**1. Introduction**

Dry eye disease is a common condition that causes ocular discomfort [1]. Although it generally does not reduce conventionally tested visual acuity (VA), most individuals with this condition manifest impairment of functional visual acuity, with higher-order aberrations in particular leading to disturbance of quality of vision [2]. Dry eye disease is classified into two major subtypes—aqueous-deficient dry eye (ADDE) and evaporative dry eye (EDE) [3]—both of which can involve pathology of meibomian glands, lacrimal glands, the eyelids, the tear film, and ocular surface cells [4]. ADDE and EDE tend to coexist, in part because the lacrimal gland defects associated with ADDE can lead to meibomian gland dysfunction (MGD) [5], and consequent EDE as a result of friction between the lid margin and the cornea and conjunctiva [6].

Common therapies for patients with ADDE include various topical medications such as cyclosporine, diclofenac sodium, steroids, loteprednol etabonate, resolvin E1, tacrolimus, autologous serum, and vitamin A [7,8]. In addition, punctal plug insertion, oral systemic antibiotics, surgery, dietary modification, local environmental changes, and alternative medicines have been applied [8]. Common therapies for patients with MGD, which is a major cause of EDE, include the application of a warm compress [9], the practice of lid hygiene [9], dietary supplementation with omega-3 fatty acids [9], forced meibum expression [9], intraductal probing [10], automated thermal pulsation [11], and the administration of topical steroids [9], topical and oral antibiotics including topical cyclosporine and azithromycin [9], preservative-free artificial tears [9], lipid-containing eyedrops [9], and topical diquafosol [12,13]. Despite the varied treatment options available, however, some patients with ADDE or MGD are refractory to therapy and therefore do not experience complete or long-term relief of symptoms.

Intense pulsed light (IPL) therapy based on the delivery of intense pulses of noncoherent light with wavelengths of 500 to 1200 nm has been applied in dermatology to treat various conditions, including benign cavernous hemangiomas or venous malformations, telangiectasia, port wine stains, and other pigmented lesions [14,15]. The e fficacy of IPL therapy for patients with dry eye due to MGD was discovered during IPL treatment of facial rosacea [16]. Subsequent studies found that IPL, with or without concomitant meibomian gland expression (MGX), is e ffective for improvement of subjective symptoms and objective findings in patients with mild to moderate MGD or dry eye [17–28]. The combination of IPL and MGX was also shown to be e ffective in patients with refractory MGD [28,29]. In addition, it ameliorated dry eye symptoms and improved meibomian gland function in patients with refractory dry eye, including not only individuals with MGD but also those with graft-versus-host disease or Sjögren syndrome [20] or those with keratoconjunctivitis sicca [30]. However, as far as we are aware, no previous study has evaluated the e ffects of IPL on tear fluid–related parameters in addition to meibomian gland–related parameters in patients with refractory ADDE accompanied by mild MGD. We have therefore now performed a multicenter, retrospective, controlled study to evaluate the e fficacy of IPL combined with MGX in comparison with MGX alone in patients with refractory ADDE and mild MGD who had been treated with conventional therapies.

#### **2. Experimental Section**
