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Current and Emerging Therapies for Ocular Rosacea Medical Management Surgical Therapy 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 Surgical managements in ocular rosacea tend to focus on either enhancing the health of the ocular surface and preventing complications or interventions to address already-existing, severe, vision- and globe- threatening problems. Certainly, punctal occlusion may be employed to improve corneal dryness. 9 Originally described by Maskin, intraductal meibomian gland probing manually opens the scarred glandular orifices, thereby facilitating outflow of the contents and stabilizing the tear film. 20 A recent report documented significant enhancements in ocular surface disease scores with the use of this technique in ocular rosacea patients, 21 although the long-term consequences of this modality remain unknown. 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. US Oph thal mic revie w In order to address existing complications of ocular rosacea, chalazia can be drained in the standard fashion. 9 Severe ocular surface disease that is complicated by corneal thinning may necessitate tissue adhesives, amniotic membrane transplants, and conjunctival flaps, 9 whereas penetrating or lamellar keratoplasties may be utilized to repair corneal perforations. 7 Future Targeted Treatments—Translating Basic Science into Therapy Currently, ocular rosacea is an incurable disease, and, despite the common nature of this disorder, our treatment options are limited and often ineffective. In fact, the aforementioned potential therapies are generally complicated by indirect mechanisms of action (i.e. the uncertain effects of antibiotics on ocular rosacea) that attempt to ameliorate the ocular surface or direct interference with already-existing tissue damage (i.e. probing to repair scarred glands, penetrating keratoplasty to address damaged corneas, etc.) Unfortunately, both variants of therapeutic interventions fail to address the inherent immunologic and molecular biologic aberrancies that ultimately result in ocular rosacea, and, instead, merely serve to mask them. However, as our knowledge of the mechanisms from which rosacea arises increases, existing medications may be employed in novel fashions and new agents may be designed to provide highly selective, targeted therapies for this disorder. Certainly, rosacea has been associated with increased levels of cutaneous microorganisms. 22 Several investigations have explored immunologic aberrancies that may govern host responses to the stimulus of polymicrobial invasion. Specifically, Yamasaki and co-authors identified elevated levels of a family of polypeptides that are specific to leukocyte lysosomes in cutaneous biopsies of rosacea. 23 Similarly, a subsequent series of experiments demonstrated an enrichment of toll-like receptor-2 in skin biopsies of rosacea patients. 24 The toll-like receptors are a family of membrane-spanning proteins that provide surveillance against tissue damage and invading pathogens, and, upon detection, initiate and coordinate responses to clear these pathogens and/or repair the tissue. 25 Additionally, Casas and colleagues reported increased expression of genes encoding interleukin-8 and -1b, tumor necrosis factor-a, and inflammasome-related genes (NALP-3 and CASP-1) 26 in the skin of rosacea patients compared with normal controls. Selective interference or manipulation of these receptors, polypeptides, and molecules might represent novel mechanisms to reduce the pathologic inflammation associated with rosacea. Nonetheless, the ocular variant of this disease was selectively excluded from these studies, thereby complicating the applicability of these fascinating results to the management of rosacea’s ophthalmic manifestations. 87