Sjögren disease (SD) is a chronic, autoimmune disease of unknown aetiology with significant impact on quality of life. Although dryness (sicca) of the eyes and mouth are the classically described features, dryness of other mucosal surfaces and systemic manifestations are common. The key management aim should be to empower the individual to manage their condition-conserving, replacing and stimulating secretions; and preventing damage and suppressing systemic disease activity. This guideline builds on and widens the recommendations developed for the first guideline published in 2017. We have included advice on the management of children and adolescents where appropriate to provide a comprehensive guideline for UK-based rheumatology teams.

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.

The 5th CORONIS Symposium, held during the 2023 Congress of the European Association for Vision and Eye Research (EVER), highlighted the growing importance of ocular surface innervation in eye surface disorders. This article summarises the insights and perspectives shared during the symposium, which focused on the clinical relevance of ocular surface innervation, as well as on the development of innovative diagnostic and therapeutic approaches for ocular surface pathologies linked to disturbed sensory innervation. Through robust interdisciplinary collaborations, these developments hold great potential to improve patient outcomes and quality of life.

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.

Blood component therapy has shown promising potential as an emerging treatment for dry eye disease; however, it remains unclear which specific blood component is the most effective. This study aims to compare the efficacy of different blood components in the treatment of dry eye disease through a network meta-analysis, with the goal of providing the latest and most reliable evidence for clinical practice.

We conducted a systematic search of the PubMed, Web of Science, Cochrane, Embase, and Scopus databases, with the search concluding on June 1, 2024. Two independent researchers performed literature screening, data extraction, and quality assessment.

A total of 16 randomized controlled trials (RCTs) involving 898 patients with dry eye disease were included. Six different blood components were utilized in treating dry eye disease, with platelet-rich plasma (PRP) being the most widely used. The results of the network meta-analysis indicated that platelet-rich plasma eye drops (PRPD) significantly outperformed artificial tears (AT) in improving the corneal fluorescein staining score (CFSS), while autologous serum (ALS) and umbilical cord serum (UCS) also demonstrated significantly better effects than AT in enhancing tear break-up time (TBUT). Additionally, ALS, PRP injection (PRPI), and PRPD showed significantly superior outcomes compared to AT in improving the ocular surface disease index (OSDI). However, no statistically significant differences were found among the various treatment modalities regarding their effects on Schirmer's I value, CFSS, TBUT, and OSDI. SUCRA analysis predicted that UCS was the most effective in improving Schirmer's I value and TBUT, while PRP excelled in enhancing CFSS and OSDI. Limitations such as publication bias and issues related to randomization, allocation concealment, and blinding may affect the reliability of the current findings.

Blood component therapy can significantly improve the pathological damage and ocular surface health in patients with dry eye disease. For those with aqueous-deficient dry eye, UCS may represent the optimal treatment option. In contrast, for patients with more severe corneal epithelial damage, PRP may offer a more effective therapeutic approach.

https://www.crd.york.ac.uk/PROSPERO/, CRD42024534091.

Dry eye disease (DED) is a prevalent ocular condition that significantly impacts quality of life. Umbilical cord serum (UCS) has emerged as a promising therapeutic option, but its efficacy requires further investigation. This systemic review and meta-analysis aimed to evaluate the therapeutic effects of UCS eye drops in the treatment of DED.

A comprehensive literature search was conducted across multiple databases, including PubMed, Web of science, Embase, Science Direct, Cochrane Library, and China National Knowledge Network, to identify relevant clinical trials. The efficacy of UCS was assessed based on key outcome measures, such as the ocular surface disease index (OSDI), tear break-up time (TBUT), Schirmer I test, and corneal fluorescein staining scores. Meta-analyses were performed to pool the results, and the findings were presented in a forest plot.

Eight studies were included in the meta-analysis, with two relevant randomized controlled trials (RCTs) involving a total of 204 patients. Most of the included studies had a follow-up time of less than 2 months. The pooled results showed that UCS treatment significantly improved the OSDI, with a mean difference (MD) of -9.16 (95% confidence interval [CI], -12.0, -6.36) compared to baseline. Additionally, the TBUT values were higher in the UCS group, with an MD of 2.65 (95% CI, 0.93, 4.36). The Schirmer I test results showed an improvement, with an MD of 1.18 (95% CI, 0.30, 2.06). The fluorescein staining score were also lower in the UCS treatment group, with an MD of -4.71 (95% CI, -5.72, -3.69).

This meta-analysis suggested that UCS eye drops had a beneficial therapeutic effect on DED, significantly improving the OSDI, TBUT, Schirmer I test, and corneal fluorescein staining scores. However, larger RCTs with longer follow-up periods were needed to further evaluate the long-term efficacy and safety of UCS in the management of DED.

Sjögren's syndrome (SS) may cause severe dry eye symptoms. One of the therapeutic option known for almost 40 years are autologous serum eye drops (ASEDs). Due to the presence of many pro-inflammatory factors in the autologous serum of SS patients, the use of allogeneic serum is often considered a better option. In our facility almost one-fifth of the patients using allogeneic serum-based eye drops (alloSEDs) suffered from autoimmune diseases, including SS. The study aim was to compare the effectiveness of both ASEDs and alloSEDs in SS patients.

From the group of SS patients using alloSEDs, five female SS patients aged 39-73 years were selected. They had the longest history of the use of the product. The analysis was based on OSDI forms and internal questionnaires which compared the effects of ASEDs and alloSEDs application. The patients used alloSEDs for a period of 5-28 months. All had previously used ASEDs for at least 2 years.

For all five patients the mean OSDI after application of ASEDs and before introducing alloSEDs was 68.71, while the mean OSDI after the use of alloSEDs was 30.49.

In SS the treatment results are better with alloSEDs than with ASEDs. Almost all SS patients who applied both autologous and allogeneic drops reported better effects with the latter as also confirmed by the study cases.

The Institute of Hematology and Transfusion Medicine (IHTM) in Warsaw has produced autologous serum eye drops (ASEDs) for the treatment of Dry Eye Syndrome (DES) since 1991. In 2019, IHTM introduced allogeneic tears (alloSEDs) for patients on long-term treatment.

114 patients who applied alloSEDs were included in the study.They were asked to complete the OSDI questionnaire before and after using ASEDs and 100 units of alloSEDs drops from each donation. The OSDI index rates DES severity (0 no symptoms; 100 severe). We also compared the content of IL-1β, IL-2, IL- 6, IL-10 and VEGF in ASEDs (38 samples) and alloSEDs (15 serum samples). The study data covered the 2019-2022 period.

114 patients participated in the study. We compared the the effectiveness of ASEDs and alloSEDs. The average, OSDI dropped from 68.42 ± 5,86 (before application) to 51.05 ± 19,06 (after application). Data from the questionnaires (prepared at IHTM) completed and returned (41/114) present the most common indications for the use of serum drops, including DES with no underlying disease, DES secondary to GvHD (Graft versus Host Disease), Sjögren's Syndrome (SS). The study reported higher cytokine levels associated with disease entities such as SS. After application of drops with high cytokine levels, patients reported adverse reactions such as sand under the eyelids, impaired visual acuity, and worse eye lubrication.

AlloSEDs with acceptably low values of pro-inflammatory cytokines and sufficiently high levels of VEGF growth factor may contribute to alleviation of inflammatory eye symptoms.

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.

Dry eye disease (DED) is a prevalent ocular surface disease that is conventionally characterized by tear film hyperosmolarity and instability. This review presents a summarized classification of DED, followed by a comprehensive discussion of the most recent topical and systemic medications and clinical recommendations for selecting the most appropriate option for each patient.

An extensive literature search was conducted on electronic databases, such as PubMed, Scopus, and Web of Science, using keywords including "dry eye syndrome," "ocular surface disease," "medical management," "artificial tears," "topical immunomodulators," and "meibomian gland dysfunction."

The underlying reasons for DED can range from insufficient aqueous tear production to increased tear evaporation. Recent literature has provided a more in-depth understanding of the pathophysiology of DED by examining the tear film's lipid, aqueous, and mucin layers. However, despite these advancements, medical management of patients with symptomatic DED has not fully reflected this modernized knowledge of its pathophysiology.

To develop a rationalized strategy for treating DED, it is crucial to have updated knowledge of therapeutic options, their mechanisms of actions, and indications based on the DED type and underlying causes.

Serum eye drops (SED) are used to treat ocular surface disease. Reactions to SED are poorly documented.

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.

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.

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.

Although the ultimate goal of dry eye disease (DED) management is to restore the ocular surface and tear film homeostasis and address any accompanying symptoms, addressing this is not an easy task. Despite the wide range of current treatment modalities targeting multiple aspects of DED, the available DED management literature is quite heterogeneous, rendering evaluation or comparison of treatment outcomes hard or almost impossible. There is still a shortage of well-designed, large-scale, nonsponsored, randomized, controlled trials (RCTs) evaluating long-term safety and efficacy of many targeted therapies individually or used in combination, in the treatment of identified subgroups of patients with DED. This review focuses on the treatment modalities in DED management and aims to reveal the current evidence available as deduced from the outcomes of RCTs.

Allogeneic serum from blood donors is starting to be used to treat patients with dry eye disease (DED). However, the optimal dose is not known. We therefore aimed to evaluate the clinical efficaciousness and user-friendliness of micro-sized versus conventional-sized allogeneic serum eye drops (SEDs).

In a randomized trial, patients with DED first receive micro-sized SEDs (7 µl/unit) for 1 month, followed by a 1-month washout, before receiving conventional-sized SEDs (50 µl/unit) for 1 month; or vice versa. The primary endpoint was the Ocular Surface Disease Index (OSDI) score. Secondary endpoints were tear break-up time (TBT), tear production (TP), and presence of corneal punctate lesions (CP). The user-friendliness of both application systems was also compared. A linear mixed model for cross-over design was applied to compare both treatments.

Forty-nine patients completed the trial. The mean OSDI score significantly improved from 52 ± 3 to 41 ± 3 for micro-sized SEDs, and from 54 ± 3 to 45 ± 3 for conventional-sized SEDs. Non-inferiority (margin = 6) of micro-sized SEDs was established. We demonstrate a significant improvement for TBT in case of conventional-sized SEDs and for CP in both treatment groups. TP trended towards an improvement in both treatment groups. The user-friendliness of the conventional drop system was significantly higher.

For the first time, non-inferiority of micro-sized allogeneic SEDs was established. The beneficial effect of both SED volumes was similar as measured by the OSDI score. Although user-friendliness of the micro drop system was significantly lower, it is an attractive alternative as it saves valuable donor serum.

ClinicalTrials.gov (NCT03539159).

This review provides an overview of pharmacologic treatments for dry eye disease (DED), with a focus on newer developments.

Along with the existing treatments, there are several new pharmacologic treatments available and being developed for DED.

There are many currently available options for treatment of DED, and ongoing research and development to expand potential treatments for patients with DED.

Serum eye drops (SED) are an effective treatment for dry eye syndrome. However, autologous serum collection can have challenges. Patient-tailored (allogeneic) SED (PT-SED) can be made from healthy blood donors. Australian Red Cross Lifeblood has manufactured both autologous SED (Auto-SED) and PT-SED and, in May 2021, introduced Meise vial packaging. This study aimed to explore SED patient-reported outcomes and vial packaging satisfaction.

A prospective cohort study was conducted with recruitment between 1 November 2021 and 30 June 2022. Participants completed the dry eye questionnaire (DEQ5), health-related quality-of-life (SF-8™), functional assessment of chronic illness therapy-treatment satisfaction-general (FACIT-TS-G), and general wellbeing surveys. Existing patients completed these once, and new patients were surveyed at baseline, 3 months post-treatment, and 6 months post-treatment.

Participants who completed all study requirements were 24 existing and 40 new Auto-SED and 10 existing and 8 new PT-SED patients. Auto-SED patients were younger [56.2 (±14.7) years] than PT-SED patients [71.4 (±10.0) years]. Participants used a mean of 1.8 (±1.1) SED, 5.3 (±2.9) times per day. In new patients, DEQ5 scores improved within 6 months from 14.0 (±2.9) to 10.6 (±3.4) for Auto-SED and from 12.9 (±3.7) to 11.4 (±2.8) for PT-SED. General wellbeing measures improved in the new Auto-SED from 7.0 (±1.9) to 7.8 (±1.7) but were reduced for new PT-SED from 6.7 (±2.9) to 6.1 (±2.9).

SED improved dry eye symptoms in most patients, regardless of the serum source. Patients using PT-SED showed decreases in some quality-of-life measures; however, recruitment was reduced due to operational constraints, and concurrent comorbidities were not assessed. General feedback for SED and vial packaging was positive, with some improvements identified.

Serum eye drops (SEDs) are used to treat ocular surface disease (OSD) and to promote ocular surface renewal. However, their use and production are not standardized, and several new forms of human eye drops have been developed.

The International Society for Blood Transfusion Working Party (ISBT WP) for Cellular Therapies held a workshop to review the current types of eye drops of human origin (EDHO) status and provide guidance.

The ISBT WP for Cellular Therapies introduced the new terminology 'EDHO' to emphasize that these products are analogous to 'medical products of human origin'. This concept encompasses their source (serum, platelet lysate, and cord blood) and the increasingly diverse spectrum of clinical usage in ophthalmology and the need for traceability. The workshop identified the wide variability in EDHO manufacturing, lack of harmonized quality and production standards, distribution issues, reimbursement schemes and regulations. EDHO use and efficacy is established for the treatment of OSD, especially for those refractory to conventional treatments.

Production and distribution of single-donor donations are cumbersome and complex. The workshop participants agreed that allogeneic EDHO have advantages over autologous EDHO although more data on clinical efficacy and safety are needed. Allogeneic EDHOs enable more efficient production and, when pooled, can provide enhanced standardization for clinical consistency, provided optimal margin of virus safety is ensured. Newer products, including platelet-lysate- and cord-blood-derived EDHO, show promise and benefits over SED, but their safety and efficacy are yet to be fully established. This workshop highlighted the need for harmonization of EDHO standards and guidelines.

The Blood Donation Service West serves North Rhine-Westphalia (NRW), Rhineland-Palatinate (RP), and Saarland, an area of 56,500 km². In addition to routine red blood cell concentrates, plasma, and platelets, special products are provided. Since 2014, this has included autologous serum eye drops (ASED) for topical use in patients suffering from different illnesses accompanied by dry eye disease.

A volume of 250-525 mL of patient blood was collected into an anticoagulant-free blood bag. Laboratory testing included Hepatitis B/C-, HIV 1/2-, and Lues-serology. Coagulation and centrifugation were followed by leukoreduction. Single-use vials were obtained by filling mini-bag systems using a sterile tube welder. Storage at ≤-20 °C enabled a shelf-life of up to 6 months and 30 days at 4 °C after thawing for shipment.

Contracts were closed with 15 ophthalmology clinics and medical practices in NRW and RP to supply patients with ASED. The patient pool increased from 19 in 2014 to 46 in 2020, with an average age of 43-55 years. Overall, blood collections almost tripled from 31 to 100 per year, increasing the stock of deliverable single-use vials from 3328 to 13,358. Delivery in a liquid state allowed engagement of 44 pharmacies located in the patient neighborhoods for continuous supply.

Manufacturing in a closed bag system allowed integration into blood bank operations. However, cost-coverage by health insurance remained a case-by-case decision. Allogeneic application as 'just-another-blood-product' could be an aspiration. Yet, conclusive data from large clinical trials are needed for licensed provision in Germany.

Ocular surface disease is a prevalent, diverse group of conditions that cause patient discomfort and decreased visual acuity and present considerable expense to both patients and healthcare systems. Autologous serum eye drops are a topical treatment modality derived from the patient's own blood. Use of serum eye drops for ocular surface disease has been promising due to biochemical similarities to endogenous tears.

Use of serum eye drops for moderate to severe ocular surface diseases such as dry eye, corneal epithelial defects, and inflammatory conditions has become more prevalent. Recent studies have demonstrated that the use of serum eye drops is well-tolerated by patients and associated with improvement in patient-reported outcomes and objective dry eye parameters. Production of serum eye drops may vary, treatment costs can be significant, and the quality of evidence for serum eye drop use published from randomized controlled trials is modest, particularly for long-term treatment. Accessibility remains an area for improvement and may be complemented by allogeneic serum eye drops.

Serum eye drops are frequently used as a safe, well-tolerated, and effective treatment for ocular surface disease. Further research is needed to assess long-term outcomes and improve accessibility.