Key messages

• The use of autologous serum may have no adverse effects (low certainty of the evidence).
• It is not possible to establish whether the use of autologous serum improves the quality of life, severity of dry eye, pain, or degree of corneal epitheliopathy because the certainty of the existing evidence assessed is very low.

What is the evidence.
See the evidence matrix in Epistemonikos below.

We found six systematic reviews [2],[3],[4],[5],[6],[7], which included seven primary studies reported in eight references [8],[9],[10],[11],[12],[13],[14],[15] of which, all are randomized trials.

What type of patients did the studies include? * 

All trials included patients with dry eye [8],[9],[10],[11],[12],[13],[14]. The patients average age included in the trials was 46 years.

Three trials [8],[9],[14] included patients with severe dry eye defined as Schirmer's test score less than five millimeters and tear film breakup time less than five seconds.

Two trials [8],[9] included patients with fluorescein staining scores greater than or equal to one on the Oxford scale. Only one trial included patients with dry eye due to Sjögren's syndrome [11]. One trial included only male patients with dry eye following surgery with the laser-assisted in situ keratomileusis technique [12]. Two trials did not define diagnostic criteria for dry eye [10],[13].

Regarding exclusion criteria, one trial excluded patients with uncontrolled cerebrovascular or cardiovascular disease, history of refractive surgery, lactating or pregnant women [8]. Two trials excluded patients with any other ocular pathology, severe anemia, previous use of autologous serum or use of drops for other indications [8],[9]. In addition, two trials excluded patients with a history of lacrimal occlusion or the use of contact lens [8],[14].

The remaining trials reported no exclusion criteria [10],[11],[12],[13].

What type of interventions did the studies include? * 

All trials compared the use of autologous serum versus artificial tears [8],[9],[10],[11],[12],[13],[14]. 

Regarding differences in autologous serum concentration, five trials used 20% autologous serum [8],[9],[10],[12],[14], one trial used 50% autologous serum [11] and one trial used 40% autologous serum [13].

Regarding the frequency of autologous serum administration, two trials used autologous serum four times daily [8],[9]. Two trials used autologous serum five times daily [11],[12]. One trial used autologous serum six times daily [10]. The remaining trials did not report the frequency of autologous serum use [13],[14].

What type of outcomes did they measure 

The trials reported multiple outcomes, which were grouped by the systematic reviews as follows:

• Pain, measured through a visual analog scale.

• Corneal epitheliopathy, measured through fluorescein staining.

• Quality of life, measured using the ocular surface disease index questionnaire.

• The severity of the pathology, measured through Schirmer's test and tear film breakup time test. 

• Adverse reactions.

The average follow-up of the trials was three months, with a range between two weeks and 12 months.

• The evidence presented in this summary applies to adult patients with dry eye and patients with a fluorescein staining result greater than or equal to one. 
• The patients included in these trials are adults, so the results should be extrapolated with caution to the pediatric population in the absence of direct evidence.
• The presented evidence does not apply to patients with a history of severe anemia, previous use of autologous serum or patients with previous ocular or eyelid pathology other than dry eye that required topical use of medications.

• The authors of this summary consider that the outcomes selected are critical for decision-making. They are also in line with the outcomes reported by the identified systematic reviews. 
• Corneal epitheliopathy, quality of life and severity of dry eye outcomes are necessary for visual prognosis and associated long-term repercussions. 
• Pain and adverse effects are necessary to know the symptomatology, intervention efficacy and complications during treatment.

• The use of autologous serum for dry eye may be safe compared to artificial tears, as the evidence shows little or no adverse effects. 
• Additionally, there is uncertainty on the benefits autologous serum could have on the quality of life, disease severity, pain or development of epitheliopathy, given the existing evidence. 
• Because of this, it is not possible to make an adequate balance between harms and benefits and other aspects such as costs. For this reason, patient and treating physician preference should be considered in decision-making.

• Three systematic reviews have indicated that the cost associated with the monthly use of autologous serum for dry eye can reach hundreds of dollars [3],[5],[6]. 
• However, it is not appropriate to perform a cost-effectiveness analysis until there is a proven benefit of the intervention.

• In the face of the existing evidence, both patients and physicians should lean against the use of autologous serum as a first-line treatment for dry eye.
• However, autologous serum could be a therapeutic alternative when initial treatment with environmental measures, artificial tears and pharmacological treatment has not worked.
• The use of autologous serum could be reserved for a third stage in the stepwise treatment of dry eye.

• This summary's conclusions are consistent with the identified systematic reviews [2],[3],[4],[5],[6],[7]. While the intervention may have a role in dry eye treatment, the uncertainty of the existing evidence does not allow a clear conclusion of its benefits.
• Although no clinical practice guidelines were found that make a direct comparison between the use of autologous saline and artificial tears, Tear film and Ocular surface Society and the American Academy of Ophthalmology guidelines [1],[17] mention the use of autologous serum in situations of conventional treatment failure or severe symptoms. Thus, it is not a first-line alternative for dry eye treatment. Guidelines indicate first-line treatment should be education, non-pharmacological treatment and use of ocular lubricants if deemed necessary. In addition, guidelines mention that both the high cost required for autologous serum production and the lack of international standards for its production are barriers to widespread use. These factors generate variations in doses and schedules administered to patients.

• Given the uncertainty of existing evidence, it is likely that this summary's findings will change.
• No systematic reviews were identified in the international systematic review registry platform, PROSPERO (International prospective register of systematic reviews), which evaluated the use of autologous serum versus artificial tears for dry eye treatment.
• One randomized trial was found in the International Clinical Trials Platform of the World Health Organization. However, this trial was terminated prematurely without reporting results or conclusions [18].