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Current and Emerging Therapies for Ocular Rosacea

US Ophthalmic Review, 2013;6(2):86–8 DOI: http://doi.org/10.17925/USOR.2013.06.02.86

Abstract:

Ocular rosacea is an incurable disease that affects millions of Americans annually. While multiple therapeutic strategies have been devised to address this disorder (including topical and oral medications, laser and light-based treatments, and surgical interventions), our current interventions are largely nonspecific and often ineffective. Nonetheless, ocular rosacea remains a source of intense research, and newer treatments offer tremendous promise for improved outcomes. In this review, we discuss the current and emerging treatment modalities for ocular rosacea and analyze novel basic science findings that will hopefully lead to highly targeted medications to treat this potentially blinding illness with greater specificity and fewer side effects.
Keywords: Ocular rosacea, ocular surface, toll-like receptor, cytokine, arteriole, intraductal meibomian gland probing, dry eye disease
Disclosure: The authors have no conflicts of interest to declare.
Received: July 22, 2013 Accepted: August 08, 2013
Correspondence: Edward J Wladis, MD, FACS, Ophthalmic Plastic Surgery, Department of Ophthalmology, Lions Eye Institute, Albany Medical College, 1220 New Scotland Rd, Suite 302, Slingerlands, NY, 12159, US. E: tedwladis@gmail.com

Ocular rosacea is an incurable disorder that results in significant inflammation of the eyelids and ocular surface,1,2 and patients that suffer from this disorder are at increased risk for pain, photophobia, infection, and vision loss.3–7 While specific estimates of the total number of patients with ocular rosacea vary considerably, over 16 million Americans are affected by acne rosacea,8 and 58–72 % of rosacea patients develop ophthalmic findings.9

Despite the relatively common nature of ocular rosacea and its severe potential consequences, this disease remains difficult to treat, and disease stabilization remains elusive.

In this article, we discuss new treatment strategies for the management of ocular rosacea and outline emerging basic science findings aimed at providing targeted, highly selective therapies for this frustrating, common ailment.

Current Disease Management
Our lack of understanding of the molecular and immunologic mechanisms responsible for the onset of rosacea force us to treat patients with an array of nonspecific, less-than-optimal therapeutic strategies to minimize ocular damage. We can separate these into three main categories: the avoidance of triggers, to reduce the exposure of the ocular surface to the disease; conservative measures to minimize the damage caused by rosacea and alleviate active symptoms; and therapies to revert the damage that has already occurred.

Avoidance of Triggers
While rosacea is a persistent inflammatory condition, the ophthalmic manifestations of this disorder are often exacerbated by multiple triggers. The ingestion of alcohol, caffeine, chocolate, cheese, and specific medications have all been linked to worsening rosacea,7 and astringent cutaneous preparations have been reported as possible pro-inflammatory agents.10,11 Finally, prolonged sunlight exposure,extreme weather conditions, and physical and emotional stresses may all inflame the skin of patients with rosacea.7 As such, after diagnosis, patients should be cautioned of the importance of these triggers, and should avoid them, as necessary, although the specific factors vary from patient to patient.

Conservative Measures
Given the association between ocular rosacea, meibomian gland dysfunction (MGD), and ocular surface disease,12 patients with the cutaneous manifestations of ocular rosacea frequently develop severe blepharitis and subsequent corneal dryness and conjunctival irritation. Conventionally, the mainstay of care has been to address the manifestations of the underlying ocular rosacea with eyelid hygiene. Specifically, warm compresses are applied to the eyelids, with the intent of unclogging the meibomian glands, improving the outflow of their contents, and stabilizing the tear film. Digital massage may also be employed to liberate the meibomian gland contents, and eyelid scrubsare used to remove the crusting along the eyelids.13

Medical Management
Medical management with topical agents is indicated in mild cases of ocular rosacea with MGD. In order to address the ocular surface dryness inherent to ocular rosacea, artificial tears and lubricating ointments have been utilized to heal defects in the corneal epithelium. Additionally, nutritional supplementation with fish oil and flax seed has been reported to improve the symptoms of blepharitis and meibomian gland disease.13 Furthermore, topical cyclosporine has been reported to improve ocular surface disease index scores, corneal staining patterns, and tear-production levels.14 More advanced cases of ocular rosacea generally necessitate oral therapeutics, although the mechanisms of action of many of these medications are unclear and often nonspecific. Several lines of evidence have demonstrated increased levels of Demodex Folliculorum on the skin of patients with rosacea compared with normal controls. While oral antibiotics remain the mainstay of care, considerable controversy surrounds the matter of whether the improvement in the ocular surface is due to the antimicrobial properties of these agents (i.e. decreasing pathogenic flora) or their anti-inflammatory and anti-angiogenic utilities. In either case, oral tetracycline (initiated at 500 mg, twice daily for several weeks, and then gradually decreased in a fashion that is titrated to clinical response), oral doxycycline (100 mg, once or twice daily), or a combination of a 30 mg dose of standard oral doxycycline and 10 mg of sustained-release oral doxycycline have all shown significant benefits in the treatment of this disorder.9,12,15 Nonetheless, these medications require prolonged use and are associated with the standard risks inherent to long-term ingestion of antibiotics (including infection, multidrug resistance, gastrointestinal distress, allergy, photosensitivity, and other problems), thus raising the need for more targeted systemic therapeutics that can be tolerated for prolonged periods.

Laser and Light-based Therapies
Laser and light-based therapies have recently emerged as possible therapeutic alternatives in the management of cutaneous rosacea. Given the ability to selectively target vascular lesions, these modalities have been employed to address multiple facial lesions with excellent results. Intense pulsed light (IPL) involves the application of noncoherent wavelengths of light to affected regions of the skin, whereas laser provides a single wavelength to the skin. With either modality, the light energy is absorbed by oxyhemoglobin and converted to thermal energy, ultimately resulting in photocoagulation, thermal injury, and, ultimately, thrombosis.16

Papageorgiou and co-authors reported dramatic improvements in erythema, facial telangiectasias, and clinical severity after four treatments with IPL.17 Similarly, Schroeter and colleagues documented significant, durable reductions in facial telangiectasias with the use of IPL.18 In addition, Shim et al. demonstrated marked improvements in quality of life after treatment with pulsed dye laser.19 Nonetheless, treatment of periocular skin was specifically excluded from these studies, making the applicability of these results to ocular rosacea somewhat difficult. Besides the obvious risk for damaging the retina using lasers or other strong sources of light, it is unclear whether this treatment would affect meibomian gland function or merely reduce the extent of the erythema without preventing corneal damage. Future investigations should explore the utility and safety of these interventions in the management of ocular rosacea.

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Keywords: Ocular rosacea, ocular surface, toll-like receptor, cytokine, arteriole, intraductal meibomian gland probing, dry eye disease