Connecting allergy and osmolarity

Systemic allergies affect about 20 percent of the population, and about 20 percent of these systemic allergy patients also have ocular involvement.¹

Ocular allergy is a common clinical disorder that includes dry eye syndrome in its differential diagnosis. Because many of the symptoms of dry eye and ocular allergy overlap, the clinical diagnosis becomes more challenging, highlighting the importance of diagnostic testing such as tear film osmolarity. We may even see dry eye syndrome present after years of chronic allergy, a long-lasting result of tear film imbalance and ocular inflammation.

The major type 1 immunologic hypersensitivity reaction involving the conjunctiva is commonly referred to as allergic conjunctivitis. This is a spectrum of disorders including both seasonal allergic conjunctivitis (SAC) and perennial allergic conjunctivitis (PAC).

Seasonal allergic conjunctivitis is the most common form of ocular allergy. It is an acute disorder and is contrasted from perennial (year-round) allergic conjunctivitis by its seasonal onset. Seasonal allergens can include tree pollen, grass pollen, ragweed, or outdoor molds. Perennial allergens can include dust mites, animal dander, cockroaches, and indoor molds.²

A spectrum of more chronic presentations of ocular allergic disorders includes vernal keratoconjunctivitis (VKC), atopic keratoconjunctivitis (AKC), and giant papillary conjunctivitis (GPC).^1,3

Related: Differentiating ocular allergy

Pathophysiology

The acute phase of a Type 1 hypersensitivity response in ocular allergy involves immunoglobulin E (IgE) mediated mast-cell degranulation. There is minimal presence of migratory inflammatory cells.²

A sensitized individual contacts a specific antigen, and then antigen-specific antibodies, such as IgE and IgG, cross-link and trigger mast cell degranulation. This leads to release of pre-formed allergic mediators, such as histamine, from the mast cell.

Other mediators, such as prostaglandins, thromboxanes, and leukotrienes, are formed through activation of the inflammatory cascade. Along with chemotactic factors, these mediators stimulate the early phase of IgE-mediated hypersensitivity.³

Histamine receptor stimulation (H1 is related to itching, and H2 is related to increased vascular permeability) leads to the onset of symptoms. Further activation of the inflammatory cascade and migration of eosinophils and neutrophils result in the later phase ocular allergic response. 

Related: How to improve diagnosis and treatment of allergy

Signs and symptoms

Diagnosis of ocular allergic disease is typically made based on history and clinical examination. A hallmark of ocular allergy is the symptom of itching, but signs of redness, chemosis, tearing, lid edema, and papillary reaction can also be present.¹ (See Figure 1.)

The more chronic forms of allergic eye disease are often accompanied by remodeling of the ocular surface tissues. In severe cases, the patient experiences extreme discomfort and can sustain long-lasting damage to the ocular surface tissues. (See Figure 2.)

Treatment and management

For all allergic eye disease, the only true “cure” is elimination of the offending antigen because the presence of the antigen itself is what triggers the allergic cascade in a sensitized individual.

This requirement can make it difficult to pinpoint and/or impossible to remove the offending allergen triggers from the patient’s daily life. Consider suggesting a patient give up his family pet for adoption, for instance, in a case of perennial allergic conjunctivitis due to animal dander-not a fun conversation to have chairside.

Non-pharmacological treatment approaches can include supportive therapies such as saline rinses, avoidance of eye rubbing, and cold compresses.¹ Frequent application of chilled topical lubricants can dilute the allergens and improve symptoms. Preservative-free versions of artificial tears are preferred due to the more frequent dosing in such cases.

Other recommended activities may involve reducing the burden of allergens:

• Staying indoors to avoid outdoor allergens

• Wearing sunglasses to reduce ocular exposure

• Showering at night to remove offending allergens from the body

• Frequent washing of bed linens

• Using a vacuum with a HEPA filter

Pharmacologic therapies can include anti-allergy agents and anti-inflammatory agents. Acute forms of ocular allergy tend to respond well to topical antihistamines, antihistamine/vasoconstrictor combinations, antihistamine/mast-cell stabilizer combination agents, NSAIDs, or short courses of topical corticosteroids.

For longer term symptoms or perennial cases, prophylactic use of the topical antihistamine/mast-cell stabilizer combination agents is recommended.

For late-stage cases, treatment options can be more limited. Topical corticosteroids can be used in moderate to severe cases of ocular allergy, but with that treatment comes the risk of cataract formation and elevated intraocular pressure.²

Treatment of concomitant systemic allergy symptoms with oral antihistamines or nasal allergy involvement with topical nasal spray may also help reduce overall symptoms. Immunotherapy (allergy shots) can also be effective in providing long-term relief for patients in whom a specific triggering allergen or set of allergens has been identified. 

Related: How to identify and treat allergic eye disease

The role of osmolarity

Ocular surface disease (also known as dry eye syndrome) is thought to be related to inflammation of the ocular surface. We know that the presence of ocular surface damage as well as the presence of pro-inflammatory cytokines in allergic conjunctivitis signal that inflammation is also involved.

However, studies specifically examining alterations of the tear film in patients with allergic conjunctivitis are relatively rare. It is thought that the increasing incidence of dry eye syndrome may actually be contributing to a rising incidence of conjunctival allergies because a robust tear film is necessary to wash away allergens and irritants from the ocular surface.^4-6 So, is there a connection between the two conditions that we are missing? What tests can we do perform to clarify the true cause of our patient’s symptoms, knowing that many of the presenting symptoms overlap in these two conditions?

One test to assess the tear film of ocular allergy patients is tear osmolarity. The Tear Lab measurement device is used to measure tear osmolarity, a classic hallmark of ocular surface disease as supported by the 2007 Dry Eye Workshop (DEWS) report.⁷ The manufacturer suggests a cutoff value of 308 mOsm/L (higher osmolarity means dry eye disease). It also suggests that when presented with a patient who has symptoms such as irritation but a normal osmolarity, another etiology such as allergic conjunctivitis may be a factor.⁸

Examining the research

A 2006 study supports the notion of alterations of the tear film in allergic conjunctivitis. The authors conducted Schirmer test, tear film breakup time, fluorescein staining, and tear film lipid layer interferometry in patients with SAC and radioallergosorbent test (RAST)-confirmed allergic status and compared the results with those of healthy control subjects. Notably this study did not test for tear osmolarity, although it was mentioned as a next step in the process of finding alterations in the tear film of allergic conjunctivitis patients.⁹                              

This author presented a small-scale pilot study at the American Academy of Optometry meeting in 2013 with data suggesting that there exists an inverse correlation between tear osmolarity and pollen counts.¹⁰ Additionally, no statistically significant relationship was found between dry eye symptomology by OSDI survey and tear osmolarity. Some of the limitations of this study were its small sample size, desert climate, performance in the winter months, and choice of pollen as the only specific allergen measured.

Related: Diagnosing and managing ocular allergy

A 2014 study by Bielory and colleagues presented at the American College of Allergy, Asthma & Immunology Meeting compared the prevalence and severity of dry eye disease in a national cohort of 9,216 ophthalmology patients (mean age 55 years) and 68 allergy patients (mean age, 49 years).¹¹

Patients completed a dry eye symptom questionnaire and were tested for tear hyperosmolarity (defined in this study as osmolarity >285mOsm/L with levels above 308 mOsm/L considered to be consistent with dry eye disease).

The study found that the allergy patients with concomitant dry eyes were more likely to have more severe disease. In addition, mean hyperosmolarity was more severe in allergy patients with dry eye disease than in ophthalmology patients with dry eye disease (337 vs 323 mOsm/L; P < 0.0001).

Despite the fact that this study shows that dry eye and allergy symptoms often overlap, dry eye syndrome may not be fully investigated by allergists or primary-care physicians in every patient diagnosed with systemic allergies. Recall that 20 percent of those with systemic allergies have ocular involvement.¹ When patients present with systemic allergies, it is our job as primary eyecare providers to employ additional objective testing (such as Schirmer testing, tear break-up time, conjunctival staining assessment). We must also ask about other symptoms (such as itching, foreign body sensation, or eye watering) to help these patients find the correct targeted ocular therapy for allergic conjunctivitis and/or dry eye disease when indicated.

A small scale study investigated the correlation between tear osmolarity in both keratoconus and allergic conjunctivitis patients in Brazil. Researchers found no difference in average osmolarity among healthy eyes, keratoconic eyes, and eyes with allergic conjunctivitis. Further, there was no correlation between ocular surface disease index (OSDI) and tear osmolarity. However, the OSDI was able to distinguish healthy eyes from the keratoconic and allergic eyes. The authors also suggested their location may have played a role in their results.¹²

Related: An allergist talks allergy

Other options

While the recent research appears to be mixed regarding the role of osmolarity specifically in ocular allergy, there are other types of diagnostic testing to consider.

The use of in-office diagnostic testing for matrix metalloproteinase-9 (MMP-9) may help practitioners identify and treat ocular inflammation chairside.¹³

Point-of-care testing specifically for ocular allergy using IgE markers is also in the pipeline (ATD TearScan).¹³

Research is examining new treatments specifically targeting the immunopathophysiology of ocular surface disorders in hopes of providing new potential targets and therapeutic strategies for treatment. Many of these new immunobiological modulator therapies have focused on regulating the immune-mediated inflammatory pathways that inhibit various cytokines, antibodies (like IgE), and other surface markers of various cell lines.¹⁴

You may be on the lookout for new topical glucocorticoids, leukotriene receptor antagonists, or interleukin antagonists in your office in the future. We may be using these therapies to treat all aspects of ocular inflammation-whether from ocular surface disease, ocular allergic disease, or a combination of both.

Related: How palynology and aldehydes affect allergy treatment

References

1. Chigbu DI. The management of allergic eye diseases in primary eye care. Cont Lens Anterior Eye. 2009 Dec;32(6):260-72.

2. Ono SJ, and Mark B. Abelson. Allergic conjunctivitis: update on pathophysiology and prospects for future treatment. J Allergy Clin Immunol. 2005 Jan;115(1):118-22.

3. Ventocilla MA, Majmudar PA. Allergic conjunctivitis. Medscape. 2016 Aug. Available at: http://emedicine.medscape.com/article/1191467-overview. Accessed 11/23/16.

4. Fujishima H, Toda I, Shimazaki J, Tsubota K. Allergic conjunctivitis and dry eye. Br J Ophthalmol. 1996 Nov;80(11):994-7.

5. Bielory L. Ocular allergy and dry eye syndrome. Curr Opin Allergy Clin Immunol. 2004 Oct;4(5):421-4.

6. Bielory L, Metlzer EO, Nichols KK, Melton R, Thomas RK, Bartlett, JD. An algorithm for the management of allergic conjunctivitis. Allergy Asthma Proceedings. 2013;34(5):408-420.

7. Lemp MA, Foulks GN. The definition and classification of dry eye disease. Ocul Surf. 2007 Apr;5(2):75-92.

8. TearLab Osmolarity System Clinical Utility Guide. Available at: https://www.tearlab.com/pdfs/TearLab%20Clinical%20Utility%20Guide.pdf. Accessed 11/23/16.

9. Suzuki S, Goto E, Dorgu M, Asano-Kato N, Matsumoto Y, Hara Y, Fujishima H, Tsubota K. Tear film lipid layer alterations in allergic conjunctivitis. Cornea. 2006 Apr;25(3):277-80.

10. Sicks LA, Langr K, Kuntz K, Budge B, Johnson C. Relationship between tear osmolarity and ocular allergic symptomology. Poster presented at American Academy of Optometry Annual Meeting. Seattle, WA. 2013.

11. Johnson K. Dry, Itchy Eyes Could Mean More Than Just Allergy. Medscape. 2014 Nov. Available at: http://www.medscape.com/viewarticle/834748. Accessed 11/23/16.

12. Sandrin LNA, et al. Tear osmolarity in keratoconus and allergic patients in Southern Brazil. Investigative Ophthalmology & Visual Science 56.7 (2015): 3059-3059.

13. Bowling E. How point-of-care diagnostic lab tests help clinical decisions. Optometry Times. 2016 May. Available at: http://optometrytimes.modernmedicine.com/optometrytimes/news/how-point-care-diagnostic-lab-tests-help-clinical-decisions. Accessed 11/23/16.

14. Bielory BP, Shah SP, O’Brien TP, Perez VL, Bielory L. Emerging therapeutics for ocular surface disease. Curr Opin Allergy Clin Immunol. 2016 Oct;16(5):477-86.