Autologous serum tears: An addition to the arsenal in
the fight against dry eye
Jeffrey Kennedy, MD
Abstract
Refractory dry eye and ocular surface disease is a common but complex problem presenting to the
ophthalmologist. Understanding the underlying pathophysiology is essential to optimizing management
of complex patients. Here we present a case of a patient with multifactorial ocular surface disease which
demonstrated an excellent response autologous serum tears. Autologous serum tears should be
considered in the treatment of patients with refractory dry eye and ocular surface disease.
History
A 43 year old female with history of system lupus erythematosus (SLE) and Sjögren’s syndrome (SS)
presented to University of Colorado Hospital eye clinic for a second opinion regarding management of
her ocular surface disease. The patient had previously been managed by an outside cornea specialist,
but continued to experience foreign body sensation and chronic ocular irritation. At the time of
presentation, she was using preservative free artificial tears 6 times daily, loteprednol etobanate 0.2%
suspension 1 to 2 times daily, cyclosporine ophthalmic emulsion 0.05% twice daily, and azithromycin 1%
suspension every other day. She had previously been given a trial of punctal occlusion but was unable to
tolerate punctual plugs. She also followed with an outside rheumatologist, and SLE was managed with
systemic hydroxychloroquine.
Exam
The patient’s visual acuity was 20/20 in both eyes. Intraocular pressure, pupils and motility were
unremarkable. Anterior segment examination demonstrated significant blepharitis with scarring of
meibomian gland orifices, 1+ conjunctival injection, 2+ superficial punctate keratopathy (SPK),
decreased tear lake, and tear film break up time of less than 5 seconds in both eyes. Examination of the
anterior chamber, iris, lens, vitreous and dilated fundus examination were unremarkable.
Discussion and Diagnosis
Dry eye is a common problem which can have significant impact on patient’s quality of life. The 2007 Dry
Eye Workshop (DEWS) defined dry eye as “a multifactorial disease of the tears and ocular surface that
results in ocular discomfort, visual disturbance, and tear film instability. It is accompanied by increased
osmolarity of the tear film and inflammation of the ocular surface.” Dry eye was further categorized into
aqueous deficiency and evaporative dry eye [1].
Amongst patients with clinically significant dry eye syndrome, 10.9-11.6% have underlying SS, and ocular
surface symptoms are often more severe in this subset of patients [2] [3]. SS is characterized by
lymphocytic infiltrate of the lacrimal and other exocrine glands leading to decreased basal and reflex
tear production. As in this case, SS is often associated with other autoimmune disorders such as SLE,
rheumatoid arthritis or systemic sclerosis. [4]
Blepharitis is the most common cause of evaporative dry eye, and has been observed by
ophthalmologists in up to 37% of patients [1] [5]. In addition to aqueous deficiency, meibomian gland
dysfunction (MGD) is more common in patients with SS and SLE. Significant MGD as observed in this
case, results in decreased tear film lipid layer, decreased tear stability and increased tear evaporation
rate [6].
The patient described above has a complex ocular surface disease with both aqueous deficiency and
evaporative disease processes. Patients such as this require a multifactorial approach to addressing the
underlying pathology in its entirety.
Replacement therapy with artificial tears remains first line therapy for patients with dry eye and ocular
surface disease. The advent of preservative free artificial tears has allowed for frequent use without the
complications of preservative related toxicity. Viscous gel and ointment formulations also provide longer
lasting lubrication and are especially useful at night, when there will be an extended time period
between applications and when patients will be least bothered ointment related blurred vision.
Punctal occlusion either by plugs or cautery can also be used to preserve the available tear film.
Unfortunately, this patient was unable to tolerate punctual plugs and was hesitant to proceed with
punctual cautery.
Topical anti-inflammatory agents are often used as second line agents for treatment of dry eye.
Hyperosmolarity of the dysfunctional tear film leads to an inflammatory cycle which leads to progression
of ocular surface disease [1]. Topical cyclosporine and corticosteroids can help to break this
inflammatory cycle and provide symptomatic relief.
Tetracyclines can be used for both their antibacterial and anti-inflammatory properties in treatment of
posterior blepharitis. A decrease in bacterial flora may minimize production of bacterial lipase, thereby
minimizing breakdown of meibomian lipid products. Tetracyclines also reduce production of
inflammatory mediators at the ocular surface. Topical or a short course of oral tetracyclines are an
excellent adjunct therapy for posterior blepharitis [1].
After initial evaluation, the patient was switched from topical azithromycin to a 3 month course of oral
doxycycline 50mg bid, and she was started on nightly tobramycin/dexamethasone 0.3%/0.1% ointment.
She was instructed on proper lid hygiene and use of warm compresses for management of MGD. After 4
weeks, she reported mild improvement but still had significant symptoms and an unchanged exam.
Twenty five percent (25%) autologous serum tear drops four times daily were added to her regimen.
One month later the patient reported significant improvement in ocular irritation and redness; on
examination SPK and conjunctival injection were nearly resolved. The patient’s symptoms have been
well controlled on this regimen for over 1 year.
In addition to supplemental lubrication, serum tears provide essential components to the ocular surface
epithelium which help to regulate epithelial growth, differentiation, maturation and proliferation. These
essential components include epidermal growth factor, hepatic growth factor, fibroblast growth factor,
transforming growth factor beta and others [7]. Levels of these components in tears are altered in
disease states including dry eye and this may contribute to persistent surface disease [8].
Supplementation with these growth factors promotes ocular surface health and can help to alleviate
symptoms in refractory dry eye. Autologous serum tears provide a vehicle for these essential
components. In a recent double blind crossover study, Celebi et al showed that serum tears were
superior to preservative free artificial tears in stabilizing the tear film and improving patient symptoms
in patients with primary dry eye syndrome [9]. In addition, Tsubota et al previously demonstrated that
serum tears have significant efficacy in a cohort of patients with SS. [10].
Despite their proven efficacy in clinical trials, autologous serum tears are not FDA approved, and there is
no standard protocol for their production. Informed consent should be obtained prior to prescribing
serum tears. Only specialized labs and pharmacies offer autologous serum drops. In addition, use of
serum tears requires regular blood draws for the patient, as well as out of pocket cost that is not
covered by most insurance providers. These obstacles may make use of serum tears logistically
challenging for both patients and health care providers.
Conclusion
Dry eye and associated ocular surface disease is a common but complex problem requiring a
multifactorial treatment approach. Although use of serum tears may be logistically challenging, the
proven efficacy of autologous serum tears makes them an important adjunct to the treatment regimen
in patients with refractory dry eye.
References
1. The Ocular Surface (2007 Report of the International Dry Eye WorkShop). Ocul Surf 2007; 5: 65-206.
2. Akpek EK, Klimava A, Thorne JE, Martin D, Lekhanont K, Ostrovsky A. Evaluation of patients with dry
eye for presence of underlying Sjögren syndrome. Cornea 2009; 28: 493-497.
3. Liew M, Zhang M, Kim E, Akpek EK. Prevalence and Predictors of Sjögren's Syndrome in a Prospective
Cohort of Patients With Aqueous-Deficient Dry Eye. Br J Ophthalmol 2012; 96: 1498-1503.
4. Kassan SS, Moutsopoulos HM. Clinical Manifestations and Early Diagnosis of Sjögren Syndrome. Arch
Intern Med 2004; 164: 1275-1284.
5. Lemp MA, Nichols KK. Blepharitis in the United States 2009: a survey-based perspective on prevalence
and treatment. Ocul Surf 2009; 7(2 suppl): S1-S14.
6. Schaumberg DA, Nichols JJ, Papas EB, et al. The International Workshop on Meibomian Gland
Dysfunction: report of the subcommittee on the epidemiology of, and associated risk factors for, MGD.
Invest Ophthalmol Vis Sci 2011; 52: 1994-2005.
7. Geerling G, MacLennan S, and Hartwig D. Autologous serum eye drops for ocular surface disorders..
Br J Ophthalmol 2004; 18: 1467-1474.
8. Imanishi J, Kamiyama K, Iguchi I, Kita M, Sotozono C, Kinoshita S. Growth factors: importance in
wound healing and maintenance of transparency of the cornea. Prog Retin Eye Res 2000; 19: 113-129.
9. Celebi ARC, Ulusoy C, Mirza GE. The efficacy of autologous serum eye drops for severe dry eye
syndrome: a randomized double-blind crossover study. Graefes Arch Clin Exp Ophthalmol 2014; 252:
619-626.
10. 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; 83: 390-395.