Introduction

Serum eye drops (SED) are a useful adjunctive treatment for patients with severe ocular surface disease (OSD), especially those with a compromised tear film. Serum contains a large number of epitheliotrophic factors that are present in tears. These factors are likely to be responsible for the therapeutic benefits observed with SED therapy compared to conventional commercially available ocular lubricants. Prescribed and over-the-counter tear substitutes primarily alleviate symptoms through reduction of friction and shear-forces caused by blink-induced biomechanical trauma. This mechanism of action appears largely to be independent of structural chemistry and viscosity of the lubricant product. By contrast, SED provide a variety of nutritional molecules such as vitamins, glucose, growth factors, and immunoglobulins. These help to restore an environment that promotes reepithelialisation and supports ocular surface health.

SED are currently classified by the Medicines and Healthcare products Regulatory Agency (MHRA) as an unlicensed medicinal product (ie, hospital ‘special’). The MHRA advises that anyone prescribing an unlicensed product must be satisfied that there is a special need for the unlicensed medicinal product, and that the unlicensed medicine should not be supplied where an equivalent licensed medicinal product can meet the special needs of the patient. This college guideline sets out recommendations and good practice points for the safe use of SED for the treatment of severe OSD. It aims to improve not only compliance with MHRA advice, but also standardise practice and improve patient morbidity. The following areas have been addressed:

  • Patient groups that may benefit from the use of SED

  • Clinical situations for the use of autologous SED (Auto-SED) and allogeneic SED (Allo-SED)

  • SED formulation, frequency of therapy, and withdrawal

  • Monitoring of treatment efficacy

The full guidance can be found online at: https://www.rcophth.ac.uk/standards-publications-research/clinical-guidelines/ and https://www.nature.com/articles/eye2017209 and a Quick Reference Guide for clinicians is provided (Figure 1). The criteria used for the grades of recommendations are found in Table 1 and a summary of recommendations are presented in Table 1a, 1b, 1c, 1d, 1e, 1f.

Figure 1
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Quick reference guide for the use of autologous and allogeneic serum eye drops in severe ocular surface disease.

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Table 1 Summary of recommendation grade
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Table 1a MHRA Guidance Note 14 (2014), supply of unlicensed medicinal products (‘specials’):
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Table 1b Serum eye drops should be considered in the following groups of patients:
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Table 1c Clinical situations where Autologous versus Allogeneic Serum Eye Drops should be considered:
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Table 1d Impact of the variability of individual nutritional constituents within supplied serum eye drops batches on clinical and patient outcomes
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Table 1e Concentration of formulation, duration and frequency of SED treatment for patients with ocular surface disease
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Table 1f Monitoring of treatment response and progression of disease
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Lay summary

Ocular Surface Disease (OSD) is a global public-health problem. Severe dryness of the eye has significant impact on a person’s physical, emotional, and social well-being.

The front of the eye is complex and has an outer surface known as tear film. A range of components contribute to how tears are made, what they contain and how they are distributed to keep the surface of the cornea smooth to enable sight and comfort. Failure of one or more of these complex components due to disease or injury results in dryness of the eye. In its severest form, OSD may lead to blinding complications.

Current practice for patients with ocular surface disease

A patient with dry eye disease is treated in a stepped approach. When commercially available artificial tears do not provide relief and the patient does not respond to conventional treatments, the ophthalmologist might suggest that a patient with severe OSD might benefit from SED which are made from blood. Artificial tears made from blood have been shown to be effective because they contain many of the substances found in normal tears. They have been found to be superior to conventional treatment for improving ocular surface health and providing comfort.

Autologous SED (Auto-SED) are made from blood donated by the patient. Patients who are not suitable to provide an autologous donation can receive allogeneic serum drops (Allo-SED) which are made from blood donated by a male volunteer donor. SED are currently reserved for people who have severe disease who have not responded to standard intervention. They are also used for those who require supportive therapy for specialist ocular surgery or for management of ocular surface injury.

The production of serum eye drops

The NHS Blood and Transplant (NHSBT) has been providing SED since 2003. It is the only accredited production facility in the UK. NHSBT prepares SED from the patient’s own blood (Auto-SED) and from individual (not pooled) male-volunteer blood donors (Allo-SED). To make the drops, the donated blood is processed to separate out the serum. Although there are variations in practice in other countries, in the UK, the serum is diluted with 50% saline and is transferred into sterile dropper bottles ready to be frozen. SED have a shelf life in the freezer of 12 months from the date of donation.

The current situation and need for guidance

Currently, SED is a highly specialised and high cost intervention for patients with OSD. The MHRA, the government body that regulates medicines and medical devices, classifies SED treatment as an unlicensed medicine. This means all licensed medical options should be considered by the doctor responsible for the patient before they are able to prescribe SED. There is geographical inequity in access to treatment that is currently being considered for exclusion from the National Tariff as a High Cost Drug. This Guidance aims to set out defined criteria for the use of SED, the monitoring of clinical and patient -reported outcomes and therefore improving patient care and safety while on treatment.

Good practice points and recommendations relevant to patients

Using the Royal College of Ophthalmologists’ Guidelines Development Manual, a systematic review of literature has been carried out in order to focus on the best evidence available so that key questions may be addressed. Recommendations affecting patients as key stakeholders may be summarised as follows.

  • SED will benefit patients who have not responded or only partially responded to licensed interventions.

  • When comparing the cost and clinical effectiveness of Auto-SED vs Allo-SED in the treatment of people with OSD, it is recommended that if a patient is unable to donate one unit of blood or a patient requires urgent treatment, Allo-SED are recommended.

  • Published studies focus on concentrations of 20, 50, and 100%. 50% is considered by NHSBT to be the best concentration for general use, although there are no internationally agreed standard procedures for the manufacture.

  • There is no clear evidence regarding the duration of treatment or the effect of treatment with SED. It is recommended that treatment should either be for a defined period or there should be an appropriate point when it is stopped in order to assess the outcome. Patient- reported outcomes are an essential tool.

Monitoring

It is recommended that patients treated with Auto-SED and Allo-SED should be enrolled on a national programme of outcome reporting that include patient reported outcomes. Reports should include: frequency and duration of treatment and serious adverse events and reactions. Attempts to withdraw treatment and duration of remission should be recorded.