Limbitis Secondary to Autologous Serum Eye Drops in a Patient with Atopic Keratoconjunctivitis

Purpose. Report a case of limbitis secondary to autologous serum eye drops in a patient with atopic keratoconjunctivitis. Design. Interventional case report. Methods. A 32-year-old African American female with atopic keratoconjunctivitis (AKC) presented with chronic dry eye and diffuse punctate epithelial erosions refractory to conservative treatment. She was initially managed with cyclosporine ophthalmic 0.05% in addition to preservative-free artificial tears and olopatadine hydrochloride 0.2% for 6 months. She was later placed on autologous serum eye drops (ASEDs) and 4 weeks into treatment developed unilateral limbitis. The limbitis resolved shortly after stopping ASEDs in that eye; however, the drops were continued in the contralateral eye, which subsequently developed limbitis within 2 weeks. ASEDs were discontinued in both eyes, and the patient has remained quiet ever since. Results. Patient with a history of AKC and no prior history of limbitis developed limbitis shortly after starting ASEDs, which resolved promptly after discontinuation of therapy with no subsequent recurrence of inflammation. Conclusion. ASEDs are widely used in the treatment of complicated or treatment refractory dry eye. The potential side effects should be kept in mind when prescribing ASEDs for any patient, especially in those with underlying immunological diseases and circulating inflammatory factors

Neurotrophic factors and corneal nerve regeneration

The cornea has unique features that make it a useful model for regenerative medicine studies. It is an avascular, transparent, densely innervated tissue and any pathological changes can be easily detected by slit lamp examination. Corneal sensitivity is provided by the ophthalmic branch of the trigeminal nerve that elicits protective reflexes such as blinking and tearing and exerts trophic support by releasing neuromediators and growth factors. Corneal nerves are easily evaluated for both function and morphology using standard instruments such as corneal esthesiometer and in vivo confocal microscope. All local and systemic conditions that are associated with damage of the trigeminal nerve cause the development of neurotrophic keratitis, a rare degenerative disease. Neurotrophic keratitis is characterized by impairment of corneal sensitivity associated with development of persistent epithelial defects that may progress to corneal ulcer, melting and perforation. Current neurotrophic keratitis treatments aim at supporting corneal healing and preventing progression of corneal damage. Novel compounds able to stimulate corneal nerve recovery are in advanced development stage. Among them, nerve growth factor eye drops showed to be safe and effective in stimulating corneal healing and improving corneal sensitivity in patients with neurotrophic keratitis. Neurotrophic keratitis represents an useful model to evaluate in clinical practice novel neuro-regenerative drugs

Comparative study of Efficacy of Autologous Serum Ophthalmic Solution Versus Tear Substitute as Adjuvant Therapy in the Treatment of Ocular Surface Disorders

INTRODUCTION: The Ocular Surface System includes the surface and glandular epithelia of the cornea, conjunctiva, lacrimal land accessory lacrimal glands, meibomian gland, eyelashes with their associated glands of Moll and Zeis, and the nasolacrimal duct. Disruption of the function ocular surface structures may result in ocular surface disorders. Treatment for ocular surface disorders includes artificial tears substitutes, temporary or permanent punctal occlusion, bandage contact lenses, and primary treatment of adnexal diseases. Ocular surface disorder is most commonly treated with artificial tear eye substitute. Commercially available artificial tear preparation does not include essential tear components such as growth factors, vitamins, and immunoglobulins. Artificial tear substitute often contains preservatives, stabilizers, additives, which can induce toxic or allergic reactions. Recently autologous serum eye drops is routinely prescribed as an adjuvant therapy for the treatment ocular surface disorders, like dry eye disorders, neurotrophic keratitis, recurrent corneal erosion, persistent epithelial defects. Human serum apart from providing lubrication, it contains substances such as EGF, vitamin A, TGF-β, fibronectin and interleukins, which are normally found in tears. They are essential for corneal &conjunctival epithelial healing and integrity. AIM OF THE STUDY: 1. To compare the efficacy of autologous serum ophthalmic solution versus tear drops as adjuvant therapy in the treatment of ocular surface diseases. AIMS AND OBJECTIVES: PRIMARY OBJECTIVE: To compare the efficacy of autologous serum ophthalmic solution versus tear drops as adjuvant therapy in the treatment of ocular surface diseases. SECONDARY OBJECTIVE: 1. To document prevalence of ocular surface diseases. 2. To document the symptoms and clinical features of patients presented with ocular surface diseases. MATERIALS & METHODS: This prospective study was conducted at Cornea services department, RIOGOH, Madras Medical College, Egmore, Chennai-08, for a period of 6 months. Methodology: Patient presenting with ocular surface diseases to Cornea services department, RIOGOH was registered, evaluated and followed up during the study period. A detailed history of the patient was taken, General Examination and Slit lamp examination, and dilated fundus examination were done. Relevant Laboratory and Radiological imaging were done and recorded. Patients fulfilling the inclusion criteria were sub classified into one of the three following categories and given a serial number. Sub classifications for ocular surface diseases were (1) Severe dry eye, (2) Neurotrophic Ulcer and (3) Recurrent corneal erosion. Following parameters were recorded on presentation; fluorescein staining, Rose Bengal staining, Tear break up time, Schirmer’s test. Patients will be treated as per the laid down guidelines. In addition patients with odd serial number in category will be with autologous serum and patients with even serial number will be treated with tear drops. Symptom score and above mentioned parameters will be recorded during every follow-up. Treatment will be continued till symptoms disappear. PREPARATION OF SERUM: Around 30 ml of blood is extracted from patient’s vein without adding anticoagulant. The blood is kept in vertical position in tubes for about 2 hours to allow coagulation. Supernatant fluid is centrifuged to isolate the serum. 20% autologous serum is considered ideal because it contains certain growth factors at a concentration similar to that of natural tears2. Higher concentration is likely to cause irritation due to the higher viscosity. Also number of blood extraction is considerably reduced when used at lower concentration. Separated serum is labeled and preserved at 40C. Once issued, patients are advised to preserve the serum in the refrigerator at +4°C after use5. Autologous serum is protected from direct sun light to prevent degradation of some of the components like Vitamin A. SAMPLE SIZE: 30 patients. INCLUSION CRITERIA: 1. Age 15- 70 years, 2. Patients with ocular surface diseases due to; a. Severe dry eye, b. Neurotrophic ulcer, c. Recurrent corneal erosion. EXCLUSION CRITERIA: 1. Patients with Infectious blood borne diseases (HIV, HBV, HCV and Syphilis). 2. Patients with Anaemia and known blood dyscrasias. 3. Women who are pregnant or breast-feeding. 4. Patients unable to provide informed consent. CONCLUSION: Autologous serum is found to be safe and significantly effective than the artificial tear substitute in the treatment of ocular surface disorders

Soro autólogo para doenças da superfície ocular

Autologous serum has been used to treat dry eye syndrome for many years. It contains several growth factors, vitamins, fibronectin and other components that have been considered important for corneal and conjunctival integrity. Serum eye drops are usually prepared as an unpreserved blood solution. The serum is by nature well tolerated and its biochemical properties are somewhat similar to natural tears. Autologous serum eye drops have been reported to be effective for the treatment of severe dry eye-related ocular surface disorders (Sjögren's syndrome), and also other entities such as superior limbic keratoconjunctivitis, graft-versus-host disease, Stevens-Johnson syndrome, ocular cicatricial pemphigoid, recurrent or persistent corneal erosions, neurotrophic keratopathy, Mooren's ulcer, aniridic keratopathy, filtering blebs after trabeculectomy, and post-keratorefractive surgery. The purpose of this study is to review the recently published literature on ocular surface diseases treated with human autologous serum eye drops.O soro autólogo tem sido adotado como uma nova abordagem para tratar síndrome do olho seco porque contém vitaminas, alguns fatores de crecimento e fibronectina que são considerados importantes contribuintes para integridade corneana e conjuntival. Colírio de soro autólogo é produzido sem preservativo. O soro é não-alérgico e suas propriedades bioquímicas são similares à lágrima. O soro autólogo tópico tem sido relatado efetivo para o tratamento de olho seco grave relacionado a distúrbios da superfície ocular como na síndrome de Sjögren, ceratoconjuntivite límbica superior, doença do enxerto versus hospedeiro, síndrome de Stevens-Johnson, procedimentos cerato-refrativos, erosão corneana persistente ou recorrente, ceratopatia neurotrófica, úlcera de Mooren, ceratopatia associada à aniridia, e bolhas filtrantes após trabeculectomia. O objetivo do presente estudo é revisar a literatura recentemente publicada sobre doenças da superficie ocular tratadas com soro autológo tópico.The Johns Hopkins University School of Medicine Fellow in Cornea and Refractive Surgery at the Wilmer Ophthalmological InstituteUniversidade Federal de São Paulo (UNIFESP) Departamento de OftalmologiaThe Johns Hopkins University School of Medicine Wilmer Ophthalmological InstituteUNIFESP, Depto. de OftalmologiaSciEL

Regenerative Therapies in Dry Eye Disease: From Growth Factors to Cell Therapy

Dry eye syndrome is a complex and insidious pathology with a high level of prevalence among the human population and with a consequently high impact on quality of life and economic cost. Currently, its treatment is symptomatic, mainly based on the control of lubrication and inflammation, with significant limitations. Therefore, the latest research is focused on the development of new biological strategies, with the aim of regenerating affected tissues, or at least restricting the progression of the disease, reducing scar tissue, and maintaining corneal transparency. Therapies range from growth factors and cytokines to the use of different cell sources, in particular mesenchymal stem cells, due to their multipotentiality, trophic, and immunomodulatory properties. We will review the state of the art and the latest advances and results of these promising treatments in this pathology

What’s new in the field of serum-based eye drops

Worldwide serum-based eye drops are successfully used in the treatment of the Dry Eye Syndrome (DES). Autologous serum eye drops (ASEDs) are most common but allogenic eye drops were introduced in many countries mostly because of the COVID-19 pandemic. Not all aspects of the product formula have however been worked out so far. Each medical entity involved in the preparation, packaging and distribution of the product performs according to its own procedures. Various actions have therefore been undertaken to standardize, harmonize and exchange the experience in this field. In 2022 the 5th edition of EDQM’s Guide to the quality and safety of tissues and cells for human application was issued. Within the EU4Health Programme a new group for Recommendations and Guidance Documents for the Management of Substances of Human Origin (SoHO) in Hospitals is being formed. International cooperation of serumbased product users lead to the establishment of working group events — Workshops on the Eye Drops of Human Origin (EDHO) and Serum eye drop manufacturer’s group. Despite the widespread use of serum-based eye drops all over the world, in almost none of the countries, EU included, are there strict legal regulations for handling the product. It is therefore necessary to come up with a universal definition of artificial tears therapy and to determine specific procedures for the product preparation

Differential profile of protein expression on human keratocytes treated with autologous serum and plasma rich in growth factors (PRGF)

Purpose The main objective of this study is to compare the protein expression of human keratocytes treated with Plasma rich in growth factors (PRGF) or autologous serum (AS) and previously induced to myofibroblast by TGF-beta 1 treatment. Methods Blood from healthy donor was collected and processed to obtain AS and PRGF eye drops. Blood derivates were aliquoted and stored at-80 degrees C until use. Keratocyte cells were pretreated for 60 minutes with 2.5 ng/ml TGF-beta 1. After that, cells were treated with PRGF, AS or with TGF-beta 1 (control). To characterize the proteins deregulated after PRGF and AS treatment, a proteomic approach that combines 1D-SDS-PAGE approach followed by LC-MS/MS was carried out. Results Results show a catalogue of key proteins in close contact with a myofibroblastic differentiated phenotype in AS treated-cells, whereas PRGF-treated cells show attenuation on this phenotype. The number of proteins downregulated after PRGF treatment or upregulated in AS-treated cells suggest a close relationship between AS-treated cells and cytoskeletal functions. On the other hand, proteins upregulated after PRGF-treatment or downregulated in AS-treated cells reveal a greater association with processes such as protein synthesis, proliferation and cellular motility. Conclusion This proteomic analysis helps to understand the molecular events underlying AS and PRGF-driven tissue regeneration processes, providing new evidence that comes along with the modulation of TGF-beta 1 activity and the reversion of the myofibroblastic phenotype by PRGF.This study was fully supported by BTI Biotechnology Institute, a dental implant company that investigates in the fields of oral implantology and PRGF-Endoret technology. MF and FM received a salary as scientists from BTI Biotechnology Institute. EA is the Scientific Director and president of BTI Biotechnology Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Autologous blood in the management of ocular surface disorders

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

Autologous serum therapy in recalcitrant laser-assisted in situ keratomileusis-induced neurotrophic epitheliopathy

AbstractBackground/PurposeTo evaluate the efficacy of autologous serum eye drops for patients with recalcitrant laser-assisted in situ keratomileusis (LASIK)-induced neurotrophic epitheliopathy (LINE) unresponsive to conventional treatment, and to determine the possible predisposing risk factors of these patients.MethodsWe enrolled 10 consecutive patients (20 eyes) undergoing femtosecond-assisted myopic LASIK surgery presenting with recalcitrant LINE for > 1 year. Another 340 patients (713 eyes) receiving femtosecond-assisted myopic LASIK without recalcitrant LINE were set as controls. Possible risk factors associated with recalcitrant LINE were investigated. Twenty percent autologous serum treatment was prescribed to 20 eyes. The efficacy of autologous serum was assessed with ocular surface conditions, tear function, and the change of best-corrected visual acuity.ResultsAge older than 30 years [odds ratio (OR) = 7.74; 95% confidence interval (CI), 1.74–34.50], flap thickness < 110 μm (OR = 3.47; 95% CI, 1.22–9.73), and a flap diameter < 8.5 mm (OR = 5.38; 95% CI, 1.95–14.85) pose higher risks in femtosecond laser-assisted myopic LASIK. All eyes (100%) achieved remission after autologous serum treatment. The visual acuity before treatment was 0.49 ± 0.41 in LogMAR, and the visual acuity after treatment was 0.14 ± 0.22 in LogMAR. Time to achieve remission was 8.26 ± 11.87 weeks. Mean relapse-free survival after discontinuing autologous serum was 47 weeks.ConclusionRisk factors of recalcitrant LINE in femtosecond laser-assisted myopic LASIK were identified as older age, a thinner flap (<110 μm), and a small flap diameter (<8.5 mm). Autologous serum eye drops can effectively improve corneal surface conditions and postoperative visual acuity