: A total of 100 patients were enrolled. The serum was prepared as follows: 20% serum (20% S), 20% serum with dexamethasone (0.02 mg/ml) (20% S + Dex), and 20% serum with levofloxacin (0.1 mg/ml) (20% S + Lev). Serum samples were collected for normal microbial cultivation at 1, 3, 5, 7, 10, 14, 21, and 28 days. The last samples were also assessed on the 28th day by airtight microbial cultivation. Results: A total of 2400 samples were cultured, and the bacterial contamination rates of 20% S, 20% S+ Dex, and 20% S + Lev group were 4.75%, 3.38%, and 0.88%, respectively, for normal microbial cultivation. There was no significant difference in bacterial contamination among the three groups with times (P = .502). Bacterial contamination of the 20% S + Lev group showed a significant difference in comparison with the 20% S or 20% S + Dex group (P < .05) in two culture methods; however, no significant difference was found between the 20% S and 20% S + Dex group (P = .208). There were two samples positive for fungi in the 20% S and 20% S + Dex group and three samples in the 20% S + Lev group in normal cultivation during 28 days. None of the samples was positive with fungi in airtight cultivation on the 28th day. There was also less bacterial contamination in airtight cultivation than in normal cultivation for the three groups on the 28th day. Conclusions: Our study shows that 20% autologous serum drops can be safely prepared and stored at 4°C in an open system under a strict protocol for at least 28 days, and antimicrobial agents could reduce the risk of contamination.
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Affiliation(s)
- Yuqiong Yang
- Department of Ophthalmology, Daping Hospital, Army Medical University , Chongqing, China
| | - Xiaoyan Zhu
- Department of Ophthalmology, Guizhou Provincial People's Hospital , Guizhou, China
| | - Jun Yang
- Department of Gastroenterology, People's Hospital of Chongqing Banan District , Chongqing, China
| | - Anjie Shi
- Department of Ophthalmology, Daping Hospital, Army Medical University , Chongqing, China
| | - Meng Jiang
- Department of Technology, Southwest Pharmaceutical Co. Ltd , Chongqing, China
| | - Yue Peng
- Department of Technology, Southwest Pharmaceutical Co. Ltd , Chongqing, China
| | - Min Li
- Clinical Laboratory, Daping Hospital, Army Medical University , Chongqing, China
| | - Yaling Wang
- Department of Nursing, Daping Hospital,Army Medical University , Chongqing, China
| | - Hongfeng Yuan
- Department of Ophthalmology, Daping Hospital, Army Medical University , Chongqing, China
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García-Martín E, Pernía-López S, Romero Jiménez RM, García-Valcárcel B, Martínez-Ortega PA, Sanjurjo-Saez M. The use of autologous serum eye drops for the treatment of ocular surface disorders. Eur J Hosp Pharm 2019; 26:314-317. [PMID: 31798853 DOI: 10.1136/ejhpharm-2018-001527] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2018] [Revised: 04/04/2018] [Accepted: 04/15/2018] [Indexed: 11/04/2022] Open
Abstract
Objectives To investigate the use of autologous serum (AS) eye drops in patients with ocular surface disorders who were refractory to conventional treatments. Methods A retrospective cohort study was conducted at a tertiary care centre. We included patients with a prescription of AS eye drops from December 2006 to January 2016. Electronic prescriptions (Prescriplant) and clinical histories were reviewed. A database with sociodemographic and pharmacotherapheutic variables was created. The efficacy was evaluated subjectively and adverse effects was a measurement of safety. AS eye drops were elaborated, in a laminar flow hood, with the blood samples for a final concentration of 20%. Results One hundred and seventy-three patients were considered for the study, 78.03% of them female. Their mean age was 63.87 years (SD 16.69). The use of AS eye drops was indicated for several diseases: corneal diseases (corneal ulcer or corneal persistent epithelial defects) (34.32%); Sjögren syndrome (17.16%); dry eye resulting from autoimmune disease (15.38%); and blepharitis/blepharospasm (12.43%). The regular dosage was every 3 or 4 hours (40.46%). 21.97% patients used the AS in one eye only. The mean length of treatment was 2.71 years. All patients, except one, improved their symptoms with the treatment and no one suffered harmful effects. Conclusions Numerous national and international guidelines on dry eye treatment have been published, but they differ in dosing, concentration and indication of AS eye drops. Consequently, there is no consensus about the best therapy with AS. In this article we describe the clinical practice of AS eye drops. In the study, indications for AS therapy were mostly: corneal diseases; Sjögren syndrome; and dry eye resulting from autoimmune disease; and blepharitis or blepharospasm. Patients went to the hospital pharmacy to pick up AS eye drops before 90 days, it ensures the stability of eye drops. AS is an effective, safe and well tolerated treatment.
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Affiliation(s)
- Estela García-Martín
- Pharmacy Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Sagrario Pernía-López
- Pharmacy Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - R M Romero Jiménez
- Pharmacy Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Blanca García-Valcárcel
- Ophthalmology Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Pilar A Martínez-Ortega
- Pharmacy Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - María Sanjurjo-Saez
- Pharmacy Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
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Yoon CH, Lee HJ, Park HY, Kim H, Kim MK, Jeoung JW, Oh JY. Effects of topical autologous serum on the ocular surface in patients with toxic corneal epitheliopathy induced by anti-glaucoma drugs. Int Ophthalmol 2019; 40:547-552. [PMID: 31705358 DOI: 10.1007/s10792-019-01211-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2019] [Accepted: 10/28/2019] [Indexed: 01/29/2023]
Abstract
PURPOSE To investigate the effects of topical autologous serum application on the ocular surface in patients with toxic corneal epitheliopathy induced by anti-glaucoma drugs. METHODS The patients who had corneal epitheliopathy because of preservative-containing anti-glaucoma eye drops were prospectively enrolled. The epitheliopathy was refractory to preservative-free artificial tear treatment. The patients topically applied 20% autologous serum to the eye eight times per day for 1 month. Baseline and one-month change in symptoms and signs were assessed by the Ocular Surface Disease Index (OSDI) questionnaire, tear film break-up time (TFBUT), Schirmer I values, corneoconjunctival staining scores, corneal sensitivity, InflammaDry® tear immunoassay, and tear cytokine profiles using a bead-based multiplex assay. RESULTS A total of ten consecutive patients were enrolled between January and August 2018 and evaluated after one-month treatment with 20% autologous serum eye drops. Significant improvement was observed in symptoms (OSDI scores from 25.5 ± 20.9 to 10.5 ± 12.0; P = .039), TFBUT (from 3.1 ± 1.8 s to 5.4 ± 2.3 s; P = .025), corneoconjunctival staining scores (from 7.7 ± 1.8 to 1.8 ± 1.9 NEI scale; P = .005), corneal sensitivity (from 4.6 ± .9 cm to 5.8 ± .5 cm; P = .013), and metalloproteinase-9 levels (P = .013). There were no significant changes in Schirmer I values and tear cytokine levels on multiplex assays. Treatment-related side effects were not detected. CONCLUSIONS Topical instillation of 20% autologous serum is an effective treatment for toxic corneal epitheliopathy associated with anti-glaucoma eye drops. TRIAL REGISTRATION NUMBER KCT0003827.
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Affiliation(s)
- Chang Ho Yoon
- Department of Ophthalmology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.,Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Hyun Ju Lee
- Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Hye Youn Park
- Tissue Bank, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Hyungsuk Kim
- Department of Laboratory Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Mee Kum Kim
- Department of Ophthalmology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.,Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Jin Wook Jeoung
- Department of Ophthalmology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Joo Youn Oh
- Department of Ophthalmology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea. .,Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
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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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Bernabei F, Roda M, Buzzi M, Pellegrini M, Giannaccare G, Versura P. Blood-Based Treatments for Severe Dry Eye Disease: The Need of a Consensus. J Clin Med 2019; 8:E1478. [PMID: 31533289 PMCID: PMC6780616 DOI: 10.3390/jcm8091478] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Revised: 09/05/2019] [Accepted: 09/12/2019] [Indexed: 01/08/2023] Open
Abstract
The use of blood-based eye drops as therapy for various diseases of the ocular surface has become increasingly popular in ophthalmic practice during recent years. The rationale for their use is based on the promotion of cellular proliferation and migration thanks to the supply of metabolically active substances, in particular growth factors. Blood-derived eye drops have been used for the treatment of several ocular surface disorders, such as dry eye disease, corneal ulcer, persistent epithelial defect, neurotrophic keratitis, ocular surface burn, recurrent corneal erosion, and limbal stem-cell deficiency. Both autologous (from patients themselves) and heterologous (from adult donors or from cord blood sampled at birth)-derived products exist, and each source has specific pros and cons. Despite an extensive literature, several issues are still under debate and the aim of this manuscript is to review the indications, preparation methods and storage, characterization of content, rationale for clinical outcomes, patient stratification, length of treatment, and rationale for repeated treatments at disease relapse. A rationale based on a "5 Ws and 2 Hs" protocol is proposed as a way of thinking, with the attempt to clarify Who, Why, When, Where, What, and How to use these treatment options.
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Affiliation(s)
- Federico Bernabei
- Ophthalmology Unit, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum University of Bologna, S.Orsola-Malpighi Teaching Hospital, 40138 Bologna, Italy.
| | - Matilde Roda
- Ophthalmology Unit, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum University of Bologna, S.Orsola-Malpighi Teaching Hospital, 40138 Bologna, Italy.
| | - Marina Buzzi
- Emilia Romagna Cord Blood Bank-Transfusion Service, S.Orsola-Malpighi Teaching Hospital, 40138 Bologna, Italy.
| | - Marco Pellegrini
- Ophthalmology Unit, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum University of Bologna, S.Orsola-Malpighi Teaching Hospital, 40138 Bologna, Italy.
| | - Giuseppe Giannaccare
- Department of Ophthalmology, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy.
| | - Piera Versura
- Ophthalmology Unit, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum University of Bologna, S.Orsola-Malpighi Teaching Hospital, 40138 Bologna, Italy.
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Abstract
PURPOSE OF REVIEW The prevalence and burden of dry eye disease continues to grow at a rapid pace, creating an increased need for new therapies. In a sector once limited to only a handful of treatments, clinicians now have multiple options available for patients who fail traditional therapies. This review summarizes the various treatment options available to clinicians treating complex dry eye disease patients. RECENT FINDINGS As we better understand the multifactorial mechanisms leading to dry eye disease, treatments increasingly focus on the amelioration of the underlying deficiencies and inflammation, rather than on transient symptomatic relief alone. Most topical medications seek to replace deficient growth factors and/or decrease inflammation on the ocular surface. The majority of new devices and procedures seek to treat meibomian gland dysfunction, with one new device stimulating tear production through utilizing the nasolacrimal reflex pathway. SUMMARY Clinicians have more options at their disposal in the treatment of dry eye disease than ever before, including topical medications and devices.
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Qi J, Hu X, Dong X, Lu Y, Lu H, Zhao W, Wu W. Towards more accurate bioimaging of drug nanocarriers: turning aggregation-caused quenching into a useful tool. Adv Drug Deliv Rev 2019; 143:206-225. [PMID: 31158405 DOI: 10.1016/j.addr.2019.05.009] [Citation(s) in RCA: 175] [Impact Index Per Article: 29.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2018] [Revised: 05/04/2019] [Accepted: 05/29/2019] [Indexed: 01/12/2023]
Abstract
One of the current challenges in the monitoring of drug nanocarriers lies in the difficulties in discriminating the carrier-bound signals from the bulk signals of probes. Environment-responsive probes that enable signal switching are making steps towards a solution to this problem. Aggregation-caused quenching (ACQ), a phenomenon generally regarded as unfavorable in bioimaging, has turned out to be a promising characteristic for achieving environment-responsiveness and eliminating free-probe interference. So-called ACQ probes emit fluorescence when dispersed molecularly within the carrier matrix but quench immediately and absolutely once they are released into the ambient aqueous environment upon the degradation of the nanocarriers. Therefore, the fluorescence observed represents integral nanocarriers. Based on this rationale, the in vivo fates of various nanocarriers have been explored using live imaging equipment, with very interesting findings revealing the role of the particles. The current applications are however restricted to nanocarriers with highly hydrophobic matrices (lipid or polyester nanoparticles) or with a hydrophobic core-hydrophilic shell structure (micelles). The ACQ-based bioimaging strategy is emerging as a promising tool to achieve more accurate bioimaging of drug nanocarriers. This review article provides an overview of the ACQ phenomenon and the rationale for and examples of applications, as well as the limitations of the ACQ-based strategy, with a focus on improving the accuracy of bioimaging of nanoparticles.
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Marchand M, Harissi-Dagher M, Germain M, Thompson P, Robert MC. Serum drops for ocular surface disease: national survey of Canadian cornea specialists. Can J Ophthalmol 2018; 53:266-271. [DOI: 10.1016/j.jcjo.2017.09.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2017] [Revised: 08/04/2017] [Accepted: 09/05/2017] [Indexed: 10/18/2022]
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Ali TK, Gibbons A, Cartes C, Zarei-Ghanavati S, Gomaa M, Gonzalez I, Gonzalez AE, Ozturk HE, Betancurt C, Perez VL. Use of Autologous Serum Tears for the Treatment of Ocular Surface Disease From Patients With Systemic Autoimmune Diseases. Am J Ophthalmol 2018; 189:65-70. [PMID: 29470971 DOI: 10.1016/j.ajo.2018.02.009] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2017] [Revised: 01/22/2018] [Accepted: 02/11/2018] [Indexed: 10/18/2022]
Abstract
PURPOSE To describe the safety and efficacy of autologous serum tears (AST) in managing ocular surface disease resistant to conventional therapy in patients with systemic autoimmune disease(s). DESIGN Retrospective, interventional case series. METHODS Records of patients from 2009 to 2015 with systemic autoimmune disease treated with AST (20%-50%) for chronic surface disease were analyzed. Standardized measures of subjective dry eye symptoms, objective dry eye staining of the cornea, and slit-lamp findings including punctate epithelial erosion (PEE), filamentary keratopathy (FK), and corneal epithelial defects (KED) were compared during first and last visit. We attempted to standardize outcomes by creating a scale from 1 to 4 for subjective and objective components: worsening (1), no improvement (2), partial improvement (3), and complete resolution (4). RESULTS Fifty-one patients (101 eyes) were included. The mean age was 59.8 ± 13.2 years (72.5% female). Average use of AST was 14.3 ± 11.7 months. Complete objective improvement of initial slit-lamp findings was achieved in 30% and partial improvement in 55% of eyes. Presence of PEE, FK, and KED decreased from 92.1% to 52.5% (P < .001), from 22.8% to 9.9% (P = .02), and from 5% to 2% (P = .44) of the eyes, respectively. Full subjective improvement of symptoms was achieved in 34.6%, partial in 50.5%, and none in 14.9% of patients. No adverse side effects were noted during follow-up. CONCLUSIONS AST are a safe and effective adjunct therapy in improving both objective signs and subjective symptoms of ocular surface disorders associated with systemic autoimmune disease(s).
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Abstract
PURPOSE OF REVIEW This review aims to describe the recent findings on epidemiology, pathophysiology, and management of neuropathic symptoms of the ocular surface, with a focus on potential similarities between sensations of dry eye, pain and itch. RECENT FINDINGS A narrative review of the literature was undertaken. Key references from research in dry eye, neuropathic symptoms of the ocular surface, ocular pain and itch, as well as general references on itch and pain neurobiology were included. Recent findings suggest aspects of dry eye, chronic ocular pain and itch symptomatology are driven by neuropathic pain mechanisms involving peripheral and central sensitization processes. SUMMARY Ocular dryness, pain, and itch are prevalent complaints with several of shared features. Multiple lines of evidence suggest that peripheral and central neuronal sensitization processes are involved in generating and maintaining ocular sensory symptoms. Research is warranted on the epidemiology of ocular sensations, molecular mechanisms involved in nociception and pruriception in the eye, electrophysiological alterations in animal models of eye conditions, and therapeutic modalities that can alleviate unpleasant ocular sensations.
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Beylerian M, Lazaro M, Magalon J, Veran J, Darque A, Grimaud F, Stolowy N, Beylerian H, Sabatier F, Hoffart L. [Autologous serum tears: Long-term treatment in dry eye syndrome]. J Fr Ophtalmol 2018; 41:246-254. [PMID: 29602451 DOI: 10.1016/j.jfo.2017.11.008] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2017] [Revised: 11/11/2017] [Accepted: 11/17/2017] [Indexed: 10/17/2022]
Abstract
INTRODUCTION Dry eye disease is a multifactorial pathology of the ocular surface. The high incidence of this pathology, as well as its significant impact on quality of life and vision and its financial cost, makes it a real public health problem. While the treatment of mild cases is generally simple and effective, treatment of severe forms is often disappointing. The use of autologous serum tears (AST) represents a therapeutic alternative for the most severe cases. The purpose of our study is to evaluate the efficacy of long-term AST treatment in patients with severe dry eye disease refractory to conventional treatment or secondary to systemic diseases such as Sjögren's syndrome or Graft versus Host disease (GVH), or ocular pathologies such as neurotrophic keratitis, chemical burns and ocular cicatricial pemphigoid. PATIENTS AND METHODS This is a monocentric retrospective observational study conducted on 47 patients, with 83 eyes treated with autologous serum eye drops for isolated or secondary dry eye disease at the Marseille Public Hospitals between April 2014 and April 2017. The patients' subjective symptoms (ocular surface disease index [OSDI] score), their degree of satisfaction and the side effects were collected using questionnaires. Tear Break Up Time (BUT) and Schirmer scores were noted. A clinical evaluation based on fluorescein staining (Oxford score) was carried out prior to treatment with AST at P0 followed by 5 periods: P1 (between 1 and 3 months), P2 (3 to 9 months), P3 (9 to 15 months), P4 (15 months to 24 months), and P5 (>24 months). RESULTS Out of the 83 eyes treated, the mean age was 54.39±21.56. There were 20 males (42.55 %) and 27 females (57.44 %); treatment indications consisted mainly of 25.53 % GVH, 21.27 % severe dry eye disease and 19.14 % Sjögren syndrome. The mean duration of follow-up was 9.82 months±15.50. The OSDI score decreased by 19.32 points±29.37 (P<0.05) between P0 and P1 and by 23.06 points±18.41 (P<0.05) between P0 and P4. The Oxford clinical score showed a significant decrease by the third month of treatment, between P0 and P2, by 1.32 points±1.76 (P<0.05). The Schirmer test and the BUT also showed an improvement in dry eye symptoms over time with AST, significantly at P1 (P<0.05). DISCUSSION Complementary biological analyzes on the composition of AST are under way in order to identify predictive factors of effectiveness; patients not responding to AST treatment might respond to allogeneic serum from healthy donor cord blood. CONCLUSION On this first series of 83 eyes treated with ASD, clinical efficacy was noted in most of the patients. No infectious complications were reported, and the satisfaction rate was very high.
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Affiliation(s)
- M Beylerian
- Service d'ophtalmologie, CHU de Hôpital La Timone, 264, rue Saint-Pierre, 13385 Marseille, France.
| | - M Lazaro
- Pharmacie, CHU Hôpital La Conception, 13005 Marseille, France
| | - J Magalon
- Laboratoire de cultures et de thérapies cellulaires (LCTC), CHU de La Conception, 13005 Marseille, France
| | - J Veran
- Laboratoire de cultures et de thérapies cellulaires (LCTC), CHU de La Conception, 13005 Marseille, France
| | - A Darque
- Pharmacie, CHU Hôpital La Conception, 13005 Marseille, France
| | - F Grimaud
- Pharmacie, CHU Hôpital La Conception, 13005 Marseille, France
| | - N Stolowy
- Service d'ophtalmologie, CHU de Hôpital La Timone, 264, rue Saint-Pierre, 13385 Marseille, France
| | - H Beylerian
- Service d'ophtalmologie, CHU hôpital Gui-De-Chauliac, 34000 Montpellier, France
| | - F Sabatier
- Laboratoire de cultures et de thérapies cellulaires (LCTC), CHU de La Conception, 13005 Marseille, France
| | - L Hoffart
- Service d'ophtalmologie, CHU de Hôpital La Timone, 264, rue Saint-Pierre, 13385 Marseille, France
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The corneal epitheliotrophic abilities of lyophilized powder form human platelet lysates. PLoS One 2018; 13:e0194345. [PMID: 29547658 PMCID: PMC5856377 DOI: 10.1371/journal.pone.0194345] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2017] [Accepted: 03/01/2018] [Indexed: 12/20/2022] Open
Abstract
Purpose To evaluate whether lyophilized human platelet lysate (HPL) powder can preserve the growth factor concentrations and epitheliotrophic properties of liquid HPL, and potentially be used as a clinically-friendly treatment option. Methods Two commercialized liquid HPLs, UltraGRO TM (Helios, Atlanta, GA) and PLTMax (Mill Creek, Rochester, MI), were obtained and converted to lyophilized powder. After redissolution, lyophilized powder HPLs were compared with liquid HPLs, as well as human peripheral serum (HPS) and fetal bovine serum (FBS) in liquid or redissolved lyophilized powder forms. Concentrations of epidermal growth factor (EGF), transforming growth factor-β1 (TGF-β1), platelet-derived growth factor-AB (PDGF-AB) and platelet-derived growth factor-BB (PDGF-BB) were evaluated by enzyme-linked immunosorbent assay (ELISA). Human corneal epithelial cell line was incubated with the blood derivatives and evaluated for cell migration with scratch-induced directional wounding and proliferation with MTS assays. Cell differentiation was examined by transepithelial electrical resistance (TEER). Fluorescein staining and in vivo confocal microscopy were used to evaluate in vivo corneal epithelial wound healing in Sprague-Dawley rats that underwent corneal debridement and topical application of liquid and redissolved powder HPLs. Results Liquid form and redissolved lyophilized powder form HPLs had similar concentrations of EGF, TGF-β1, PDGF-AB and PDGF-BB. In vitro experiments on cell migration, proliferation and differentiation and rat models on wound healing demonstrated no significant difference between the liquid and redissolved lyophilized powder forms for HPLs, HPS and FBS. In vivo confocal microscopy revealed similar wound healing process at different layers of cornea after corneal epithelial debridement between liquid form and redissolved lyophilized power form of HPLs. Conclusions The redissolved lyophilized powder form of both commercialized HPLs showed similar growth factor concentrations and corneal epitheliotrophic abilities compared to the liquid form. Results suggest that the properties of liquid HPLs can be retained despite lyophilization and that lyophilized HPLs can be a treatment option for corneal epithelial disorders.
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Drew VJ, Tseng CL, Seghatchian J, Burnouf T. Reflections on Dry Eye Syndrome Treatment: Therapeutic Role of Blood Products. Front Med (Lausanne) 2018. [PMID: 29527528 PMCID: PMC5829051 DOI: 10.3389/fmed.2018.00033] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Dry eye syndrome (DES) is a multifactorial, frequent, pathology characterized by deficient tear production or increased evaporation of tears and associated with ocular surface alteration and inflammation. It mostly affects, but not exclusively, older individuals and leads to varying degrees of discomfort and decreased quality of life. Although the typical treatments of DES rely on using artificial tears, polyunsaturated fatty acids, integrin antagonists, anti-inflammatory agents, or on performing punctal occlusion, recently, standardized blood-derived serum eye drops (SED) are generating much interest as a new physiological treatment option. The scientific rationale in using SED for treating or releasing the symptoms of DES is thought to lie in its composition in multiple factors that resembles that of tears and contributes to the healing and protection of the ocular surface. This manuscript seeks to provide relevant background information on the management of DES, and on the increasing role that various types of SED or platelet lysates, from autologous or allogeneic origins, are playing in the improved therapeutic management of this pathology. The increasing role played by blood establishments in producing better-standardized SED is also addressed.
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Affiliation(s)
- Victor J Drew
- International PhD Program of Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan.,College of Biomedical Engineering, Graduate Institute of Biomedical Materials and Tissue Engineering, Taipei Medical University, Taipei, Taiwan
| | - Ching-Li Tseng
- International PhD Program of Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan.,College of Biomedical Engineering, Graduate Institute of Biomedical Materials and Tissue Engineering, Taipei Medical University, Taipei, Taiwan
| | | | - Thierry Burnouf
- International PhD Program of Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan.,College of Biomedical Engineering, Graduate Institute of Biomedical Materials and Tissue Engineering, Taipei Medical University, Taipei, Taiwan
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Rauz S, Koay SY, Foot B, Kaye SB, Figueiredo F, Burdon MA, Dancey E, Chandrasekar A, Lomas R. The Royal College of Ophthalmologists guidelines on serum eye drops for the treatment of severe ocular surface disease: full report. Eye (Lond) 2017:eye2017209. [PMID: 29148532 DOI: 10.1038/eye.2017.209] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Affiliation(s)
- S Rauz
- Academic Unit of Ophthalmology, Institute of Inflammation and Ageing, Birmingham and Midland Eye Centre and University of Birmingham, Birmingham, UK
| | - S-Y Koay
- Royal College of Ophthalmologists, London, UK
- Moorfields Eye Hospital, London, UK
| | - B Foot
- Royal College of Ophthalmologists, London, UK
| | - S B Kaye
- Royal Liverpool University Hospital, Liverpool, UK
| | - F Figueiredo
- Newcastle Royal Victoria Infirmary, Newcastle, UK
| | - M A Burdon
- Royal College of Ophthalmologists, London, UK
- Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | - E Dancey
- Serum Eye Drops Patient Focus and Support Group, Birmingham, UK
| | | | - R Lomas
- NHS Blood and Transplant Tissue Services, Liverpool, UK
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Thulasi P, Djalilian AR. Update in Current Diagnostics and Therapeutics of Dry Eye Disease. Ophthalmology 2017; 124:S27-S33. [PMID: 29055359 PMCID: PMC6660902 DOI: 10.1016/j.ophtha.2017.07.022] [Citation(s) in RCA: 93] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2017] [Revised: 07/17/2017] [Accepted: 07/21/2017] [Indexed: 12/28/2022] Open
Abstract
Dry eye disease (DED) represents a heterogeneous group of conditions with tear film insufficiency and signs and/or symptoms of ocular surface irritation. The clinical manifestations of DED can be highly variable; hence the diagnosis is often based on a combination of symptoms, signs, and clinical tests, given that any one of these alone would miss a significant number of patients. Similarly, the treatment must often be tailored to each patient by targeting the specific mechanisms involved in his or her disease. The purpose of this review is to summarize recent advances that have allowed us to better recognize, categorize, and treat patients with DED. The most notable new diagnostic tests in DED are tear film osmolarity, inflammatory biomarkers, and meibomian gland imaging. Therapeutically, anti-inflammatory therapy, meibomian gland heating and expression, and scleral contact lenses are some of the latest options available for treating DED.
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Affiliation(s)
| | - Ali Reza Djalilian
- Department of Ophthalmology & Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, Illinois.
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35
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Dieckmann G, Goyal S, Hamrah P. Neuropathic Corneal Pain: Approaches for Management. Ophthalmology 2017; 124:S34-S47. [PMID: 29055360 DOI: 10.1016/j.ophtha.2017.08.004] [Citation(s) in RCA: 113] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2017] [Revised: 08/01/2017] [Accepted: 08/02/2017] [Indexed: 01/16/2023] Open
Abstract
Neuropathic pain is caused by a primary lesion or dysfunction of the nervous system and can occur in the cornea. However, neuropathic corneal pain (NCP) is currently an ill-defined disease. Patients with NCP are extremely challenging to manage, and evidence-based clinical recommendations for the management of patients with NCP are scarce. The objectives of this review are to provide guidelines for diagnosis and treatment of patients with NCP and to summarize current evidence-based literature in this area. We performed a systematic literature search of all relevant publications between 1966 and 2017. Treatment recommendations are, in part, based on methodologically sound randomized controlled trials (RCTs), demonstrating superiority to placebo or relevant control treatments, and on the consistency of evidence, degree of efficacy, and safety. In addition, the recommendations include our own extensive experience in the management of these patients over the past decade. A comprehensive algorithm, based on clinical evaluation and complementary tests, is presented for diagnosis and subcategorization of patients with NCP. Recommended first-line topical treatments include neuroregenerative and anti-inflammatory agents, and first-line systemic pharmacotherapy includes tricyclic antidepressants and an anticonvulsant. Second-line oral treatments recommended include an opioid-antagonist and opiate analgesics. Complementary and alternative treatments, such as cardiovascular exercise, acupuncture, omega-3 fatty acid supplementation, and gluten-free diet, may have additional benefits, as do potential noninvasive and invasive procedures in recalcitrant cases. Medication selection should be tailored on an individual basis, considering side effects, comorbidities, and levels of peripheral and centralized pain. Nevertheless, there is an urgent need for long-term studies and RCTs assessing the efficacy of treatments for NCP.
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Affiliation(s)
- Gabriela Dieckmann
- Cornea Service, New England Eye Center, Department of Ophthalmology, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts; Center for Translational Ocular Immunology, Department of Ophthalmology, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts
| | - Sunali Goyal
- Department of Ophthalmology, Jones Eye Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas
| | - Pedram Hamrah
- Cornea Service, New England Eye Center, Department of Ophthalmology, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts; Center for Translational Ocular Immunology, Department of Ophthalmology, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts.
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Treatment of Dry Eye Disease with Autologous Platelet-Rich Plasma: A Prospective, Interventional, Non-Randomized Study. Ophthalmol Ther 2017; 6:285-293. [PMID: 28791607 PMCID: PMC5693817 DOI: 10.1007/s40123-017-0100-z] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2017] [Indexed: 11/16/2022] Open
Abstract
Introduction The objective of this study was to evaluate the use of autologous platelet-rich plasma (PRP) eye drops as monotherapy for the treatment of moderate to severe cases of dry eye disease. Methods Three hundred and sixty-eight patients with moderate to severe dry eye disease (DED) were included in this prospective case series. Subjects were classified as evaporative DED (EDED) or aqueous deficient DED (ADDED). Improvement of the DED subjective symptoms, corneal fluorescein staining (CFS), and corrected distance visual acuity (BCVA) were evaluated. We also analysed how many rounds of PRP therapy were used. Results Two hundred and ninety-seven (80.7%) patients were women, and 71 (19.3%) were men. Two hundred and thirty-two (63%) patients had EDED, while 136 (37%) had ADDED. After 6 weeks of monotherapy treatment with autologous PRP, dry eye symptoms improved in 322 (87.5%) cases. A decrease of CFS was observed in 280 (76.1%) patients. One hundred and six (28.8%) patients improved at least 1 line of BCVA. The scores in the ocular Surface Disease Index and the Oxford scale of corneal fluorescein staining decreased statistically after the treatment (p < 0.05). Conclusion The topical use of autologous platelet-rich plasma as monotherapy is an effective treatment to improve signs and symptoms in patients suffering from moderate to severe chronic DED.
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Jones L, Downie LE, Korb D, Benitez-del-Castillo JM, Dana R, Deng SX, Dong PN, Geerling G, Hida RY, Liu Y, Seo KY, Tauber J, Wakamatsu TH, Xu J, Wolffsohn JS, Craig JP. TFOS DEWS II Management and Therapy Report. Ocul Surf 2017; 15:575-628. [DOI: 10.1016/j.jtos.2017.05.006] [Citation(s) in RCA: 578] [Impact Index Per Article: 72.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2017] [Accepted: 05/03/2017] [Indexed: 02/06/2023]
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Panahi Y, Rajaee SM, Sahebkar A. Ocular Effects of Sulfur Mustard and Therapeutic Approaches. J Cell Biochem 2017; 118:3549-3560. [DOI: 10.1002/jcb.25892] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2017] [Accepted: 01/18/2017] [Indexed: 01/06/2023]
Affiliation(s)
- Yunes Panahi
- Chemical Injuries Research CenterBaqiyatallah University of Medical SciencesTehranIran
| | - Seyyed Mahdi Rajaee
- Chemical Injuries Research CenterBaqiyatallah University of Medical SciencesTehranIran
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Marks DC, van der Meer PF. Serum eye drops: a survey of international production methods. Vox Sang 2017; 112:310-317. [PMID: 28332214 DOI: 10.1111/vox.12502] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2016] [Revised: 01/24/2017] [Accepted: 01/25/2017] [Indexed: 12/17/2022]
Abstract
BACKGROUND Serum eye drops (SEDs) are used to treat dry eye syndrome and non-healing corneal lesions when other treatments fail. Despite many clinical studies demonstrating the efficacy of both autologous and allogeneic SEDs, there is no internationally harmonized method for producing SEDs. MATERIALS AND METHODS A 40-question survey requesting information regarding donor selection, blood collection and processing, infectious disease screening, shelf life and regulatory requirements for the production of autologous and allogeneic SEDs was developed by the Biomedical Excellence for Safer Transfusion Collaborative. Survey data were collected into a database via a secure web interface and then downloaded into Excel for further analysis. RESULTS A total of 55 responses were received, with 21 responses from centres indicating they produce SEDs. Based on the responses, collection and processing practices differ widely, according to the size of the centre making the SEDs, and their ability to collect, process and test the blood. CONCLUSION Despite divergences in the methods for producing SEDs, the end result is a small-volume aliquot of serum that can be administered by a patient at home. If more centres move from producing autologous to allogeneic SEDs, this may provide an opportunity for production methods to become more standardized internationally.
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Affiliation(s)
- D C Marks
- Research and Development, Australian Red Cross Blood Service, Sydney, NSW, Australia
| | - P F van der Meer
- Department of Product and Process Development, Sanquin Blood Supply, Amsterdam, The Netherlands
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Huang CJ, Sun YC, Christopher K, Pai ASI, Lu CJ, Hu FR, Lin SY, Chen WL. Comparison of corneal epitheliotrophic capacities among human platelet lysates and other blood derivatives. PLoS One 2017; 12:e0171008. [PMID: 28152010 PMCID: PMC5289502 DOI: 10.1371/journal.pone.0171008] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2016] [Accepted: 01/13/2017] [Indexed: 12/20/2022] Open
Abstract
PURPOSE To evaluate the corneal epitheliotropic abilities of two commercialized human platelet lysates (HPLs) and to compare the results with other blood derivatives, including human peripheral serum (HPS) and bovine fetal serum (FBS). METHODS In vitro, human corneal epithelial cells were incubated in various concentrations (0%, 3%, 5% and 10%) of blood derivatives. Two commercialized HPLs, including UltraGRO TM (Helios, Atlanta, GA) and PLTMax (Mill Creek, Rochester, MI), were tested and compared with HPS and FBS. Scratch-induced directional wounding assay was performed to evaluate cellular migration. MTS assay was used to evaluate cellular proliferation. Cellular differentiation was examined by scanning electron microscopy, inverted microscopy and transepithelial electrical resistance. Sprague-Dawley rats were used to evaluate the effects of the blood derivatives on corneal epithelial wound healing in vivo. Different blood derivatives were applied topically every 2 hours for 2 days after corneal epithelial debridement. The concentrations of epidermal growth factor (EGF), transforming growth factor -β1 (TGF-β1), fibronectin, platelet-derived growth factor-AB (PDGF-AB), PDGF-BB, and hyaluronic acid in different blood derivatives were evaluated by enzyme-linked immunosorbent assay (ELISA). RESULTS In vitro experiments demonstrated statistically comparable epitheliotropic characteristics in cellular proliferation, migration, and differentiation for the two commercialized HPLs compared to FBS and HPS. Cells cultured without any serum were used as control group. The epitheliotropic capacities were statistically higher in the two commercialized HPLs compared to the control group (p<0.05). Among the different concentrations of blood derivatives, the preparations with 3% yielded better outcomes compared to 5% and 10%. In rats, HPLs also caused improved but not statistically significant wound healing compared to HPS. All the blood derivatives had better wound healing ratios than the control group (p<0.05). In the quantification of epitheliotropic factors, UltraGRO and PLTMax had significantly higher levels of EGF, TGF- β1, fibronectin than human peripheral serum (p<0.05). CONCLUSIONS Both commercialized HPLs showed comparable corneal epitheliotropic abilities and wound healing rates compared to HPS and FBS in the in vivo and in vitro studies. Our results suggest that HPLs may have the potential to replace HPS in the treatment of corneal epithelial problems.
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Affiliation(s)
- Chien-Jung Huang
- Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan
| | - Yi-Chen Sun
- Department of Ophthalmology, Taipei Tzu Chi General Hospital, The Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan
| | - Karen Christopher
- Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan, United States of America
| | - Amy Shih-I Pai
- Sydney Medical School, University of Sydney, Sydney, Australia
| | - Chia-Ju Lu
- Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan
| | - Fung-Rong Hu
- Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan
- Center of Corneal Tissue Engineering and Stem Cell Biology, National Taiwan University Hospital, Taipei, Taiwan
| | - Szu-Yuan Lin
- Department of Ophthalmology, Cathay General Hospital, Taipei, Taiwan
- * E-mail: (WC); (SL)
| | - Wei-Li Chen
- Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan
- Center of Corneal Tissue Engineering and Stem Cell Biology, National Taiwan University Hospital, Taipei, Taiwan
- * E-mail: (WC); (SL)
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Yılmaz U, Küçük E, Koç Ç, Gökler E. Comparison of Autologous Serum Versus Preservative Free Artificial Tear in Patients with Dry Eyes Due to Systemic Isotretinoin Therapy. Curr Eye Res 2017; 42:827-831. [PMID: 28139163 DOI: 10.1080/02713683.2016.1255758] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
PURPOSE To investigate dry eye development in the patients receiving systemic retinoic acid therapy and to compare effectiveness of Autologous Serum (AS) and preservative free artificial tear (PFAT) in the patients with dry eye disease. METHOD This prospective, crossover, double blind study was conducted on patients who have dry eyes due to systemic isotretinoin treatment for different indications. Patients detected as having dry eye during systemic isotretinoin treatment were included to our study. At baseline, 1 and 2 month of study, detailed ocular examination, best corrected visual acuity measurement, intraocular pressure measurement, and Tear Break-up Time (TBUT) and Schirmer Test (ST) without topical anesthesia were performed. We compared the efficacy of AS and PFAT. To accomplish crossover after the first month, treatment given to each patient was switched to the other treatment. Statistical analysis was measured using SPSS version 20.0. p values of < 0.05 were considered as statistically significant. RESULT At the end of the first month, there was a significant improvement for the TBUT test in both AS and PFAT groups compared to baseline (respectively p < 0.001, p < 0.001). TBUT was found to be significantly higher in the AS group compared to the PFAT group at the end of the first month (p < 0.001). At the end of the second month, TBUT was found to be significantly higher in the AS group compared to the PFAT group at the posttreatment time (p < 0.001). There was a significant OSDI score decreasing in both groups compared to that reported previously at the end of the first and second months (respectively p < 0.001, p < 0.001). OSDI score decreasing was more significant in the AS group compared to the PFAT group at both time points (respectively p < 0.001, p < 0.001). CONCLUSION AS may be an effective alternative to PFAT in the treatment of dry eye developed during isotretinoin use.
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Affiliation(s)
- Uğur Yılmaz
- a Niğde State Hospital Opthalmology Clinic , Niğde , Turkey
| | - Erkut Küçük
- a Niğde State Hospital Opthalmology Clinic , Niğde , Turkey
| | - Çağdaş Koç
- b Niğde State Hospital Dermatology Clinic , Niğde , Turkey
| | - Enes Gökler
- c Şanlıurfa Public Health Directorate , Şanlıurfa , Turkey
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Riestra AC, Alonso-Herreros JM, Merayo-Lloves J. Platelet rich plasma in ocular surface. ARCHIVOS DE LA SOCIEDAD ESPANOLA DE OFTALMOLOGIA 2016; 91:475-490. [PMID: 27062018 DOI: 10.1016/j.oftal.2016.03.001] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/05/2016] [Revised: 02/28/2016] [Accepted: 03/01/2016] [Indexed: 06/05/2023]
Abstract
The use of platelet-rich preparations has experienced a significant increase in recent years due to its role in tissue-repair and regeneration. The aim of this study is to examine the available evidence regarding the application of plasma rich in growth factors, and its variations, on the ocular surface. A review is also presented on the effects of platelet-derived growth factors, the implications of the preparation methods, and the existing literature on the safety and efficacy of these therapies in ocular surface diseases. Despite the widespread use of platelet preparations there is no consensus on the most appropriate preparation method, and growth factors concentration vary with different systems. These preparations have been used in the treatment of ocular surface diseases, such as dry eye or persistent epithelial defects, among others, with good safety and efficacy profiles, but further studies are needed to compare to the currently available alternatives.
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Affiliation(s)
- A C Riestra
- Instituto Universitario Fernández-Vega, Fundación de Investigación Oftalmológica, Universidad de Oviedo, Oviedo, España.
| | | | - J Merayo-Lloves
- Instituto Universitario Fernández-Vega, Fundación de Investigación Oftalmológica, Universidad de Oviedo, Oviedo, España
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Messmer EM, von Lindenfels V, Garbe A, Kampik A. Matrix Metalloproteinase 9 Testing in Dry Eye Disease Using a Commercially Available Point-of-Care Immunoassay. Ophthalmology 2016; 123:2300-2308. [PMID: 27665213 DOI: 10.1016/j.ophtha.2016.07.028] [Citation(s) in RCA: 100] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2016] [Revised: 07/19/2016] [Accepted: 07/20/2016] [Indexed: 11/24/2022] Open
Abstract
PURPOSE To measure matrix metalloproteinase 9 (MMP-9) in the tear film of patients with dry eye disease (DED) compared with controls and to correlate clinical findings. DESIGN In a prospective study, 101 patients and controls underwent MMP-9 testing of the tear film. Thereafter, they were evaluated for symptoms and signs of DED. PARTICIPANTS Included patients were those who showed 3 of the following 4 dry eye criteria: ocular surface disease index (OSDI) score of more than 12, tear film break-up time (TBUT) of 10 seconds or less, Schirmer test results without anesthesia of less than 10 mm/5 minutes, and corneal staining results of 1 or more. Fifty-four healthy eyes and 47 eyes fulfilling diagnostic criteria for DED of various levels of severity were included in this study. METHODS The tear film was analyzed for MMP-9 by a commercially available test (InflammaDry; Rapid Pathogen Screening, Inc, Sarasota, FL) detecting MMP-9 levels of more than 40 ng/ml. Symptoms and signs of DED were evaluated using the OSDI questionnaire, TBUT, conjunctival and corneal staining, Schirmer test results without anesthesia, and meibomian gland examination. These findings were correlated to results of the MMP-9 test in tears. MAIN OUTCOME MEASURES Positive MMP-9 results in tears. RESULTS In 19 of 47 patients confirmed with dry eye (40.4%) and in 3 of 54 controls (5.6%), the MMP-9 results were positive. This difference was statistically significant (P < 0.001). Thus, the MMP-9 results indicated a clinically significant inflammation in 40% of dry eye patients. Positive results correlated well with subjective symptoms of DED evaluated by OSDI (P = 0.001), TBUT of less than 5 seconds (P < 0.013), Schirmer test results (P < 0.001), conjunctival staining (P < 0.001), and corneal staining (P = 0.007). Moreover, MMP-9 results correlated with the number of obstructed meibomian ducts (P = 0.005) and a pathologic meibomian gland secretion (P = 0.001). The MMP-9 results were increased significantly in women (P < 0.001) and in patients with autoimmune disease (P = 0.005), especially Sjögren's syndrome (P = 0.001) and thyroid disease (P = 0.012). CONCLUSIONS Matrix metalloproteinase 9 testing in DED is a valuable new diagnostic tool. It correlated well with other dry eye tests and identified the presence of ocular surface inflammation in 40% of confirmed dry eye patients. It may be especially helpful to identify patients with ocular surface inflammation and autoimmune disease and may facilitate the decision to institute anti-inflammatory treatment in these patients.
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Affiliation(s)
- Elisabeth M Messmer
- Department of Ophthalmology, Ludwig-Maximilians-Universität, München, Germany.
| | | | - Alexandra Garbe
- Department of Ophthalmology, Ludwig-Maximilians-Universität, München, Germany
| | - Anselm Kampik
- Department of Ophthalmology, Ludwig-Maximilians-Universität, München, Germany
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Zallio F, Mazzucco L, Monaco F, Astori MR, Passera R, Drago G, Tamiazzo S, Rapetti M, Dolcino D, Guaschino R, Pini M, Ladetto M. A Single-Center Pilot Prospective Study of Topical Application of Platelet-Derived Eye Drops for Patients with Ocular Chronic Graft-versus-Host Disease. Biol Blood Marrow Transplant 2016; 22:1664-1670. [DOI: 10.1016/j.bbmt.2016.05.023] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2015] [Accepted: 05/25/2016] [Indexed: 02/05/2023]
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A Case-Control Study on the Oxidative Balance of 50% Autologous Serum Eye Drops. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2016; 2016:9780193. [PMID: 27635188 PMCID: PMC5011221 DOI: 10.1155/2016/9780193] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/03/2016] [Accepted: 07/21/2016] [Indexed: 11/17/2022]
Abstract
Importance. Autologous serum (AS) eye drops are recommended for severe dry eye in patients with ocular surface disease. No description of the antioxidant balance of AS eye drops has been reported in the literature. Objective. This study sought to evaluate the total reactive antioxidant potential (TRAP) and concentration of reactive oxygen species (ROS) in samples of 50% AS eye drops and their correlations with the demographic characteristics and lifestyle habits of patients with ocular surface disease and healthy controls. Design. This was a case-control study with a 3-month follow-up period. Participants. 16 patients with severe dry eye disease of different etiologies and 17 healthy controls matched by age, gender, and race were included. Results. TRAP and ROS were detected at all evaluated times. There were no differences in the mean ROS (p = 0.429) or TRAP (p = 0.475) levels between cases and controls. No statistically significant differences in the concentrations of ROS or TRAPs were found at 0, 15, or 30 days (p for ROS = 0.087 and p for TRAP = 0.93). Neither the demographic characteristics nor the lifestyle habits were correlated with the oxidative balance of the 50% AS eye drops. Conclusions and Relevance. Both fresh and frozen 50% AS eye drops present antioxidant capacities and ROS in an apparently stable balance. Moreover, patients with ocular surface disease and normal controls produce equivalent AS eye drops in terms of oxidative properties.
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Dry Eye Syndrome in Patients with Diabetes Mellitus: Prevalence, Etiology, and Clinical Characteristics. J Ophthalmol 2016; 2016:8201053. [PMID: 27213053 PMCID: PMC4861815 DOI: 10.1155/2016/8201053] [Citation(s) in RCA: 100] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2016] [Accepted: 03/20/2016] [Indexed: 01/13/2023] Open
Abstract
There has been substantial progress in our understanding of the ocular surface system/lacrimal function unit in the past 15 years. Keratoconjunctivitis sicca, more commonly referred to as dry eye syndrome (DES), is the most frequently encountered condition and diabetes mellitus (DM) has been identified as one of the leading causes of DES. Poor glycemic control affects both the anterior and the posterior segments of the eye and increasing prevalence of diabetes-associated DES (DMDES) has been reported in recent years. The pathogenesis and specific features of DMDES remain uncertain and interventions are limited to those used in DES. This review outlines the pathogenesis, clinical manifestations, and the current preventive and treatment strategies for diabetes-related DES.
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van der Meer PF, Seghatchian J, Marks DC. Quality standards, safety and efficacy of blood-derived serum eye drops: A review. Transfus Apher Sci 2016; 54:164-7. [PMID: 26847866 DOI: 10.1016/j.transci.2016.01.022] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
Serum eye drops (SEDs) are being used increasingly to treat dry eye syndrome and persistent corneal epithelial defects, and are usually prescribed when conventional treatments fail. SEDs are commonly sourced from the patient's own blood via an autologous collection. Although SEDs are clearly beneficial, they are not available for those patients that cannot donate sufficient blood, and some centres are moving to allogeneic SEDs. Many studies have reported that both allogeneic and autologous SEDs are effective. However, few large randomised controlled trials have been conducted to date, and clinical evidence is therefore limited to smaller studies. Alternatives to serum are also being explored, such as platelet lysate and products made from platelet rich plasma, as they are a rich source of growth factors. This article reviews how some centres are approaching allogeneic collections for SEDs, and alternatives to serum that are currently being explored.
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Affiliation(s)
- Pieter F van der Meer
- Sanquin Blood Supply, Department of Product and Process Development, Amsterdam, The Netherlands
| | - Jerard Seghatchian
- International Consultancy in Blood Components Quality/Safety Improvements, Audit/Inspection and DDR Strategies, London, UK.
| | - Denese C Marks
- The Australian Red Cross Blood Service, Sydney, Australia
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Mondy P, Brama T, Fisher J, Gemelli CN, Chee K, Keegan A, Waller D. Sustained benefits of autologous serum eye drops on self-reported ocular symptoms and vision-related quality of life in Australian patients with dry eye and corneal epithelial defects. Transfus Apher Sci 2015; 53:404-11. [DOI: 10.1016/j.transci.2015.11.011] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Abstract
PURPOSE OF REVIEW Dry eye syndrome can be difficult to manage in severe or refractory cases. In patients in whom traditional treatments have limited efficacy, alternative treatments may be considered for dry eye syndrome, including scleral lenses. The present review summarizes the evidence regarding scleral lens use in dry eye syndrome. RECENT FINDINGS Scleral lenses have become a viable option for severe dry eye syndrome, and have been shown to be efficacious and well tolerated, with most reports citing improved visual acuity and relief of symptoms. Currently, there are 18 manufacturers of scleral lenses, although published reports on scleral lenses primarily focus on the BostonSight PROSE and the Jupiter Lens. SUMMARY Scleral lenses are efficacious and well tolerated for use in severe dry eye syndrome. Further research is needed to compare different sizes and types of lenses, and to standardize outcome measures.
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