New Dry Eye Treatment: IVIG drops; Intravenous Immune Globulins Drops

Interesting article by two former colleagues at Harvard Medical School, Dr. Rosenblatt and Dr. Jain.
We are investigating this option for one of our patients. 

Here are the key points of the article.
1. What was used: Intravenous Immune Globulins (IVIG; Flebogamma 50 mg/mL) was diluted with normal saline to prepare a 4 mg/mL immune globulin preparation which we have termed Ocular Surface Immune Globulin (OSIG), in keeping with nomenclature based on the route of administration of immune globulins. 

2. OSIG-eye drops (4 mg/mL) was used two times a day for eight weeks to treat DED patients who had high ACPA in their OSW ( Identifier: NCT03992482). 

3. Patients treated: had several subtypes of DED were included in this study. Ocular GVHD was diagnosed in the study PI’s clinic (SJ) based on the Chronic Ocular GVHD consensus scoring algorithm [25]. Sjögren’s syndrome diagnosis was made by referring physicians. Diagnosis of other DED subtypes (e.g., MGD and discordant DED) was made in the study PI’s clinic based on standard clinical and imaging criteria.

4.  Inclusion criteria:

a. > 18 years or older

b. ocular symptoms related to DED for at least 6 months and a score on the Ocular Surface Disease Index (OSDI) of ≥13.

c. Had  2 signs in at least one eye: 

-a conjunctival Lissamine green staining score of ≥1 (on a scale ranging from 0 to 6),

-a corneal Lissamine green staining score of ≥2 (on a scale ranging from 0 to 15)

– a tear break-up time of 7 s or less

– Schirmer’s test without anesthesia of ≤9 mm in 5 min. 

d. All patients had an ACPA value of ≥4.4 units in OSW of either eye at any time in the past. 

e. Participants were permitted to continue their chronic ocular treatments, including the use of artificial tears, ointments, prescription eye drops (Restasis, Xiidra, Steroids), eyelid massage, or warm compresses. 

f. Subjects were asked to maintain their ocular treatments unchanged in frequency of use for the duration of the study. 

g. Subjects wearing contact lenses or using serum tears were asked to discontinue them for 2-weeks prior to being enrolled (baseline visit) and were required to not use them for the duration of the study. 

h. All systemic medications continued unchanged. 

5. Exclusion criteria: any allergy to pooled human immune globulins or any similar products. Patients with epithelial defects, active ocular infection or ocular allergies and history of ocular surgery within 3 months of baseline visit were also excluded.

Original Research

Pathological consequences of anti-citrullinated protein antibodies in tear fluid and therapeutic potential of pooled human immune globulin-eye drops in dry eye disease



To investigate the role of Anti-Citrullinated Protein autoantibodies (ACPAs) in the pathology of dry eye disease (DED) and the therapeutic potential of pooled human immune globulin-eye drops in these patients.


We investigated the presence of citrullinated proteins and ACPAs in ocular surface wash (OSW) and conjunctival impressions from patients with DED and determined the pathological consequences of OSW with high ACPA using in vitro experiments and in vivo murine models. We performed a randomized, double-masked, pilot clinical trial to determine the safety, tolerability and preliminary efficacy of using pooled human immune globulin-eye drops to treat DED patients with ACPAs in OSW.


We found that neutrophils are a source of citrullinated proteins on the ocular surface of DED patients. We detected significantly higher immunoglobulin amount and presence of several species of ACPAs in OSW from DED patients. We also found that OSW with high ACPA contributes to production of NETs, and that ACPAs cause ocular surface disease in murine eyes, both of which are reduced with addition of Immune globulins. As compared to Vehicle treatment, pooled human immune globulin-eye drops (IVIG 4 mg/mL) twice a day for 8 weeks caused significant reduction in signs and symptoms of DED with no difference in tolerability or adverse events.


This is the first report demonstrating ACPAs in OSW of DED patients and their contribution to ocular surface disease. The first-in-human clinical trial suggests that pooled immune globulin-eye drops are a potential new class of biologic therapies for Dry Eye patients.


Dry eye
Pooled human immune globulin
Sjögren’s syndrome
Shopping Cart