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Optic Nerve Sarcoidosis

(Presenting as Unilateral Optic Nerve Head Mass)

Dr Jakub Khzouz

Fellow Ophthalmic Pathology (ECF)

Liverpool Ocular Oncology Group

History

• A 61 year old gentleman with history of vision loss in the right eye since one year.

• He complains of eye pain.

Examination

Right eye Left eye

Visual acuity No perception 6/6

IOP 41mm Hg. 19mm Hg.

Fundoscopy (Right eye)

Examination

• There is a non pigmented sub retinal lesion covering the optic nerve head.

• All retinal blood vessels seems to be occluded.

• There is neovascular rubeosis of the iris.

• No significant lesion in the left eye.

Impression

• Based on the clinical examination alone no diagnosis was established.

• DDx (indeterminate optic nerve head lesion):

• Vitreoretinal lymphoma.

• Melanoma.

• Intra-ocular sarcoid.

• Previous medical history included Hodgkin lymphoma 3 years ago treated by chemo and radiotherapy on follow up (PET scan relapse stage 3).

• Mediastinal Sarcoidosis.

Treatment

• Based on no perception of light and neovascular glaucoma with a painful and blind eye; right eye enucleation with implant was recommended .

Enucleation

• Fresh intact right globe

• 24.5mm(Ax)x23.3mm(Hz)x23.5mm(Vr)

• Cornea: 12mm(Hz)x11.5mm(Vr)

• Optic nerve: 6mm(length)x4mm(diameter).

• Trans-illumination: No shadow.

• On opening at disc there is a white yellow mass measuring 3.3x4mm.

CD68

CD68

CD68

CD68

Special stains.

• Special stains for Acid fast bacilli and Fungi are negative.

The Eye as a Common Site for the Early Clinical Manifestation of Sarcoidosis

• Sarcoidosis can involve almost any structure within or around the eye.

• Ocular involvement ranges from 13% to 79% of patients with systemic sarcoidosis.

• The first recognized clinical manifestation of sarcoidosis often is eye disease (20%-30%).

• A broad range of eye involvement has been noted previously, the most frequent findings being anterior uveitis (35%), posterior uveitis (25%), lacrimal gland involvement (25%), sicca syndrome (15%), conjunctival involvement (17%) and optic disc involvement (3%).

• Granulomatous lesions in the eyes represented the first sign of sarcoidosis in 2% of the patients, and 3% of the patients developed sarcoidosis in the subsequent 4 years.

• Females are more likely to develop ocular involvement (2:1).

• Two peaks of incidence are 20-30 years and 50-60 years.

Heiligenhaus A, Wefelmeyer D, Wefelmeyer E, Rosel M, Schrenk M. The eye as a common site for the early clinical manifestation of sarcoidosis. Ophthalmic Res. 2011; 46(1):9–12.

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Organ manifestations and clinical syndromes typical of sarcoidosis detected at the first visit in the clinic (1,800 patient)

Thorax Eye Erythema Nodosum Lofgren SyndromeSkin Liver LN JointsParotid Nervous System Heart MusculoskeletalKidney Thyroid

Initial clinical organ manifestations and syndromes typical of sarcoidosis in 1800 patient.

Organ/Syndrome

Eye Joints Skin

Fever,malaise,weight loss Erythema N Parotid enlargment

Nervous system LNs Others (GI,thyroid, URT, Muscle,Heart…)

Ocular manifestation at first visit in 662 patientsMutton-fat Keratic precipitate 25%

Iris granulomas 29%

Trabecular meshwork granulomas/peripheral anterior synechiae 9%

Snow balls/strings of pearls in the peripheral vitreous 53%

Multiple peripheral chorioretinal scars or active lesions 28%

Nodular or segmental periphlebitis 14.5%

Retinal microaneurysms 12%

Optic disc granulomas 2%

Solitary choroidal granulomas 7%

Bilateral disease 88%

Eye manifestations in 381 patients in whom these were the initial clinical signs of sarcoidosis

Eye disease %

Anterior uveitis 76.4

Intermediate uveitis 17.3

Posterior uveitis 4.7

Optic nerve involvement 0.8

Lacrimal gland swelling 0.5

Conjunctival involvement 0.3

Clinical manifestations of ocular sarcoidosisOcular structures Ophthalmic manifestations

Eyelids Eyelid granuloma, madarosis (loss of eyelashes), poliosis (whitening of lashes), entropion, trichiasis, Lagophthalmos (if associated with facial palsy)

Conjunctiva Conjunctival nodules or granuloma, conjunctivitis, symblepharon, conjunctival cicatrization

Episclera/sclera Episcleritis, scleritis

Cornea Peripheral ulcerative keratitis, interstitial keratitis, exposure keratopathy, band keratopathy

Trabecular meshwork and anterior chamber angle Trabecular granuloma, peripheral anterior synechiae, ocular hypertension, glaucoma

Iris Anterior uveitis (iritis), iris nodules/granuloma, posterior synechiae, pupillary abnormalities

Lens Cataract

Pars plana/vitreous Intermediate uveitis

Pasadhika S, Rosenbaum JT. Ocular Sarcoidosis. Clinics in Chest Medicine. 2015 Dec;36(4):669-83.

Clinical manifestations of ocular sarcoidosis

Ocular structures Ophthalmic manifestations

Retina Retinitis, retinal vasculitis, macular edema

Choroid Choroiditis, granuloma

Optic nerve Papillitis, papilledema (increased intracranial pressure due to neurosarcoid), granuloma, optic neuropathy (compressive or infiltrative), optic atrophy

Lens Cataract

Lacrimal gland Granuloma, dacryoadenitis, keratoconjunctivitis sicca (dry eye)

Nasolacrimal drainage system Nasolacrimal duct obstruction

Extraocular muscles and other orbital tissues Granuloma, strabismus, proptosis, optic nerve compression

Intracranial lesions involving visual pathway Decreased vision, visual field defects, abnormal pupillary response, abnormal eye movement

Pasadhika S, Rosenbaum JT. Ocular Sarcoidosis. Clinics in Chest Medicine. 2015 Dec;36(4):669-83.

Optic nerve involvement due to sarcoidosis

1- Optic disc oedema secondary to posterior uveitis.

2- Optic disc oedema secondary to raised intracranial pressure.

3- Optic neuritis (retro bulbar neuritis).

4- Optic atrophy secondary to compression or infiltration from a primary central nervous system lesion.

5- Primary granuloma of the optic nerve head.

Ingestad R, Stigmar G. Sarcoidosis with ocular and hypothalamic pituitary manifestations. Acta Ophthalmologica 1971;49:1–10.

Optic nerve head granuloma reports

• 34 cases (17 males+17 females)

• 10 black/African American, 3 white/caucasian, and 2 south Asian.

• Mean age 34, range 11-59.

• 27 unilateral / 7 bilateral at presentation.

• 23/34 was first presentation.

• 37/41 eyes had additional ocular features of sarcoidosis.

• 23/29 treated with steroids; 3 of them needed MTX.

• Visual acuity: 10/27 recovering to 20/20 or better, but 9/27 were 20/200 or worse at last follow-up.

S. J. Hickmana, F. Quhillb, and I. M. Pepperb. The Evolution of an Optic Nerve Head Granuloma Due to Sarcoidosis. NEURO-OPHTHALMOLOGY 2016, VOL. 40, NO. 2, 59–68 .

Histologic findings (case 1)

• Enucleation due to painful anterior uveitis and secondary glaucoma.

• Showed non-caseating granulomatous inflammation protruding forward through the scleral canal with an overlying retinal detachment.

Histologic findings (case 2)

• Enucleation.

• The optic nerve head anterior to the lamina cribrosa was oedematous with a large nodule of epithelioid cells and lymphocytes adjacent to the outer nuclear layer of the retina.

• A further nodule was present in the centre of the optic cup.

• Near the optic nerve head the retinal vessels were markedly distended with numerous haemorrhages.

Histologic findings (case 3)

• Autopsy.

• The optic nerve head and surrounding retina were heavily infiltrated by a non-necrotising granulomatous reaction extending from the inner retinal layers and the surface of the optic disc in to the vitreous.

• This was associated with lymphocytic and neutrophilic perivascular infiltration as well as non-caseating epithelioid cell nodules and giant cells.

• There was also prominent folding of the peripapillary retina.

Neurosarcoidosis

• 5%–15% of cases • Meningitis, hydrocephalus, parenchymal involvement (particularly

hypothalamus or pituitary), encephalopathy, seizures, dural venous thrombosis, vasculitis, cranial neuropathy and peripheral neuropathy have all been reported in neurosarcoidosis.

• 82–100% of patients with neurosarcoidosis will have MRI that shows pathologic enhancement or parenchymal lesions.

• Neurosarcoidosis can be the presenting or only clinical manifestation of sarcoidosis and it was noted that 80% of patients (#67) presented without a prior sarcoidosis diagnosis.

• The predominant neuro-ophthalmic manifestation was optic neuropathy (optic nerve or chiasm enhancement on MRI) (70%) .

Koczman JJ, Rouleau J, Gaunt Met al. Neuro-ophthalmic Sarcoidosis: The University of Iowa Experience. Seminars In Ophthalmology 2008 May-Jun;23(3):157-68.

Glaucoma and Cataract

• Glaucoma may result from trabecular meshwork dysfunction due to oedema or obstruction from inflammatory cells.

• Severe or chronic anterior chamber inflammation may cause angle closure glaucoma secondary to peripheral anterior synechiaeformation.

• Cataract formation is also common in patients with sarcoid uveitis and leads to visual loss.

• Elevated IOP can also be related to orbital mass effects or side effects from corticosteroid therapy (which can also cause cataracts).

International Criteria for the Diagnosis of Ocular SarcoidosisOcular signs suggestive for ocular sarcoidosis

1. Mutton-flat keratic precipitates and/or iris nodules

2. Trabecular meshwork nodules and/or tent-shaped peripheral anterior synechiae

3. Snowballs or string of pearls in the vitreous

4. Active or inactive multiple chorioretinal peripheral lesions

5. Nodular and/or segmental periphlebitis and/or macroaneurysms in an inflamed eye

6. Optic disc nodule(s)/granuloma(s) and/or solitary choroidal nodule

7. Bilateral involvement

Pasadhika S, Rosenbaum JT. Ocular Sarcoidosis. Clinics in Chest Medicine. 2015 Dec;36(4):669-83.

Laboratory investigations in patients suspected for ocular sarcoidosis

1. Negative tuberculin test in a BCG vaccinated patient or with previous positive PPD (or Mantoux) skin test

2. Elevated serum level of angiotensin converting enzyme (ACE) and/or lysozyme

3. Chest x-ray for bilateral symmetric hilar adenopathy

4. Abnormal liver enzyme tests (any 2 of alkaline phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) or gamma-glutamyl transferase (GGT))

5. Chest computerized tomography in patients with negative chest x-ray

Pasadhika S, Rosenbaum JT. Ocular Sarcoidosis. Clinics in Chest Medicine. 2015 Dec;36(4):669-83.

Diagnostic criteria and terminologies for ocular sarcoidosis

Definite ocular sarcoidosis Biopsy-proven with a compatible uveitis

Presumed ocular sarcoidosis Biopsy not performed; bilateral hilar adenopathy (BHL) with compatible uveitis

Probable ocular sarcoidosis Biopsy not performed and no BHL detected; presence of 3 suggestive ocular signs and 2 positive above laboratory tests

Possible ocular sarcoidosis Biopsy negative; presence of 4 suggestive ocular signs and 2 positive above laboratory tests

Pasadhika S, Rosenbaum JT. Ocular Sarcoidosis. Clinics in Chest Medicine. 2015 Dec;36(4):669-83.

Thank You