ocular rosacea by sandra cremers, md

A Hidden Concern in Ocular Rosacea

Sandra Lora Cremers, MD, FACS

March 2013

THUMP!

Rosacea, Boring and Not Glamorous?

1. Describe Epidemiology, Diagnosis, Pathophysiology, and Treatment of Rosacea and Ocular Rosacea

2. Discuss Recent Research Finding of Rosacea and Ocular Rosacea

3. Discuss Ocular Rosacea's Relationship to other Angiogenesis Based Diseases

Objectives:

1. Case Presentations

2. Diagnosis and Details

3. Observations & Collaborations

4. A Hidden Concern

Outline:

1. Case Presentations

79 yo white male presents complaining of "poor vision in right eye after cataract

surgery. Worse than before the surgery"

Case Presentation:

BCVA: 20/50 OD, 20/30 OSExternal exam:

Case Presentation:

R

Unhappy patient because he perceived a missed diagnosis of

ocular rosacea as the reason for less than expected vision after cataract

surgery.

Ultimate Diagnosis:

A Brief Historical Perspective

Young Rembrandt Older Rembrandt

2. Diagnosis and Details

Rosacea is a multifactorial, hyper-reactivity, vascular and neural based disease with a broad range of facial and manifestations where normal vasodilation is greater and more persistent and involves an autoimmune component where microscopic amounts of extravasated plasma induce localized dermal inflammation where repeated external triggers lead vasodilation, telangiectasias, redness with eventual fibrosis and hypertrophic scarring of the dermis.

A Definition of Rosacea

Subtypes of ROSACEA

What is Ocular Rosacea and How do you make the

Diagnosis?

1. In 3-58% of patients with Rosacea2. M=F3. European descent more common4. Starts in 20's and often worsens with age 5. Can be seen in kids

Epidemiology of Ocular Rosacea:

1. Burning2. Foreign body sensation3. Dry eye4. Tearing (reflex)5. Eye redness6. Mattering of eyelids

Symptoms:

1. Blepharitis & MGD2. Lid margin telangiectasia3. Conjunctivitis4. Recurrent chalazia5. Corneal pannus6. SPK7. Episcleritis, Scleritis (not common)8. Interstitial keratitis & residual corneal scarring

Signs:

1. Blepharitis & MGD2. Lid margin telangiectasia3. Conjunctivitis4. Recurrent chalazia5. Corneal pannus6. SPK7. Episcleritis, Scleritis (not common)8. Interstitial keratitis & residual corneal scarring

Signs:

Pathophysiology

Many Theories of Ocular Rosacea

Chemicals

Ingested Agents Climatic Exposures

Microbial

Bacillus oleronius

Demodex

Vascular

Pilosebaceous

anomalies

Matrix Degeneration

● Demodex folliculorum mites: Bacillus oleronius bacteria within

● Increased sulfated O-glycans in tear film

Many Theories of Ocular Rosacea

DEMODEX

1. Chronic Dry Eye

2. Corneal Vascularization

3. 2nd Bacterial Infections

4. Perforation

5. Increased graft failure after PK

Complications of Ocular Rosacea

Increased Graft Rejection in PK patients

Complications of Ocular Rosacea

Treatments

1. Lid hygiene: Warm Compresses Baby shampoo scrubs

2. Artificial tears, nonpreserved

3. Antibiotics po: doxycycline, tetracycline, clarithromycin,

metronidazole; Erythromycin for kids

4. Erythromycin ointment

5. Topical steroids

6. Restasis: Topical cyclosporine A b.i.d. x 3 mo

Usual Treatments of Ocular Rosacea

1. Intense Pulse Light Therapy (IPL)

3. LipiFlow

4. Intraductal MG Probing, Maskin

Newer Ocular Rosacea Treatments:

Doxycycline Risks:

Prevention

● Avoid foods, drinks, and situations that trigger outbreaks like sun

● Hat, sunglasses● increase Omega 3s intake

Usual Prevention:

Subtypes of ROSACEA

4. A Hidden Concern

1. If also had diabetes, tended to develop proliferative diabetic retinopathy

2. If they also had age related macular degeneration (ARMD), tended to develop wet ARMD

3. If they had a corneal transplant, they would tend to have a rejection more often.

Years of Observations of Ocular Rosacea

A Chance Encounter at Grand Rounds

Who is this man?

Nature. 2009 Jun 25;459(7250):1126-30. doi: 10.1038/nature08062.

Sandra Lora Cremers, MD, FACS Harvard Medical SchoolGrant: National Rosacea Society

Results: Patient 3, CD 31+

Results: Patient 1, CD31+

Results: Patient 1, VEGF+

1. Anti-Angiogenic at low doses

2. Anti-bacterial at higher doses

Doxycycline Magical Properties:

Central Theory of Rosacea by Sandra Lora Cremers, MD, FACS

Grants: Harvard's 50th Anniversary Scholars Grant; National Rosacea Society; Lion's Eye

Neuronal-Driven Angiogenesis NGF

PDGF

Central Theory of Rosacea by Sandra Lora Cremers, MD, FACS

Grant provided by National Rosacea Society

Neuronal-Driven Angiogenesis NGF

PDGF

Doxy

-

nitric oxide (NO) synthetase

mitochondrial genes, ER stress cascade, growth factors, interleukins, cell cycle regulators, integrins, and components of the extracellular matrix; TNF-alpha, IL-10 and IFNgamma

low dose 0.5mg/kg/d significantly reduces BV growth & migration

Low Oxygen state

Rosacea is a multifactorial, hyper-reactivity, vascular and neural based disease with a broad range of facial and ocular manifestations where normal vasodilation is greater and more persistent and involves an autoimmune component where microscopic amounts of extravasated plasma induce localized dermal and meibomian gland inflammation and where repeated external triggers lead to angiogenesis (the recruitment of new blood vessels), vasodilation, teleangiectasias, redness with eventual fibrosis and hypertrophic scarring of the dermis and meibomian glands.

Likely a central underlying factor in all subtypes of rosacea, particularly ocular rosacea, involves VEGF and similar angiogenic factors.

More Complete Definition of Rosacea

1. Is Severe Ocular Rosacea due to increased

angiogenesis activity at the lid margin?

2. Would they benefit from topical anti-

angiogenic medications?

Future Research For Ocular Rosacea

1. Do severe ocular rosacea patients have an

increased risk of systemic angiogenesis?

2. Do these patients need to be evaluated for

an increased risk of internal tumors or

metastasis if primary tumors present?

Future Research For Ocular Rosacea

1. Avoid inflammatory factors (triggers, sun, smoke)

2. Eat antioxidants, Omega 3s,

2. If must treat with doxycycline, use lowest dose Start with 20mg q day; 40-mg, controlled release formulation

of doxycycline monohydrate is an anti-inflammatory drug

3. General medical check ups

Recommendations for Ocular Rosacea Patients:

Thank you for your attention.

1. Rohrich RJ, Griffin JR, Adams WP., Jr Rhinophyma: Review and update. Plast Reconstr Surg.2002;110(3):860–869. quiz, 870. 2. Scheinfeld NS. Rosacea. Skinmed. 2006;5:191–194.

3. Glycomic analysis of tear and saliva in ocular rosacea patients: the search for a biomarker. Ocul Surf. 2012 Jul;10(3):184-92 , Vieira AC, An HJ, Ozcan S, Kim JH, Lebrilla CB, Mannis MJ.2. http://rosacea-support.org/ocular-rosacea-diagnostic-test-one-step-closer.html3. 4. Perry HD, Doshi-Carnevale S, Donnenfeld ED, et al. Efficacy of commercially available topical cyclosporine A 0.05%in the treatment of meibomian gland dysfunction. Cornea. 2006;25:171-1753. Stone, Curr Opin Ophthalmol, 2004http://www.rosacea-treatment.org/6. http://videos.med.wisc.edu/videos/375717. Doxycycline's Effect on Ocular Angiogenesis: an In Vivo Analysis. Ophthalmology 2010 Sept, 117(9): 1782-1791. Cox, C, et al. 8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3315879/9. Del Rosso JQ, Bikowski JB. Multicenter, doubleblind, randomized, placebo-controlled, parallelgroup trial results evaluating the effects of 40 mgdoxycycline monohydrate controlled-releasecapsules in the treatment of rosacea. Posterpresented at: 64 th American Academy ofDermatology Meeting ; March 3–7, 2006; San Francisco, Calif.

References:

9. Del Rosso JQ, Bikowski JB. Multicenter, doubleblind, randomized, placebo-controlled, parallelgroup trial results evaluating the effects of 40 mgdoxycycline monohydrate controlled-release capsules in the treatment of rosacea. Poster presented at: 64 th American Academy of Dermatology Meeting ; March 3–7, 2006; San Francisco, Calif.10.http://www.globalacademycme.com/fileadmin/pdf/supplement_pdf/fczjw6vm_sanews_supplement46.pdf

References continued: