Characterizing the Robustness of Distinct Clinical Assessments in Identifying Dry Eye Condition of Animal Models
Hsiu-Hui Hsieh1,2, Yu-An Chang3, Szemin Chan3
1Department of Ophthalmology, Taipei Tzu Chi Hospital, The Buddhist Tzu Chi Medical Foundation, Taipei, Taiwan.
Purpose:
The study aims to characterize the robustness of distinct clinical assessments in identifying the underlying conditions of dry eye disease (DED), with a specific emphasis on the involvement of conjunctival goblet cells.
Methods:
Seven rabbits receiving surgical removal of the lacrimal and Harderian glands were divided into two groups, one with ablation of conjunctival goblet cells by topical soaking of trichloroacetic acid (TCA) to the bulbar conjunctiva (n = 3) and one without (n = 4), and the conditions of DED were assessed weekly using Schirmer test, tear breakup time (TBUT), tear osmolarity, and National Eye Institute (NEI) fluorescein staining grading. After 8 weeks, the rabbits were sacrificed, and the eyes were enucleated for histopathological examination.
Results:
Histopathological analysis revealed corneal epithelial thinning in both groups. While TCA soaking significantly decreased the density of conjunctival goblet cells, DED rabbits without TCA also showed a partial reduction in goblet cell density, potentially attributable to dacryoadenectomy. Both groups showed significant decreases in Schirmer test and TBUT, as well as an increase in tear osmolarity. In DED rabbits with TCA soaking, tear osmolarity increased markedly, suggesting that tear osmolarity is highly sensitive to loss and/or dysfunction of conjunctival goblet cells. Fluorescein staining was gradually and similarly increased in both groups, suggesting that fluorescein staining may not reveal an early disruption of the tear film until the prolonged progression of DED.
Conclusion:
The Schirmer test, TBUT, tear osmolarity, and NEI fluorescein grading are distinct, yet complementary, clinical assessments for the evaluation of DED. By performing these assessments in definitive DED rabbit models, both with and without ablation of conjunctival goblet cells, the role of these cells in the homeostasis of tear osmolarity is highlighted. Characterizing the robustness of these assessments in identifying the underlying conditions of DED will guide a more appropriate management for patients with DED.
Insights
This study highlights how tear osmolarity is sensitive to conjunctival goblet cell loss in dry eye disease (DED) models. Clinical assessments like the Schirmer test and tear breakup time are crucial for evaluating DED progression.
Area of Science:
- Ophthalmology
- Tear Film Research
- Cell Biology
Background:
- Dry eye disease (DED) is a prevalent condition affecting ocular surface health.
- Conjunctival goblet cells play a vital role in maintaining the tear film's stability and hydration.
- Understanding the diagnostic capabilities of clinical assessments in DED is essential for effective patient management.
Purpose of the Study:
- To evaluate the robustness of clinical assessments in diagnosing dry eye disease (DED).
- To specifically investigate the role of conjunctival goblet cells in DED pathogenesis and tear film homeostasis.
- To compare the sensitivity of different diagnostic tools in a rabbit model of DED.
Main Methods:
- A rabbit model of DED was established by surgical removal of lacrimal and Harderian glands.
- Conjunctival goblet cells were ablated using topical trichloroacetic acid (TCA) in a subset of rabbits.
- Clinical assessments including Schirmer test, tear breakup time (TBUT), tear osmolarity, and fluorescein staining were performed weekly.
Main Results:
- Corneal epithelial thinning was observed in all DED rabbits.
- TCA treatment significantly reduced goblet cell density; dacryoadenectomy also caused partial goblet cell loss.
- Schirmer test and TBUT decreased, while tear osmolarity increased in both groups, with a marked increase in the TCA-treated group.
- Fluorescein staining showed similar gradual increases in both groups, indicating it may detect later-stage DED.
Conclusions:
- Clinical assessments like Schirmer test, TBUT, and tear osmolarity are valuable and complementary for DED evaluation.
- Conjunctival goblet cells are critical for maintaining tear osmolarity homeostasis.
- Robust characterization of these assessments aids in guiding appropriate DED management strategies.


