Clinical trial NCT03395431: Fingerprick Autologous Blood (FAB) in Severe Dry Eye Disease (DED)
Official title: The Feasibility of Fingerprick Autologous Blood (FAB) As a Novel Treatment for Severe Dry Eye Disease (DED)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Dry Eye Syndromes
Keywords: Autologuous serum
dry eyes disease
fingerprick blood
Lead sponsor: Bedford Hospital NHS Trust
Sponsor class: OTHER
Collaborators: name: Anglia Ruskin University
First posted: 2018-01-10
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A single blind parallel group randomized control trial
Primary purpose: TREATMENT

Brief summary: Dry eye disease (DED) is an umbrella term encompassing a range of diseases estimated to affect 14% of all adults aged 48 to 91. If left untreated, DED can lead to severe reduction in the quality of life of the sufferer. It can also cause loss of vision, pain in response to light, painful recurring stabbing sensations, and the feeling of grit in the affected eye(s). No curative agents for DED exist. Available conventional treatment options for DED such as artificial tears often only alleviate symptoms, have limited effectiveness, and in most cases patients may fail to respond; although the exact rate of treatment failure is unavailable in the published literature. Crudely, human tears with its vast constituents is essentially filtered blood and as such is an obvious source for a "tear mimic" containing the substances of tears. Blood, and several blood derived products, including autologous serum, have been studied as tear substitute candidates. This study proposes to test the use of finger prick autologous blood (FAB) technique in which whole blood is applied to the eye from a cleaned finger.

Detailed description: Autologous serum (AS) eye drops have been found in uncontrolled trials to be beneficial in DED patient by improving the ocular surface and reducing symptoms. Obtaining autologous serum requires frequent drawing of blood from the patient- a feature that excludes patients with anaemia or heart failure from using AS. Furthermore it also appears that 100% autologous serum is more beneficial than 50% serum and requires larger volumes of blood and/or more frequent venesection. Patients using AS also require access to a fridge as the product needs to be stored at low temperatures; a factor that is likely to be inconvenient for patients. In addition, AS is obtained by processing clotted blood which is often too expensive for the health service to consistently purchase, given the initial cost of £1653.56 and subsequent three-monthly cost of £1131.27 per patient.

The relatively high cost represents the biggest hurdle in the use of AS and is often the reason for delay or inaccessibility in starting treatment for DED using AS. However, we propose that finger prick autologous blood may be a simpler, cost-effective and possibly more acceptable method for treating dry eye disease. For this reason, this study proposes to test the use of finger prick autologous blood (FAB) technique in which whole blood is applied to the eye from a cleaned finger.

The proposing team have completed an exploratory study on the use of finger-prick autologous blood (FAB) for persistent epithelial defects and severe dry eye disease and preliminary results indicate improvement with no adverse events reported. The exploratory study included 16 patients with a diagnosis of severe to moderate dry eye syndrome and used the FAB method for treatment. The findings of the study demonstrated mean improvements in visual acuity, Oxford corneal staining grade, tear breakup time, Schirmer's test and dry eye disease questionnaire score. The response rate from participants was good with only a single patient who met the inclusion criteria not wishing to participate in the trial on the advice of their general practitioner. Both the amount of staining (indicating inflammation and ocular surface damage) and their DED questionnaire scores (indicating severity of their symptoms and impact on quality of life) showed mean improvement which reached statistical significance.

Eligibility criteria: Inclusion Criteria:

* Patient age ≥ 18 years
* Severe symptomatic dry eye disease diagnosed by: Ocular surface disease index (OSDI) score of greater than 33; OR Oxford Corneal Staining grade 2 or greater; OR Schirmer's without anaesthesia \<5mm at 5 minutes
* Patients on artificial tears and/or lubricating drops/gel two or more times a day
* Patient able to give consent
* Patients able and willing complete the quality of life (QoL) questionnaires required for the study

Exclusion Criteria:

* Fear of needles
* Unable or not willing to carry out repeat finger pricks
* Patients with infected finger/s or systemic infection or on systemic antibiotics for infection.
* Patients with active ocular infection, active immunological corneal melt, or recurrent corneal erosion.
* Pregnant or breast feeding women
* Previous use of FAB treatment (e.g. from exploratory study)
* Systemic illness causing immune system deficiency
* Graft versus host disease
* Previous use of autologous serum within 3 months

Primary outcomes:
measure: Number of patients recruited into the study within the specified time frame
timeFrame: 12 months
measure: Number of patients who adhere to trial protocol
timeFrame: 12months
Secondary outcomes:
measure: Reduction in corneal inflammation as indicated by staining on front of the eye
timeFrame: 3 months
measure: Patient pain and symptoms scores
timeFrame: 3 months
measure: Improvement in objective signs of dry eye disease as indicated by visual acuity
timeFrame: 3 months
measure: Willingness for patients to be randomised and acceptability of the intervention
timeFrame: 3 months
measure: Impact on patients' quality of life
timeFrame: 3 months
measure: Cost to the NHS and patient
timeFrame: 3 months
measure: Intraocular pressure (IOT)
timeFrame: 3 months
Other outcomes:
Locations:
Study officials:
References:
citation: Poon AC, Geerling G, Dart JK, Fraenkel GE, Daniels JT. Autologous serum eyedrops for dry eyes and epithelial defects: clinical and in vitro toxicity studies. Br J Ophthalmol. 2001 Oct;85(10):1188-97. doi: 10.1136/bjo.85.10.1188.
citation: Tsubota K, Goto E, Fujita H, Ono M, Inoue H, Saito I, Shimmura S. Treatment of dry eye by autologous serum application in Sjogren's syndrome. Br J Ophthalmol. 1999 Apr;83(4):390-5. doi: 10.1136/bjo.83.4.390.
citation: Fox RI, Chan R, Michelson JB, Belmont JB, Michelson PE. Beneficial effect of artificial tears made with autologous serum in patients with keratoconjunctivitis sicca. Arthritis Rheum. 1984 Apr;27(4):459-61. doi: 10.1002/art.1780270415. No abstract available.
citation: Than J, Balal S, Wawrzynski J, Nesaratnam N, Saleh GM, Moore J, Patel A, Shah S, Sharma B, Kumar B, Smith J, Sharma A. Fingerprick autologous blood: a novel treatment for dry eye syndrome. Eye (Lond). 2017 Dec;31(12):1655-1663. doi: 10.1038/eye.2017.118. Epub 2017 Jun 16.
citation: Balal S, Udoh A, Pappas Y, Cook E, Barton G, Hassan A, Hayden K, Bourne RRA, Ahmad S, Pardhan S, Harrison M, Sharma B, Wasil M, Sharma A. The feasibility of finger prick autologous blood (FAB) as a novel treatment for severe dry eye disease (DED): protocol for a randomised controlled trial. BMJ Open. 2018 Oct 31;8(10):e026770. doi: 10.1136/bmjopen-2018-026770.