In vivo confocal microscopy in dry eye disease and related conditions

Abstract

A new era of ocular imaging has recently begun with the advent of in vivo confocal microscopy (IVCM), shedding more light on the pathophysiology, diagnosis, and potential treatment strategies for dry eye disease. IVCM is a noninvasive and powerful tool that allows detection of changes in ocular surface epithelium, immune and inflammatory cells, corneal nerves, keratocytes, and meibomian gland structures on a cellular level. Ocular surface structures in dry eye-related conditions have been assessed and alterations have been quantified using IVCM. IVCM may aid in the assessment of dry eye disease prognosis and treatment, as well as lead to improved understanding of the pathophysiological mechanisms in this complex disease. Further, due to visualization of subclinical findings, IVCM may allow detection of disease at much earlier stages and allow stratification of patients for clinical trials. Finally, by providing an objective methodology to monitor treatment efficacy, image-guided therapy may allow the possibility of tailoring treatment based on cellular changes, rather than on clinical changes alone.

FIGURE 1

Cornea epithelial layer in normal and dry eye patients. Normal subjects: (A) normal superficial epithelium with few hyperreflective cells (squamous metaplasis) and dark nuclei; (B) intermediate wing layer with symmetrical shape, bright cell borders and dark cytoplasm; (C) regularly arranged small cells with bright borders and non-homogenous cystoplasmic reflectivity. Dry eye patients: (D–F) epithelial squamous metaplasia (hyperreflectivity) with increase in desquamation, enlarged cells, pyknic nuclei, and lower cell density as compared to normal.

FIGURE 2

In vivo confocal images of cornea sub-basal nerve plexus, dendritic cells, and stromal keratocytes. (A) Central and (C) peripheral sub-basal nerve plexus demonstrating normal pattern with few denditriform cell; (B) central and (D) periphery images showing loss of nerves and increase in dedritiform cell density in dry eye patients. Stroma (E) with bright oval keratocyte nuclei and (G) stromal nerves; (F) and (H) dry eye subjects with keratocyte pleomorphism (potentially immune cells), more tortuous nerves, and decreased nerve density.

FIGURE 3

In vivo confocal images of the lid and meibomian glands. (A) Meibomian gland orifice in normal patient and (B) closed orifice in a patient with meibomian gland dysfunction (MGD). Tarsal conjunctiva of normal subject (C). Conjunctiva shows increase in inflammatory cells in MGD patient (D) as compared to normal subject (C). Acinar meibomian gland units (E) with few hyperreflectivity areas; MGD patient with decreased acinar density, atrophic morphology, and increase in hyperreflective areas (F).