In vivo Confocal Microscopy Evaluation of Meibomian Gland Dysfunction in Dry Eye Patients with Different Symptoms

Abstract

Background: Dry eye patients suffer from all kinds of symptoms. Sometimes, the clinical signs evaluation does not disclose any obvious difference in routine examination; in vivo confocal microscopy (IVCM) is a powerful tool for ocular surface disease. This study aimed to clarify meibomian gland (MG) alterations in dry eye patients with different symptoms and to compare the findings using IVCM.

Methods: A total of sixty patients were recruited, all subjected to Ocular Surface Disease Index (OSDI) and Salisbury Eye Evaluation Questionnaire (SEEQ), and questionnaires for the assessment of dry eye symptoms before clinical sign examinations were given to the patients. Finally, IVCM was applied to observe MG's structure. Statistical analysis was performed using the t-test, Mann-Whitney U-test and Spearman correlation analysis. The differences were statistically significant when P< 0.05.

Results: In the severe symptom group, OSDI and SEEQ scores were significantly higher (P< 0.05) compared with the mild symptoms group. All other clinical sign examinations had no statistical difference in the two groups (P> 0.05). However, all the IVCM-observed data showed that patients with severe symptoms had more significant fibrosis in MG (acinar unit area 691.87 ± 182.01 μm2 for the severe, 992.17 ± 170.84 μm2 for the mild; P< 0.05) and severer decrease in the size of MG acinar units than those observed in patients with mild symptoms (MG acinar unit density [MGAUD] 70.08 ± 18.78 glands/mm2, MG acinar unit longest diameter [MGALD] 51.50 ± 15.51 μm, MG acinar unit shortest diameter [MGASD] 20.30 ± 11.85 μm for the severe, MGAUD 89.53 ± 39.88 glands/mm2, MGALD 81.57 ± 21.14 μm, MGASD 42.37 ± 14.55 μm for the mild;P< 0.05). Dry eye symptoms were negatively correlated with MG confocal microscopic parameters and positively correlated with conjunctival inflammatory cells and Langerhans cells (P< 0.05).

Conclusions: IVCM application provides a strong support to differentiate dry eye patients with different symptoms: meibomian gland dysfunction (MGD) plays a pivotal role in dry eye aggravation, and using IVCM to observe MG fibrosis, changes in size and density of MG as well as status of inflammation cells can help not only correctly diagnose the type and severity of dry eye, but also possibly prognosticate in routine eye examination in the occurrence of MGD.

Figure 1

In vivo confocal microscopy images of meibomian gland morphology changes in the two groups of patients. a, b, and c are from severe symptom group patients. (a) Linear streaks of fibrosis of meibomian gland. (b) Loss of meibomian gland architecture with extensive fibrotic tissue surrounding the atrophic remnants of meibomian gland. White arrows (a and b) point to the areas of fibrosis in meibomian gland. (c) Loss of meibomian gland cell tire-like architecture (as shown in d). White arrows point to meibomian gland acinar units like a thread without normal epithelial cells. (d) Representative image of meibomian gland acinar units with extensive periglandular inflammatory cells in a mild symptom patient.

Figure 2

Comparison of confocal microscopy parameters, Meibomian gland acinar unit density and meibomian gland acinar unit area between the two groups of patients. Meibomian gland acinar units images observed in a representative severe symptom patient (a) and a mild symptom dry eye patient (b). The white arrows depict a typical acinar unit. Quantitative comparison of meibomian gland acinar unit density (c), meibomian gland acinar unit area (d), meibomian gland acinar unit longest diameter (e), and meibomian gland acinar unit shortest diameter (f) between the two groups of dry eye patients. *P < 0.05, t-test. MGAUD: Meibomian gland acinar unit density; MGALD:Meibomian gland acinar unit longest diameter; MGAUA :Meibomian gland acinar unit area; MGASD:Meibomian gland acinar unit shortest diameter.

Figure 3

Alteration of conjunctival inflammatory cell density and Langerhans cell density in the two groups of patients. Representative images of conjunctival inflammatory cell (white arrows) density observed in a severe symptom patient (a) and a mild symptom patient (b). Representative images of Langerhans cells (white arrows) observed in a severe symptom patient (c) and a mild symptom patient (d). Quantitative plots indicating the changes of conjunctival inflammatory cell density (e) and Langerhans cell density (f) between the two symptom patients. *P < 0.05, t-test. CICD: Conjunctival inflammatory cell density.