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Uwe Pleyer

Scleritis

Sclera “on Fire”…

Febr. 29th, 2020

…the human eye with its prominent sclera serves critical

communicative functions during human social interactions…

Sarah Jessen and Tobias Grossmann Proc Natl Acad Sci USA 111:16208-13 (2014)

Scleritis is an uncommon disease

Incidence: approx. 3.4/100,000/year

Annual prevalence: 5.2/100,000 persons 4%

McCartney 1988

Scleritis: Epidemiology

Homayounfar G. et al. Investigative Ophthalmology & Visual Science June 2013, Vol.54, 889.

Anatomie I: Skleritis -Epidemiology (Epi-) Scleritis 9:1

Foster, Sainz de la Maza „The Sclera“, Springer Berlin, 2008

Scleritis

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Main complains…?

Symptoms/Signs

Pain 90%

Impaired V/A 80%

Inflammation 75%

Lid edema 10%

4%McCartney 1988

Main complains: Scleritis

Pohlmann D, Pleyer U. Scleritis - Progress in Diagnosis and Therapy. Klin Monbl Augenheilkd. 235:603-610 (2018)

Main complains: Episcleritis

Symptoms/Signs

Pain 10%

Impaired V/A 10%

Redness 75%

Lid edema absent

4%

Pohlmann D, Pleyer U. Scleritis - Progress in Diagnosis and Therapy. Klin Monbl Augenheilkd. 235:603-610 (2018)

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History

Typical: presentation as "chronic inflammation,

that does not respond to antibiotics“…

Bisphosphonate treatment?

Organ-specific history: key symptoms

Infarcts? (Heart, mesenteric vessels, brain)

Painful rashes? (Vasculitis)

„Bloody cold“? (Polyangiitis – Wegener)

Paresis / sensory disturbance? (Neuropathy)

Angina abdominalis? (Mesenteric)

Hemoptysis? (alveolar capillariitis)

Headache? (CNS)

„Rheumatic“ complaints?

Pohlmann D, Pleyer U. Scleritis - Progress in Diagnosis and Therapy. Klin Monbl Augenheilkd. 235:603-610 (2018)

Patient history

Inflammatory 40%Joint diseases andrheumatic disorders

Rheumatoid arthritisChronic enteropathiesSystemic lupus erythematosussarcoidosisRecurrent polychondritisAnkylosing spondylitisReiter syndromePsoriatic arthritis

Vasculitis 10%

Granulomatosis u. polyangitisPeriarteritis nodosaM. BehçetGiant cell arteritisCogan syndromeChurg-Strauss syndrome

Other 2%

Atopyrosaceagouttrauma"Masquerade"

Infections 7%

VZV, HSVTuberculosis, syphilis, borreliaAcanthamoeba, Toxocariasismycoses

Pohlmann D, Pleyer U. Scleritis - Progress in Diagnosis and Therapy. Klin Monbl Augenheilkd. 235:603-610 (2018)

Lane J et al. Clinical Features of Scleritis Across the Asia-Pacific Region. Ocul Immunol Inflamm. 28:1-7 (2018)

Scleritis & EpiscleritisAssociated Disorders

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Foster Watson Berlin

n=128 n=205 n=267

Episcleritis 31% 32% 14%

Scleritis 57% 57% 41%

Diffuse 45% 25% 39%

Nodular 44% 45% 38%

Necrotizing 94% 95% 82%

Posterior 45% 40% 28%

Episcleritis and scleritisAssociated disorders

Diagnosis of systemic disorders

40% before scleritis - 25% at initial visit - 35% during follow - up Feist E, Pleyer U. Diseases of the outer eye in rheumatoid arthritis. Z Rheumatol. (2010)

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Morphology

Phenylephrine test

for episcleritis

From: Foster, Sainz de la Maza „The Sclera“

Which structure is affected?

Foster, Sainz de la Maza „The Sclera“, Springer Berlin, 2008

Which structure is affected?

Diffuse (38%) Nodular (39%)

Which structure is affected?Anterior Scleritis: non-necrotizing (n=267)

Pohlmann D, Pleyer U. Scleritis - Progress in Diagnosis and Therapy. Klin Monbl Augenheilkd. 235:603-610 (2018)

Which structure is affected?Anterior necrotizing Scleritis (23%)

Prognostic signs

Vascular occlusions

and anastomoses to uvea

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Investigations

Laboratory parameters

Pohlmann D, Pleyer U. Scleritis - Progress in Diagnosis and Therapy. Klin Monbl Augenheilkd. 235:603-610 (2018)

Diogo et al. American Journal of Neuroradiology 37: 2334-2339 (2016)

Weiss K, Rieger R, Keitzer R, Pleyer U.

Infliximab treatment of posterior scleritis.

Graefes Arch Clin Exp Ophthalmol. 2007; 245:1735-7.

Imaging in scleritis

P Watson and A Romano The impact of new methods of investigation and treatment on the

understanding of the pathology of scleral inflammation Eye (2014) 28, 915–930

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Interdisciplinary

Approach

Radiology Typical findings in inflammatory systemic diseases

X-ray thorax Suspicious for sarcoidosis, TBc, Polyangitis

CT or MRI skull (including paranasal sinuses)

e.g. shadow of the paranasal sinuses, infiltrations, GPA (Wegener)

Granulomatosis with polyangiitis (GPA)

Tuberculosis

Interdisciplinary approach

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Establish „Diagnosis“

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Granulomatosis with Polyangiitis –

Rheumatoid arthritis

Rheumatoid arthritis Psoriasis

TNF-blocker IL-17 -blocker

Dependent on systemic DX

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Treatment plan

Treatment goals

R elief of symptoms

R educe inflammation and recurrences

R estore morphological and functional changes

Patients with diffuse / nodular ScleritisModerate Pain

Pain relief: After 1-2 days

Often effective: (Charité: 78/137 patients)

Therapy duration: In isolated episode: 2-3 weeks

With frequent recurrences: approx. 2-3 months

NSAIDs:

Agent: Dosage:

Diclofenac 1-3 x 25-50mg

Ketoprofene (Orudis®) 1-2 x 50-100mg

Ibuprofene 1-2 x 200-400mgNaproxen (Proxen®) 1-2 x 250-500mg

Indometacine 1-2x 25-50mg

Meloxicame (Mobec®) 1-2x 7,5mg

Selective Cox-2-inhibitors*

Agent: Dosis:

Celebrex® Celecoxib 2x100mg

Arcoxia® Etoricoxib 90/120mg

* https://www.aao.org/focalpoints

Topical

- Steroids; NSAID´s

Systemic

- (NSAIDs)

- Steroids

- Immunosuppressants

- Biologicals

Stem MS et al. Ocular Pharmacology for Scleritis: Review of Treatment and a Practical Perspective.J Ocul Pharmacol Ther. 2017 May;33(4):240-246.

Treatment goal: InflammationIs there a role for local injection(s)?

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0

100

200

300

400

500

600

700

präoperativ 1. Monat 3. Monat 6. Monat

00,5

11,5

22,5

33,5

präoperativ 1. Monat 3. Monat 6. Monat

Patient 1

Patient 2

Patient 3

Patient 4

Patient 5

Reduction of CRT (µm) Reduction of scleritis

3+654 µm 297 µm 0+

Intravitreal Dexamethasone (Ozurdex)

in Scleritis + CME

Pohlmann D, Winterhalter S, Pleyer U. Intravitreal Dexamethasone for CMO with Sclerouveitis. Ocul Immunol Inflamm. 20:1-6, 2016

Indications

– In severe systemic disorders (with high lethality)

– No response to corticosteroids

– High steroid maintance dosage (7.5 mg/d Prednisolone)

– Adverse effects to corticosteroids (systemic or ocular)

– To reduce corticosteroid dosage

Immunosuppression always with adequate monitoring

ScleritisImmunosuppression

Classical Immunsuppressants (DMARs)MethotrexateAzathioprineCyclosporine AMycophenolacidCyclophosphamide

Biologicals (bDMARs)

TNF-alpha inhibitors (Infliximab, Adalimumab, Golimumab)

Anti-CD-20 (Rituximab)

Anti-IL-6R (Tocilizumab)

ScleritisWhich immunosuppressive agent? (Level EbM 2C)

Delayed onset of effect: up to 3 months !

(initiate treatment with corticosteroids)

Levy-Clarke G et al. Expert panel recommendations for the use of anti-tumor necrosis factor biologic agents

in patients with ocular inflammatory disorders. Ophthalmology. (2014) https://www.aao.org/focalpoints

Classical Immunsuppressants (DMARs)MethotrexateAzathioprineCyclosporine AMycophenolacid

Cyclophosphamide

Biologicals (bDMARs)

TNF-alpha inhibitors (Infliximab, Adamilumab, Etanercept)Anti-CD-20 (Rituximab)Anti-IL-6R (Tocilizumab)

ScleritisWhich Immunosuppressive agent?

Delayed onset of effect: up to 3 months !

(initiate treatment with corticosteroids)

Levy-Clarke G et al. Expert panel recommendations for the use of anti-tumor necrosis factor biologic agents in patients with ocular inflammatory disorders

Ophthalmology. (2014)

Stone JH et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med 2010; 363:221

Cyclophosphamide

Classical Immunsuppressants (DMARs)MethotrexateAzathioprineCyclosporine AMycophenolacidCyclophosphamide

Biologicals (bDMARs)

TNF-alpha inhibitors (Infliximab, Adalimumab, Etanercept)

Anti-CD-20 (Rituximab*) GPAAnti-IL-6R (Tocilizumab)

ScleritisWhich Immunosuppressive agent?

Delayed onset of effect: up to 3 months !

(initiate treatment with corticosteroids)

Stone JH et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med 2010; 363:221

Specks U et al. Efficacy of remission-induction regimens for ANCA-associated vasculitis. N Engl J Med 2013; 369:417

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Infliximab in Scleritis TNF inhibitors in scleritis

Rituximab in Scleritis

Figure 1. Time to remission (days) after first rituximab course

in patients with ocular GPA with scleritis and orbital disease.

— Scleritis; - - orbital disease.

Rituximab in Scleritis

Predictor of recurrences

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Treatment control

Ophthalmology, Volume 118, Issue 4, 2011, 768–771

Severity of scleritis?

P Watson and A Romano Eye (2014) 28, 915–930

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71-y.o. patient with necrotizing scleritis and rheumatoid arthritis

under steroid/MTX therapy worsening condition

Necrotising scleritis

with micro abscesses

VZV Antigen pos.

Therapy

Acyclovir 5x800mg i.v.

topical Cyclosporin A 2%

Scleritis: are they all the same…?

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Care for secondary findings

ScleritisMultiple ocular complications (n=267)

• Uveitis (n=48)

• Cataract (n=24) (52%)

• Sec. Glaucoma (n=33)

• Cornea

peripheral infiltrates

interstitial keratitis (IK)

peripheral ulcerative keratitis (PUK)

• Papilla edema

• Choroidal folds

• Macula edema

• Retina detachment

• Myositis

• Orbital inflammation

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Long term monitoring

Steroids: adverse effects

Risks of biologicals Side effects & paradoxial reactions

Havmose M, Thomsen SF. Int J Dermatol. 2017; 56: 1087-1102

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Summary: Scleritis

Often a serious disorder

Individual work-up

- Clinical findings

- Systemic disorder?

- Severity (grading)

Increasing spectrum of

therapeutic options

Interdisciplinary cooperation!

Treatment may have impact not only on the eye

but also to the life of the patient

Tak for din opmærksomhed

uwe.pleyer@charite.de