This patient has evidence of evaporative dry eye in addition to some signs of aqueous deficiency. This patient has an ocular staining score (OSS) of 2 in her right eye and 3 in her left eye. The OSS is a scoring system used as part of the American College of Rheumatology (ACR) –Sjögren’s International Clinical Collaborative Alliance (SICCA) criteria for SS. Whitcher and colleagues described the OSS scoring system in detail and proposed a cutoff for abnormal OSS of 3 or more [11]. Briefly, the OSS score is a sum of corneal staining with fluorescein (score of 0–3) and conjunctival staining with lissamine green (score of 0–3 for each area—nasal and temporal). An additional point is given for corneal staining for any of the following: (1) patches of confluent staining, (2) staining in the central cornea or pupillary area, and (3) the presence of one or more filaments. It is important to use the OSS (score 0–12) when evaluating a dry eye patient for possible SS.

In addition, the patient has evidence of aqueous tear deficiency with a low Schirmer score in the right eye and a borderline score in the left eye. Although this patient did not demonstrate any filaments, the presence of filaments should always raise the suspicion for SS.

We would recommend immediately stopping all bottled tears and switching to frequent preservative-free artificial tears. It is important to treat both the aqueous deficient and evaporative components of her ocular surface disease. Patients with low or borderline low Schirmer scores (i.e., Schirmer ≤5 mm/5 min) typically will not have any excess tearing after punctal occlusion, and we have a low threshold for punctal occlusion in these patients (typically after controlling ocular surface inflammation). To address her MGD, we would also recommend starting warm compresses twice daily, lid hygiene, oral omega-3 fatty acid supplements, and/or oral doxycycline or azithromycin.

At this point, we would refer the patient to a rheumatologist for a workup. She has evidence of both aqueous tear deficiency and evaporative dry eye. In addition, she has extraocular symptoms that are suspicious for possible SS, and she has not had any significant improvement after 4 months of treatment. In general, a referral to a rheumatologist should be considered when a patient has any of the following: (1) signs of severe ocular surface disease, (2) positive OSS (OSS > 3 in either eye) or unanesthetized Schirmer ≤5 mm/5 min in either eye and positive ROS, or (3) positive OSS or unanesthetized Schirmer ≤5 mm/5 min in either eye and is refractory to treatment. The length of time when a patient is considered refractory to treatment varies by each individual, but in general, we would consider someone refractory after 4–6 months of appropriate therapy.

We would start topical cyclosporine or lifitegrast twice daily. To treat her MGD, we would consider oral doxycycline or azithromycin (if not started previously) and/or topical erythromycin ointment at bedtime. At this point, one could also consider a short course of topical steroids such as loteprednol drops or tobramycin/dexamethasone ointment with careful monitoring for side effects such as increased intraocular pressure. The patient should then return in about 3–4 months to assess for any improvement (sooner if topical steroids are started).

The patient was evaluated by her rheumatologist and has negative bloodwork for SSA, SSB, rheumatoid factor (RF), and antinuclear antibody (ANA). She then undergoes a labial salivary gland biopsy that comes back positive. The biopsy showed focal lymphocytic sialadenitis with a focus score of 1.7/4 mm ² , which was above the required diagnostic threshold of ≥1/4 mm ² .

Negative bloodwork for the traditional SS antibodies (SSA, SSB, RF, and ANA) does not rule out this diagnosis since about 40% of patients with SS lack immunologic markers in the serum. This “seronegative” subset of SS patients may have a lower rate of extraglandular manifestations [12].

The Sjo kit (Bausch & Lomb) allows for in-office testing of an expanded set of blood tests, which includes three novel antibodies that were described in a mouse model for SS [13]. In that study, the authors found that these novel antibodies appeared earlier than traditional SS antibodies in their mouse model. However, understanding the significance of these antibodies in humans requires further clinical study.

In a seronegative patient whose signs and symptoms are suggestive of SS, a minor salivary gland biopsy is a reasonable next step in the workup. Other conditions which can lead to both dry eye and dry mouth should also be entertained. These include chronic sialadenitis, sialadenosis, complications of radiation therapy, sarcoidosis, HIV, IgG4-related disease, chronic hepatitis C, and medication side effects.

It is important to work with the patient’s rheumatologist to apply published classification criteria that meet the case definition for SS. In the past decade, two sets of classification criteria have been most commonly used (Tables 5.1 and 5.2): (1) the American European Consensus Group (AECG) criteria [14] and (2) the American College of Rheumatology (ACR)/Sjögren’s International Clinical Collaborative Alliance (SICCA) criteria [15]. Both criteria sets have strengths and weaknesses but greater than 90% sensitivity and specificity for classification of a patient as having SS [14, 15]. More recently, a new set of classification criteria (ACR/European League Against Rheumatism (EULAR)) has been developed in an attempt to reconcile differences between the AECG and ACR/SICCA criteria [16]. The 2016 ACR-EULAR criteria (Table 5.3) have now been endorsed by both the American College of Rheumatology and the European League Against Rheumatism and will likely be more widely utilized in the future than older criteria sets.

While all of the above classification criteria were originally developed to define homogeneous populations of patients for research studies including clinical trials, these criteria also provide a framework for diagnostic testing as well. Therefore, in clinical practice, any patient who fulfills any of the three aforementioned criteria sets can be considered to have SS.

Because patients with SS often have low aqueous tear production, punctal occlusion plays an important role in the management of ocular surface disease in these patients. The decision of whether to perform total punctal occlusion (i.e., both the lower puncta and upper puncta) or to initially only occlude the lower puncta should be based on the severity of the aqueous tear deficiency at the time of evaluation. For SS patients with mild or moderate aqueous tear deficiency, punctal occlusion can be performed in a staged fashion with initial occlusion of the lower puncta followed at a later date by occlusion of the upper puncta if needed. In patients with severely diminished aqueous tear production, immediate total punctal occlusion is indicated as occlusion of the lower puncta alone is unlikely to have any meaningful effect on the patient’s signs and symptoms. In these cases, the small amount of aqueous tears being produced is mostly lost to evaporation. If one is considering total punctal occlusion, it is best to first perform a trial with plugs (dissolvable or non-dissolvable) followed by punctal cauterization if there is a positive clinical response and no epiphora. In addition, the degree of aqueous tear deficiency should be reassessed after the initiation of any oral secretagogues for the treatment of dry mouth in order to avoid possible epiphora. Topical steroids are initiated prior to the insertion of punctal plugs in order to decrease the buildup of inflammatory factors that may be present in the tear film.

Other treatment options that could be considered in the future for this patient include: