ALLOGENEIC VERSUS AUTOLOGOUS SERUM EYE DROPS: A DOUBLE-BLIND RANDOMIZED CROSS OVER TRIAL

Serum eye drops (SEDs) are used to treat patients with extreme dry eyes and
other corneal defects. Serum is used in severe ophthalmic cases where
conventional eye drops (artificial tears) have insufficient effect. The use of
SEDs in dry eye patients usually has a rapid effect. Most patients claim the
effect to be instantaneous, and all symptoms improve within 48 hours.
There is evidence suggesting that substances in serum may help in the healing
of epithelial defects, such as epidermal growth factor, fibroblast growth
factor, fibronectin, and/or vitamin A. However, the precise serum factor
responsible for alleviating the patient*s complaints is currently not known.
Commonly, autologous SEDs are used, but they are replaced more and more by
allogeneic SEDs prepared from donor serum.
Preparing autologous SEDs is often problematic. Patient-related problems are
old age, having to travel to the hospital, traveling with low vision, and
sometimes immobility due to other diseases. Sometimes venipuncture is
impossible due to poor venous access. Further, the patient can be unable to
donate large amounts of whole blood. Patients affected by microbial infections
are also unsuitable for collection of blood for autologous SEDs. Logistically,
it takes time to prepare these drops, causing significant waiting (or
traveling) time for the patient. The use of allogeneic SEDs will prevent the
above, and may provide an off-the-shelf alternative for autologous SEDs.
Allogeneic SED are derived from healthy voluntary, non-remunerated male donors
with blood group AB. The use of allogeneic SED could provide blood bank
controlled quality, a safer product in larger quantities that is quickly
available for each patient.
No double blind randomized trials are known to exist to detect a difference in
result between the effect of allogeneic SED or autologous SED. Our hypothesis
is that both autologous and allogeneic SEDs (both in a 1:1 dilution with
saline) result in comparable outcomes.

The main objective is to determine the Ocular Surface Disease Index (OSDI)
outcomes of autologous and allogeneic SEDs compared to baseline values.

Prospective double blinded randomized cross-over trial.
There are 3 sections in the treatment period:
1. In the first month, either allogeneic or autologous eye drops will be
provided. The patient nor the physician will know the type of SEDs they receive
2. In the second month, regular eye drops (the same as the ones used before
onset of the study) will be applied (wash out period)
3. In the third month, depending on the treatment they received in the first
month, either allogeneic or autologous eye drops will be provided.
In addition, in the month prior to start of the study, the patient has to
remain on their current eye medication. The medication used in the period prior
to the study will also be used during the second month of the treatment period.

treatment with autologous or allogeneic serum eye drops

Patients have to visit the ophthalmologist four times (at entry and upon
completion of each monthly treatment period) for physical examinations. Each
time, the patients have to fill out the OSDI questionnaire; the Schirmer*s eye
test and tear break up time will be performed, and a photo will be taken to
count the number of corneal punctates. Once, they have to comment on the user
friendliness of the application device. Added discomfort associated with
participation is unlikely, as the SED treatment is intended to alleviate
complaints; however, during the one month wash-out period using non-serum
(conventional) eye drops, complaints may return.
Allogeneic SEDs are obtained from Sanquin Blood Supply in the Netherlands
according to standard procedures. We postulate that these SEDs have the same
effectiveness as autologous SEDs, therefore we do not suspect that there is
increased risk or discomfort for the patient. All serum donors are tested twice
with an interval of several months to cover the window of infectivity for all
main blood-borne diseases before a serum unit is released for use, according to
highly specific, standardized testing in the Netherlands.
Participating patients will donate sufficient blood (minimum, 100 mL) to
prepare autologous SEDs for one month. Currently, in the autologous setting,
only patients from whom sufficient serum can be drawn to make SEDs can use
them. In the future, patients with severe dry eye syndrome who are unable to
give serum for autologous SEDs, can be treated with SEDs from an allogeneic
source, thereby potentially improving their prognosis.