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Key Facts About Ocular Rosacea
Rosacea is an exceptionally common disease, with some studies estimating that 20% of the population may have this disorder, although the condition remains undiagnosed in many individuals.1 Among patients with rosacea, roughly 60% develop an ophthalmic manifestation of their illness.2 Combining these facts strongly suggests that the ocular impact of rosacea presents a serious epidemiologic burden.
The ophthalmic effects of rosacea can be quite serious and deleterious. Chronic inflammation of the eyelids induces significant periocular aesthetic changes, and patients often report significant eyelid redness and swelling. Additionally, the persistent irritation creates obstruction in the meibomian glands, which stabilize the tear film, and the ocular surface rapidly dries out. Patients are at risk for chronic dryness, infection, and corneal disease. Over time, patients with eye-related rosacea report pain, blurred vision, tearing, and photophobia.
The Role of the Dermatologist and Ophthalmologist
Dermatologists play a key role in the diagnosis and management of ocular rosacea symptoms. Awareness of the ophthalmic consequences of rosacea prompts dermatologists to ask about these symptoms, consider referrals to ophthalmologists, and initiate treatments. Dermatologists may be the first to recognize the ocular effects of rosacea, and the cutaneous treatments initiated by dermatologists may have powerful impacts on the ocular surface.
Optimal management of the ocular surface disease that results from rosacea necessitates a complex interplay between dermatologists and ophthalmologists. A simple slit-lamp examination performed by an ophthalmologist may demonstrate physical findings that are not readily apparent on gross assessment. For instance, meibomian gland plugging, blepharitis, and eyelid margin telangiectasias are easily identified on ophthalmic examination. Any patient with rosacea should be asked about the common ophthalmic symptoms and upon detection of these symptoms, a referral should be made.
Approaches to Treating Ocular Rosacea
Therapeutic approaches work best when dermatologists and ophthalmologists collaborate. Ophthalmologists can often initiate local interventions to heal the ocular surface and improve comfort and vision. Utilize a hierarchical approach to address the eye damage detected. Start with relatively conservative, inexpensive interventions and work toward increasingly aggressive modalities if these initial therapies fail. In the absence of serious corneal pathology (ie, corneal ulcer or nonhealing epithelial defect), start with lubrication, such as artificial tears and ophthalmic ointments. Although topical cyclosporine is designed to improve tear production and patients with rosacea tend to have problems with tear retention, the increased lubrication associated with this medication may help heal the ocular surface. Unfortunately, many symptoms are often not relieved with this approach, and thus treatment tends to move toward other local therapies.
Modalities that release meibum from the glands to stabilize the tear film and improve corneal health can be employed. Peer-reviewed literature strongly supports intraductal meibomian gland probing, which is a relatively low-cost intervention.3,4 Alternatively, vectored thermal pulsation of the glands to release the meibum can be tried.
Nonetheless, rosacea remains a cutaneous ailment, and optimal control of the skin is the gold standard to alleviate ophthalmic disease. Historically, patients were advised to avoid lifestyle factors that may exacerbate the disease, including chocolate, caffeine, alcohol, spicy foods, and sunshine, but most patients cannot adhere to such a rigorous lifestyle.5 The most recent literature does not seem to support a role for ω-3 fatty acid supplements, so I have largely abandoned their use.6,7 Although the use of oral antibiotics remains controversial, they are generally beneficial and should be considered early in the course of patient care to alleviate the cutaneous inflammation.8 Topical local therapies such as metronidazole clearly play some role, although they are not a panacea. Intense pulsed light (IPL) therapy may be performed by either dermatologists or ophthalmologists. Given the adverse effects and cost, IPL requires a highly motivated patient; however, it does appear to be helpful.9
Throughout each step of patient care, close communication between dermatologists and ophthalmologists is critical. Ophthalmologists rely heavily on input from dermatologists about the status of patients’ skin. Although the course of a patient’s ophthalmic disease may not perfectly follow that of the rest of the skin, their responses to local interventions will generally improve with the quiescence of cutaneous inflammation.
Long-Term Treatment Plans
Unfortunately, our treatment armamentarium is not optimal, and patients continue to face a long-term struggle. There are many treatments for rosacea because no single intervention completely addresses the disease. Most of our cutaneous therapies are nonspecific and fail to make the critical distinction between the inflammation in the skin that drives rosacea and the beneficial impacts on the immune system. Alternatively, most local, ocular surface treatments are designed to address damage that has already taken place. For instance, when we ask a patient to begin the use of artificial tears, the goal is to heal dryness on the surface, but the eye findings are simply a manifestation of the disease; we are thus trying to fix damage that is distal to the actual site of the pathology.
Fortunately, the future is bright. Several researchers are working to identify cellular features that distinguish the skin of patients with rosacea from that of people without the disease. Over the past decade, my colleague, Alejandro Adam, PhD, and I have worked to identify specific biologic aberrancies that are inherent to the disease. We believe that delineating these changes may enable us to manipulate them for therapeutic purposes.
Recently, we published our findings that 2 distinct cell signals (p38 and ERK) are enriched in cutaneous specimens of rosacea, and other research groups have since confirmed these findings.10 Based on this result, we developed a cutaneous preparation that selectively suppresses these kinases, and we have initiated a phase 1 trial to explore the role of this skin cream in the management of rosacea. Ideally, by taking a specific cellular approach to target the pathologic inflammation of rosacea, we hope to turn off the disease without interfering with normal cutaneous biology.
Conclusion
Rosacea is an area of intense investigation. Our team and many other research groups have implicated a variety of biologic aberrancies, including moieties such as cathelicidins, toll-like receptors, specific genes, and transcription factors. As clinicians and scientists partner to study this condition, I anticipate that several novel cellular distinctions will be identified, and new therapeutic approaches will arise in response to these findings.
These interventions cannot be developed rapidly enough. Patients are experiencing the pain and vision loss that can be associated with rosacea, and they are frustrated by the lack of highly effective therapies. Although we can often alleviate these symptoms, the effects may not last, and patients must really commit to the treatments. The emphasis on translational research offers the hope of changing the discussion of rosacea management in powerful ways.
References
1. Tan J, Berg M. Rosacea: current state of epidemiology. J Am Acad Dermatol. 2013;69(6 suppl 1):S27-S35. doi:10.1016/j.jaad.2013.04.043
2. Bakar O, Demircay Z, Toker E, Cakir S. Ocular signs, symptoms and tear function tests of papulopustular rosacea patients receiving azithromycin. J Eur Acad Dermatol Venereol. 2009;23(5):544-549. doi:10.1111/j.1468-3083.2009.03132.x
3. Maskin SL. Intraductal meibomian gland probing relieves symptoms of obstructive meibomian gland dysfunction. Cornea. 2010;29(10):1145-1152. doi:10.1097/ICO.0b013e3181d836f3
4. Wladis EJ. Intraductal meibomian gland probing in the management of ocular rosacea. Ophthalmic Plast Reconstr Surg. 2012;28(6):416-418. doi:10.1097/IOP.0b013e3182627ebc
5. Chauhan N, Ellis DAF. Rosacea: pathophysiology and management principles. Facial Plast Surg Clin North Am. 2013;21(1):127-136. doi:10.1016/j.fsc.2012.11.004
6. Dry Eye Assessment and Management Study Research Group, Asbell PA, Maguire MG, et al. n-3 fatty acid supplementation for treatment of dry eye disease. N Engl J Med. 2018;378(18):1681-1690. doi:10.1056/NEJMoa1709691
7. Ziemanski JF, Wolters LR, Jones-Jordan L, Nichols JJ, Nichols KK. Relationship between dietary essential fatty acid intake and meibomian gland dysfunction in postmenopausal women. Am J Ophthalmol. 2018;189:29-40. doi:10.1016/j.ajo.2018.01.004
8. Wladis EJ, Bradley EA, Bilyk JR, Yen MT, Mawn LA. Oral antibiotics for meibomian gland-related ocular surface disease: a report by the American Academy of Ophthalmology. Ophthalmology. 2016;123(3):492-496. doi:10.1016/j.ophtha.2015.10.062
9. Wladis EJ, Aakalu VK, Foster JA, et al. Intense pulsed light for meibomian gland disease: a report by the American Academy of Ophthalmology. Ophthalmology. 2020;127(9):1227-1233. doi:10.1016/j.ophtha.2020.03.009
10. Wladis EJ, Swamy S, Herrmann A, Yang J, Carlson JA, Adam AP. Activation of p38 and ERK mitogen-activated protein kinases signaling in ocular rosacea. Invest Ophthalmol Vis Sci. 2017;58(2):843-848. doi:10.1167/iovs.16-20275
