Corneal Nerve Abnormalities in Painful Dry Eye Disease Patients.

Adrian Guerrero-Moreno,Ghislaine Rabut,Stéphane Melik Parsadaniantz,Christophe Baudouin,Hong Liang,Antoine Labbé,Annabelle Réaux-Le Goazigo,Nathan Moreau,Jade Luzu

doi:10.3390/biomedicines9101424

Abstract

Background: This study aimed to compare the corneal nerve structural abnormalities detected using in vivo confocal microscopy (IVCM) in patients with neuropathic corneal pain (NCP) secondary to primary meibomian gland dysfunction (MGD) or autoimmune dry eye (AIDE). Methods: A two-stage retrospective nested case–control study was conducted. First, data from patients with either MGD or AIDE were assessed, selecting only cases with no corneal pain (VAS = 0) or severe pain (VAS ≥ 8). Ocular signs and symptoms of the 238 selected patients were compared between painful and painless cases. Next, painful patients with no corneal damage (Oxford score ≤ 1) were selected within each study group, defining the cases with NCP (i.e., “pain without stain”). IVCM images from all groups were compared with prospectively-recruited healthy controls, focusing on dendritiform cell density and nerve abnormalities (density, tortuosity, microneuromas). Results: AIDE patients had more ocular signs/symptoms than MGD patients. Compared with healthy controls, AIDE-related NCP patients showed increased nerve tortuosity and number of neuromas, whereas MGD-related NCP patients had reduced nerve density and increased number, perimeter, and area of microneuromas. Microneuromas were also observed in healthy controls. Furthermore, a higher number of microneuromas was found in MGD-related NCP compared to AIDE-related NCP or painless MGD. Conclusions: MGD-related NCP was associated with significantly more corneal nerve abnormalities than AIDE-related NCP or healthy controls. Although IVCM can be useful to detect NCP-related corneal nerve changes in such patients, the diagnosis of dry eye disease-related NCP will require an association of several IVCM-based criteria without relying solely on the presence of microneuromas.

Highlights

Dry eye disease (DED) is “a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles”, as defined in 2017 by the TFOS Dry
To further elucidate the various corneal nerve changes associated with dry eye diseases, a retrospective nested case–control study was performed to assess the clinical features of patients suffering from primary meibomian gland dysfunction (MGD) and Autoimmune dry eye (AIDE) and severe corneal pain, compared with their respective painless counterparts
Ultrastructural corneal characteristics were studied among patients presenting neuropathic corneal pain (NCP) characteristics and compared with their painless counterparts and healthy volunteers

Summary

Introduction

Dry eye symptoms are among the most frequent complaints observed in general ophthalmological practice. They include visual disturbances, discomfort, and pain. Ocular signs and symptoms of the 238 selected patients were compared between painful and painless cases. Painful patients with no corneal damage (Oxford score ≤ 1) were selected within each study group, defining the cases with NCP (i.e., “pain without stain”). AIDE-related NCP patients showed increased nerve tortuosity and number of neuromas, whereas MGD-related NCP patients had reduced nerve density and increased number, perimeter, and area of microneuromas. Conclusions: MGD-related NCP was associated with significantly more corneal nerve abnormalities than AIDE-related NCP or healthy controls. IVCM can be useful to detect NCP-related corneal nerve changes in such patients, the diagnosis of dry eye disease-related

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