Tear Dysfunction

A qualitative or quantitative abnormality of the tear film may occur as a result of

• change in the amount of tear film constituents

• change in the composition of the tear film

• uneven dispersion of the tear film because of corneal surface irregularities

• ineffective distribution of the tear film caused by eyelid–globe incongruity

The amount or composition of the tear film can change because of aqueous deficiency, mucin deficiency or excess (with or without associated aqueous deficiency), lipid abnormality (meibomian gland dysfunction), and/or ocular surface exposure. The inciting factors for a dysfunctional tear film are multifactorial (see Fig 7-6).

Increases in tear film osmolarity are diagnostic of DES and can be found in blepharitis and with contact lens use. The preocular tear film is dispersed unevenly with an irregular corneal or limbal surface (inflammation, scarring, dystrophic changes) or poor contact lens fit. Eyelid–globe incongruity results from congenital, traumatic, or neurogenic eyelid dysfunction or absent or dysfunctional blink mechanism and results in ineffective tear film distribution. Also, although overall hormone balance is unique to each person, estrogen and androgen deficiencies—combined with stress, pollution, and poor diet—produce a number of signs and symptoms, including dry eye, especially in postmenopausal women. In addition, the quality and quantity of the tear film diminish with age.

Diagnostic tests for tear dysfunction include tear breakup time, fluorescein staining, lissamine green staining, rose bengal staining, osmolarity testing, Schirmer test, tear meniscus evaluation, and MMP-9 testing.

There is increasing evidence that DES is associated with ocular surface inflammation (Fig 7-7). In various studies, adhesion molecule expression by conjunctival epithelial cells, T-cell infiltration of the conjunctiva, and increases in soluble mediators (cytokines and proteases) in the tear film have been found in patients with DES. Preliminary clinical studies have shown that using tear substitutes to treat patients with DES may reduce tear osmolarity and improve ocular symptoms. Moreover, a variety of anti-inflammatory drugs (including corticosteroids, cyclosporine, lifitegrast, and doxycycline) have been used as therapy for DES and observed to improve the clinical symptoms of these patients (Fig 7-8).

Figure 7-7 Ocular surface inflammation in DES. CL = contact lens; IL -1 = interleukin-1; MAPK = mitogen-activated protein kinase; MGD = meibomian gland dysfunction; MMPs = matrix metalloproteinases; NF-κB = nuclear factor kappa-light-chain-enhancer of activated B cells; NSDE = non–Sjögren dry eye; SSDE = Sjögren syndrome dry eye; TF = tear film; TNF-α = tumor necrosis factor alpha.

(Modified with permission from The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf. 2007;5(2):75–92.)

Figure 7-8 Targets of anti-inflammatory therapies for DES. C = cyclosporine A; L = lifitegrast; MMPs = matrix metalloproteinases; S = (cortico)steroids; T = tetracycline.

(Modified with permission from Pflugfelder SC. Antiinflammatory therapy for dry eye. Am J Ophthalmol. 2004;137(2):340.)

Topical cyclosporine A emulsion and lifitegrast are approved by the US Food and Drug Administration for treating the inflammatory component of DES. Cyclosporine, a fungusderived peptide emulsion, has been shown to be effective in stimulating aqueous tear production in patients with DES. Lifitegrast, a lymphocyte function–associated antigen-1 (LFA-1) antagonist that inhibits binding of ICAM-1 to LFA-1, has been shown to reduce inferior corneal staining and provided greater symptom relief in treated patients with DES than in control groups. No significant systemic or ocular adverse events (except for burning symptoms) were observed.

See also BCSC Section 8, External Disease and Cornea, which discusses DES in greater detail.

• Willcox MDP, Argüeso P, Georgiev GA, et al. TFOS DEWS II tear film report. Ocul Surf. 2017;15(3):366–403.

Excerpted from BCSC 2020-2021 series: Section 2 - Fundamentals and Principles of Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.