Ocular Rosacea: Curse of the Celts and Celebs

The presentation is given by Heather Potter, MD, an Ophthalmologist from the University of Wisconsin School of Medicine and Public Health.

Highlights

Some of the points that I thought were interesting;

• rosacea is not purely related to demodex mites because eradicating them with Lindane (quite a dangerous drug it seems) does not help rosacea symptoms.
• some good slides and description of the life cycle of demodex
• tea tree oil shampoo for lid hygiene as in normal blepharitis treatment is a good option for demodex infestation of the eyelid.
• Tea Tree Oil is the best treatment we have for demodex
• Tea Tree Oil 20% combined with macadamia or walnut oil is another option
• Otophyma gets a mention, with a slide where you are directed to the visible pores in the enlarged ear
• Azelaic Acid 20% is mentioned at a 1st line topical treatment, but I think they actually meant Finacea which is only 15%
• Sodium Sulfacetamide wash as a lid scrub is mentioned as an alternative to baby shampoo
• “Burst and Taper” or just starting out with 40mg a day of doxycycline is mentioned as an oral treatment
• 3000 – 4000 mg Omega 3, tapering to 2000 mg a day maintenance has worked well for her ocular rosacea patients. It takes 6 weeks to have an effect.
• Ocular rosacea is found equally in males and females.
• Cyclosporin gets a mention as a topical treatment. Azasite Plus drops (a steroid plus azithromycin) is shown on the topical treatments slide.
• Need to raise the body temperature by 5 degrees before attempting warm compresses to liquify the meibomian gland secretions you are trying to clean.
• Cyclosporin gets another mention for dry eyes, along with punctal plugs
• Doxycycline gets a mention specifically as an ocular rosacea treatment
• An image from a “throw away journal” with what looks like a device to heat and massage the eyelids to help clear the glands.

The video is 25 minutes long, but you can squash it down to 16 minutes if you select the 1.5x link at the bottom of the video player.

Well worth a watch.

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What bit of the video was most worthwhile for you?

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Currently there is no definitive diagnostic test for ocular rosacea, it is based on clinical symptoms. One proposed diagnostic test is high abundance of oligosaccharides in the tear fluid of patients with rosacea.

Definitions

Schirmer Test: determines whether the eye produces enough tears to keep it moist.

TBUT: Tear Break up Time, the time required for dry spots to appear on the corneal surface after blinking.

Abstract

Clinical and laboratory study of ocular rosacea in northern Greece.

Lazaridou E, Fotiadou C, Ziakas N, Giannopoulou C, Apalla Z, Ioannides D., J Eur Acad Dermatol Venereol. 2011 Mar 2.

First Departments of Dermatology-VenereologyOphthalmology, Aristotle University Medical School, Thessaloniki, Greece.

Background: The prevalence of ophthalmic involvement in rosacea is probably higher than previously presumed and varies considerably among several studies. Objective This study aimed to determine the incidence of ocular disease among a population of rosacea patients in Northern Greece, to objectively determine the presence of eye dryness in rosacea patients with and without clinical ophthalmic involvement and correlate the severity of ocular disease with the severity of cutaneous rosacea.

Methods: One hundred patients with rosacea were assessed for the stage of their disease and examined for ocular symptoms and signs. In 24 of them the tear break up time (TBUT) and Schirmer test were performed in each eye, along with 24 controls.

Results: A total of 33 patients (33%) were positive for ophthalmic findings. The most frequent symptoms and signs were burning sensation and tearing, and conjunctivitis and blepharitis, respectively. Eleven patients with ophthalmic manifestations had mild to moderate erythematotelangiectatic rosacea, 17 had moderate papulopustular rosacea and four exhibited findings of phymatous rosacea. The total mean value of patients’ Schirmer tests was significantly lower compared with the healthy controls (P < 0.0001). Mean TBUT was shorter in the rosacea group than that in the age-matched controls (P < 0.0001).

Conclusion: Ocular involvement in rosacea is a common phenomenon with eye dryness being an early sign. Tear function tests, like Schirmer test and TBUT, although not specific, could contribute to the screening and early diagnosis of the disease, to prevent the potential development of sight-threatening conditions.

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Itchy, sandy feeling in eyelids may be blepharitis

Question: What causes my eyelids to be itchy and sandy in the mornings?

Answer: The most likely cause of your symptoms is something called blepharitis, or inflammation of the eyelids, and is the most common ocular disease we see. This type of inflammation is sometimes, but not always, associated with a bacterial infection, dry eyes, or a skin condition such as acne rosacea.

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Common symptoms may include the scratchy sensation of a foreign body, or burning, flaking, tearing, crusting, itching, inflammation and redness of the lid margins.

Dry eye syndrome may be associated with either type and may make the symptoms worse. Allergic sources, smoke, dust or a dry environment, while not a cause of this problem, can also contribute to the severity of symptoms. The uncertain cause, chronic nature of the associated conditions, and inadequate treatments make this condition difficult to manage.

Given the number of possible causes and symptoms, the actual diagnosis in your case requires a good eye examination by your ophthalmologist.

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Taking fish oil capsules may be helpful by making the oily secretions less thick and allowing them to flow out of the glands more freely.

It is important to understand that blepharitis is often a chronic condition requiring ongoing attention in order to reduce symptoms over time. However, good eyelid hygiene and prescription medications are often effective at managing the symptoms of this disease.

Dr. Donald Lewellen Jr. is a board-certified ophthalmologist at Eye Clinic of Manitowoc and the Two Rivers Eye Clinic.

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Timolol has been used orally in the treatment for hypertension and opthalmic solutions have been used to reduce intraocular pressure in glaucoma.

Clinical Trial NCT01250457: Topical Timolol for the Treatment of Benign Vascular Periocular Lesions

Pre-treatment and post-treatment lesion size will then be compared to determine whether twice-daily topical application of timolol 0.5% solution alters the morphometry of benign vascular periocular lesions.

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Benign vascular tumors of the eyelid are common causes of ocular morbidity. Capillary hemangiomas in children cause refractive and occlusive amblyopia. In adults, Rosacea-associated eyelid telangiectasis and sclerosis can result in keratitis and corneal neovascularization.

Corticosteroid therapy of benign vascular lesions risks sight-threatening complications including central retinal artery occlusion and significant systemic morbidity.

Alternatively, oral and intravenous beta-blockers have been reported to induce regression of benign vascular lesions. One recent report documented efficacy of topical timolol in treating a large capillary hemangioma of the eyelid in a child.

Topical application reduces systemic side effects of beta-blockers including bradycardia, hypotension, heart block, and bronchospasm. This one-year prospective case-control series will investigate whether topical Timolol 0.5% solution applied twice daily causes significant regression of benign vascular periocular lesions.

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Mites and Eye Symptoms

A new study has found there may be a link between ocular rosacea and bacteria associated with Demodex mites, microscopic inhabitants of normal skin that tend to occur in much greater numbers in those with rosacea.

In the recently published study of 59 rosacea patients, Dr. Jianjing Li and colleagues at the Ocular Surface Center in Miami found a significant correlation between facial rosacea, infestation of the eyes with Demodex mites and reaction to certain mite-related organisms previously shown to stimulate an immune response in rosacea sufferers.

Rosacea News covered this paper in April and resulted in a similar summary;

Ocular symptoms match Demodex Bacteria reaction too

This paper is one more small achievement using statistics to try to build a picture of how demodex mites might be involved with rosacea symptoms. We have learnt from recent research that rosacea sufferers are sensitive to 2 particular types of bacteria that have been isolated in demodex mites.

This study further establishes that a reaction to the bacteria correlates to ocular symptoms as well as facial symptoms.

So the small step forward is that for those with rosacea linked to demodex bacteria, ocular symptoms may also be exacerbated by a reaction to the bacteria.

As the NRS Blog notes, more research may help draw out exactly how strongly demodex bacteria and facial and ocular rosacea symptoms are related to each other.

Related Articles

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This study further establishes that a reaction to the bacteria correlates to ocular symptoms as well as facial symptoms.

So the small step forward is that for those with rosacea linked to demodex bacteria, ocular symptoms may also be exacerbated by a reaction to the bacteria.

Correlation between Ocular Demodex Infestation and Serum Immunoreactivity to Bacillus Proteins in Patients with Facial Rosacea, Ophthalmology. 2010 Jan 14, Li J, O’Reilly N, Sheha H, Katz R, Raju VK, Kavanagh K, Tseng SC..

PURPOSE: To investigate correlation between ocular Demodex infestation and serum.

DESIGN: A prospective study to correlate clinical findings with laboratory data.

PARTICIPANTS: We consecutively enrolled 59 patients: 34 men and 25 women with a mean age of 60.4+/-17.6 years (range, 17-93).

METHODS: Demodex counting was performed based on lash sampling. Serum immunoreactivity to two 62-kDa and 83-kDa proteins derived from B oleronius was determined by Western blot analysis. Facial rosacea, lid margin, and ocular surface inflammation were documented by photography and graded in a masked fashion.

MAIN OUTCOME MEASURES: Statistical significance based on correlative analyses of clinical and laboratory data.

RESULTS: These 59 patients were age matched, but not gender matched, regarding serum immunoreactivity, ocular Demodex infestation, or facial rosacea. There was a significant correlation between serum immunoreactivity and facial rosacea (P = 0.009), lid margin inflammation (P = 0.040), and ocular Demodex infestation (P = 0.048), but not inferior bulbar conjunctival inflammation (P = 0.573). The Demodex count was significantly higher in patients with positive facial rosacea (6.6+/-9.0 vs. 1.9+/-2.2; P = 0.014). There was a significant correlation of facial rosacea with lid margin inflammation (P = 0.016), but not with inferior bulbar conjunctival inflammation (P = 0.728). Ocular Demodex infestation was less prevalent in patients with aqueous tear-deficiency dry eye than those without (7/38 vs. 12/21; P = 0.002).

CONCLUSIONS: The strong correlation provides a better understanding of comorbidity between Demodex mites and their symbiotic B oleronius in facial rosacea and blepharitis. Treatments directed to both warrant future investigation

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Dr. Mannis in his interview for the RSRP had this to say about IPL and ocular rosacea.

Q: Do you think IPL treatment of the face usually improves ocular rosacea? What about patients who feel that it has made their ocular rosacea worse, eg more veins showing in the white of the eye, lids more sensitive, eyelashes falling out, hot compresses now cause the eyes to swell?

A: Unfortunately, as ophthalmologists, we have very little experience with IPL. That’s something that’s done by and large by dermatologists. I am not aware of any definite ocular side effects from facial treatments with IPL.

Q: Does ocular rosacea increase the likelihood of cataracts or other eye diseases such as macular degeneration, or central serrous corinopathy (retinopathy)?

A: No. But, if IPL is done, there needs to be eye protection. Any kind of laser treatment done on the skin around the eye requires the practitioner to use eye shields to be sure that the globe is not exposed to the intense light in any way. As long as it’s not, then the likelihood of any of those problems occurring is very small.

For more information on Dry Eye see the following articles: Dry Eye: Awareness, Diagnosis, and Management and Dry Eye Syndrome from Sunday Times Sri Lanka

Zapping Dry Eye

Posted: 12:23 pm EDT October 8, 2009

Christopher Coad, M.D., Ophthalmologist at Chelsea Eye & Cosmetic Surgery Associates in New York City, is using a technique for some dry eye patients called intense pulsed light therapy (IPL). IPL is sometimes used to reduce facial skin redness caused by growth of abnormal blood vessels in patients with rosacea. Doctors noticed that some rosacea patients reported easing of dry eye symptoms after getting IPL. That finding led physicians to try it for patients with dry eye.

First, eye shields and a cooling ultrasound gel are placed around the eyes to protect the eyes and surrounding skin. Then, the IPL is aimed under the lower lid, moving across the eyes. Two passes of the light are made. Then the gel and eye shields are removed.

Coad says IPL has three main effects on dry eye. First, the heat acts like a warm compress to liquefy the blocked oil that’s plugging the meibomian gland. Second, the small blood vessels that carry inflammatory cells to the site are sealed. Third, the light treatment improves the health and function of the meibomian gland, reducing the risk of further inflammation.

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Elidel no better than Metrogel for lumps and bumps of rosacea.

A comparison of metronidazole 1% cream and pimecrolimus 1% cream in the treatment of patients with papulopustular rosacea: a randomized open-label clinical trial. Clin Exp Dermatol. 2009 Jul 6

Patients were randomly assigned treatment with either pimecrolimus 1% cream or metronidazole 1% cream for 12 weeks. Pimecrolimus cream is no more efficacious than metronidazole cream in the treatment of PR.

Another bacterial link found ?

Is rosacea another disorder of gut microbes? Curr Gastroenterol Rep. 2009 Aug;11(4):253-4

This paper sounds like it might be heading in the direction to add to some research that looks at small intestinal bacterial overgrowth as a source of rosacea symptoms. Alas all we can see at the moment is the title. Also note that the author has published several other papers that at least in their title link intestinal disorders with diseases such as fibromyalgia as obesity.

Facial blood vessels correlate to Ocular Rosacea Symptoms

This paper, who’s full text is available via the link, suggests that the presence of facial visible blood (telangiectasia) is more of a clue that ocular rosacea may also be present, compared to other facial symptoms like papules and pustules.

Correlation of the severity of cutaneous rosacea with ocular rosacea,  Indian J Dermatol Venereol Leprol 2009;75:405-6.

In our series, ocular involvement did not correlate with the severity of papular, pustular, nodular lesions and flushing but, surprisingly, we found a significant relationship between the severity of telangiectasia and ocular involvement. This finding was not in agreement with the previous studies claiming that the ophthalmologic complications of rosacea are completely independent of the severity of facial rosacea. On the other hand, it seems that the significant relationship between the severity of telangiectasia and eye lesions in our study might be an incidental experience. We agree with the general assumption that skin and eye lesions in rosacea are separate al together.

IAP the link from intestine to Rosacea Skin ?

This paper is proposing that the activity of the enzyme intestinal alkaline phosphatase (IAP) could be the link between an inflammatory response to intestinal bacteria and rosacea skin symptoms.

Intestinal alkaline phosphatase: The molecular link between rosacea and gastrointestinal disease?, Med Hypotheses. 2009 Jun 30 (UMR 168 CNRS/Institut Curie, 11 rue Pierre et Marie Curie, 75005 Paris, France Rosacea Research and Development Institute, Pahala HI 96777, USA)

Rosacea is a common inflammatory condition of the facial skin of unknown etiology, which frequently occurs in combination with gastrointestinal disorders. Many dietary and hormonal factors are known to affect the severity of rosacea symptoms, several of which also modulate the activity of the enzyme intestinal alkaline phosphatase (IAP). The role of IAP in inhibiting an inflammatory response to intestinal bacteria suggests a mechanism by which intestinal pathologies may be linked to the skin inflammation characteristic of rosacea. Analysis of alkaline phosphatase activity is routinely performed on blood samples, and methods to quantify enzyme activity of the intestinal isoform specifically have been described. Correlations between IAP activity and rosacea symptoms in patients and controls can thus be screened by noninvasive and inexpensive means. If IAP activity is found to be low in rosacea patients, acute symptoms could be treated with oral IAP supplementation, and trials of IAP-activating medications currently used in gastrointestinal disease could be initiated in rosacea patients. More importantly, the safe and long-term control of rosacea could be undertaken by patients themselves through dietary modification to naturally increase IAP activity.

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It is good to see more published research backing topical cyclosporine (Restasis, Allergan) as a treatment for ocular rosacea. Restasis (cyclosporine ophthalmic emulsion 0.05%) has been shown to increase tear production and improve the quality of naturally produced tears and is the first approved therapeutic agent for the treatment of chronic dry eye.

Official Use of Restasis

The FDA has approved Restasis as a treatment to increase tear production in patients whose tear production is presumed to be suppressed due to ocular inflammation associated with chronic dry eye. Note that increased tear production was not seen in patients currently taking topical anti-inflammatory drugs or using punctal plugs. Restasis is not appropriate for immediate relief for an uncomfortable irritated eye as it may take up to 6 months for maximum improvement. (source The Eye Digest)

Other Evidence

An article from 2006 in Ophthalmology Management Topical cyclosporine proves to be effective in treating rosacea whetted our appetite for this interesting new treatment.

The anti-inflammatory mechanisms of cyclosporine are highly appropriate for the treatment of ocular rosacea, as the condition has been shown to have an inflammatory etiology. Barton and associates conducted a study comparing tear fluid concentrations of interleukin-1alpha (IL-1alpha) and tumor necrosis factor-alpha (TNF-alpha) in ocular rosacea with those in control subjects. Tear turnover was lower in patients with rosacea than in controls, and Schirmer scores were also statistically lower in patients with rosacea than in controls.

After 6 months of use, topical cyclosporine was shown to decrease inflammatory cytokines in the conjunctival epithelium of dry eye patients with increased tear production.

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Given the excellent side effect profile of topical cyclosporine and its lack of systemic absorption, ophthalmologists should consider utilizing topical cyclosporine in the treatment of patients with ocular rosacea.

Expert Opinion

The Rosacea Support Group asked Dr. Eric Jones, MD, the Medical Director of Devers Eye Institute in Portland, Oregon a related question about Restasis and ocular rosacea.

Q: Do you agree with the view that Restasis won’t help ocular rosacea or dry eye triggered by Accutane?

A: The drug rep was in for Restasis the other day and I asked her about it. We looked it up here and didn’t find any studies that checked on Restasis and ocular rosacea together. It’s a great question because, you know people with ocular rosacea have decreased tear production and, if Restasis can help that, I don’t see why it wouldn’t work.

Recent Abstract

Below is the abstract from the recently published paper, from the same author as the above article, but now appearing in a peer reviewed journal. The above link to Ophthalmology Management leads to a full article, which can be consulted for more details if you don’t have access to the full text of the journal article.

Efficacy of topical cyclosporine for the treatment of ocular rosacea, Adv Ther. 2009 Jun 23, Schechter BA, Katz RS, Friedman LS, Florida Eye Microsurgical Institute.

INTRODUCTION: This study was designed to compare the efficacy of cyclosporine ophthalmic emulsion 0.05% with an artificial tear solution for the treatment of rosacea-associated eyelid and corneal pathology.

METHODS: Double-masked, randomized, 3-month clinical trial of 37 patients with rosacea-associated eyelid and corneal changes (defined as lid margin telangiectasia, meibomian gland inspissation, and/or fullness of the lid margin). All findings were standardized and compared to photographs for grading.

RESULTS: There was a statistically significant increase in Schirmer (with anesthesia) scores of 2.7+/-2.2 mm after 3 months of treatment in the topical cyclosporine group (P<0.001), compared with a mean decrease of -1.4+/-4.6 mm (P=0.271) in the artificial tears group. The mean tear break-up time score significantly improved in the topical cyclosporine group (mean increase of 3.56+/-1.5 seconds, P<0.001), but worsened in the control group, although this change was not significantly significant (mean decrease of -0.04+/-1.6 seconds, P=0.929). The topical cyclosporine group exhibited a significantly greater mean reduction in corneal staining scores (-1.3+/-0.53) compared with the control group (-0.2+/-0.83; between groups P<0.001). The topical cyclosporine group had a greater improvement in Ocular Surface Disease Index scores than those using artificial tears (P=0.022). Limitations of the study included an older, predominantly Caucasian patient population and short trial length.

CONCLUSIONS: Topical cyclosporine 0.05% is more effective than artificial tears for the treatment of rosacea-associated lid and corneal changes.

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One of inventors of this patent is well known to rosacea sufferers. Dr. Mark Mannis has been friendly and helpful to online rosacea sufferers, see his interview – Ocular Rosacea: Dr. Mark J. Mannis, MD. He has also been mentioned in Rosacea News in the past; wearing contact lenses and ocular rosacea and was a contributor to the standard classification of rosacea.

Rosacea News first highlighted a possible diagnostic test for ocular rosacea in late 2005. The journal article from the Journal of Proteome Research concluded that “The high abundance of oligosaccharides in the tear fluid of patients with rosacea may lead to an objective diagnostic marker for the disease.”

An objective diagnostic test for ocular rosacea would be an excellent achievement for rosacea sufferers. Being able to be definitively diagnosed with ocular rosacea, especially if no other other rosacea symptoms are present, will enable those sufferers to seek immediate treatment. As we all know an accurate diagnosis is almost the most important step in getting better.

United States Patent Application 20090118141, May 7, 2009. METHODS OF OLIGOSACCHARIDE PROFILING FOR THE DETECTION OF OCULAR ROSACEA, Lebrilla; Carlito B.; (Davis, CA) ; An; Hyunjoo; (Davis, CA) ; Alvarenga; Lenio S.; (Sao Paulo, BR) ; Mannis; Mark D.; (Carmichael, CA)

The present invention provides methods for identifying oligosaccharides specific to an inflammatory or infectious disease, methods for diagnosing an inflammatory or infectious disease by detecting the presence or absence of such oligosaccharides, and methods for treating an inflammatory or infectious disease by administering antibodies directed to such oligosaccharides. The present invention also provides methods for diagnosing ocular rosacea by determining the presence or absence of specific oligosaccharide markers. In addition, the present invention provides markers for ocular rosacea comprising 0-linked oligosaccharides as well as kits for diagnosing or treating ocular rosacea.

The patent raises the possibility of an ocular rosacea treatment that uses “a therapeutically effective amount of an antibody that binds specifically to a unique oligosaccharide”. This suggests that a new class of rosacea treatments might arise from this invention.

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