Novel And Emerging Strategies
Autologous Serum Eye Drops
Autologous serum eye drops are made from the patient’s blood, which contains some of the same nutrients normally found in tears. Autologous serum eye drops are a good therapeutic option in severe cases of dry eye that do not respond to other treatments. The components of autologous serum eye drops include vitamin A, anti-inflammatory compounds, and various growth factors that promote healing and increase lubrication of the eye surface. In addition, these eye drops contain immunoglobulins (eg, IgA and IgG) and lysozyme, which have antibacterial properties, and are free of preservatives (Pan 2013; Lin 2014; Foulks 2015; Semeraro 2016).
In a double-blind clinical trial, two weeks of treatment with autologous serum eye drops in patients with severe dry eyes resulted in significantly better symptom improvement than conventional artificial tears (Urzua 2012). Several other clinical studies of autologous serum eye drops in dry eye disease have shown positive effects with long-term (up to one year) treatment (Rybickova 2016; Hussain 2014; Jirsova 2014; Mondy 2015). However, a review of clinical trials found inconsistent results with use of autologous serum eye drops for dry eye. Large, randomized controlled trials are needed to further evaluate their potential benefits (Pan 2017).
Treatment of dry eyes with autologous serum eye drops has a good safety record (Soni 2016; Hussain 2014). Limitations of use of autologous serum eye drops include risk of infection (a rare side effect), inconvenience of preparation, and refrigeration requirements (Foulks 2015; Soni 2016).
Lacrimal Gland Repair
A possible new treatment option for dry eyes involves the use of progenitor cells or stem cells to restore normal function to the eyes’ lacrimal (tear) glands. Like stem cells, progenitor cells can differentiate into specific cell types (Gromova 2016; Ackermann 2015; Tiwari 2014).
In an animal study, progenitor cells isolated from the lacrimal glands of normal mice were injected into the lacrimal glands of mice with a disease similar to Sjögren syndrome. The donor progenitor cells successfully differentiated into lacrimal gland secretory cells and substantially improved glandular structure and function in the diseased mice. Tear production significantly increased in the treated mice compared with saline-injected control mice (Gromova 2017).
Belimumab (Benlysta) is a monoclonal antibody that inhibits B-cell activating factor, a cell-signaling compound that is overproduced in primary Sjögren syndrome and contributes to the autoimmune response. Belimumab, administered by intravenous infusion or subcutaneously, is FDA approved for the treatment of systemic lupus erythematosus (another autoimmune disease) and has undergone early-phase clinical trials in Sjögren syndrome patients (De Vita 2015; Seror 2015; Mariette 2015; Yapa 2016).
In one study, treatment with belimumab for 52 weeks benefited about 60% of patients with primary Sjögren syndrome. Decreases in swelling of salivary glands and systemic disease activity were observed at six months and persisted for more than one year. Belimumab treatment also led to modest improvements in fatigue and pain (De Vita 2015; Mariette 2015).
Belimumab is generally well tolerated. The most common adverse effects include infections, infusion reactions, hypersensitivity, headache, nausea, and fatigue. Insomnia, anxiety, and depression have also been reported (Srivastava 2016; Dubey 2011).
Mesenchymal Stem Cells
Mesenchymal stem cells are found in certain tissues in the body and have the ability to differentiate into a range of different cell types. Mesenchymal stem cells secrete anti-inflammatory molecules and have immune-modulating properties. Stem cells infused into the blood have been shown to migrate to the salivary glands where they suppress inflammation (Ullah 2015; Xu 2012; Mavragani 2013).
In a clinical trial in patients with primary Sjögren syndrome, intravenous mesenchymal stem cell therapy markedly increased salivary flow rate, suppressed autoimmunity, and improved disease symptoms. The treatment was well tolerated with no adverse effects (Xu 2012).
Topical Nerve Growth Factor
Nerve growth factor is a signaling molecule that regulates the growth and maintenance of the nervous system and plays a role in wound healing (Qin 2017). Nerve growth factor has been detected in several tissues outside of the nervous system as well as in human tears. Dry eye appears to increase the concentration of nerve growth factor in tears (Lin 2014; Lambiase 2011; Chang 2008; Chen 2014; Takano 2017). Nerve growth factor eye drops have been shown to increase tear production and density of mucous-secreting cells in a dog model of dry eye (Coassin 2005). Other evidence from animal and human studies indicates that topical application of nerve growth factor may relieve dry eye caused by various conditions (Lambiase 2011; Lambiase 2009; Lee 2005; Chang 2008; Aloe 2015). Larger studies are needed to confirm the efficacy of topical nerve growth factor in treating dry eye.
Innovative Laboratory Testing and Diagnostic Approaches
A challenge for Sjögren syndrome patients is they frequently do not receive a formal diagnosis until many years after their symptoms initially manifest. Earlier diagnosis of Sjögren syndrome may allow for prompt initiation of treatment and improved quality of life (Chen 2015; Hamm-Alvarez 2014).
A number of biomarkers that may be used for early assessment and diagnosis of Sjögren syndrome have been identified. These include cathepsin S, B-cell-activating factor, and myxovirus resistance protein A (Nishikawa 2016; Chen 2015; Hamm-Alvarez 2014).
Cathepsin S. Tear levels of an enzyme called cathepsin S appear able to serve as a cost-effective, fast, and noninvasively measurable biomarker for Sjögren syndrome that may lead to early diagnosis (Hamm-Alvarez 2014).
Markedly elevated levels of cathepsin S have been found in tears of Sjögren patients compared with tears of healthy controls. Tear levels of cathepsin S in Sjögren patients were also higher than levels in people with dry eyes unrelated to Sjögren syndrome and those with other autoimmune diseases (Hamm-Alvarez 2014).
B-cell-activating factor. B-cell-activating factor is involved in the development of several autoimmune diseases. Levels of B-cell-activating factor are increased in blood, tears, and saliva of Sjögren patients. Overproduction of B-cell-activating factor in Sjögren syndrome leads to destruction of glandular cells and decreased production of saliva. Among Sjögren patients, those with lymphoma have higher B-cell-activating factor levels than patients without lymphoma (Nishikawa 2016; Mariette 2016; Maslinska 2015).
Myxovirus resistance protein A. Elevated levels of a cytokine called type I interferon have been found in the blood and salivary glands of Sjögren patients. Type I interferon is a major contributor to chronic inflammation and glandular damage in Sjögren syndrome, and higher levels are associated with more severe disease. Since blood and immune cell levels of myxovirus resistance protein A are significantly correlated with type I interferon activity in individuals with primary Sjögren syndrome, myxovirus resistance protein A has been proposed as a useful disease biomarker (Chen 2015; Nishikawa 2016; Rischmueller 2016; Li 2013).