Noninfectious KeratitisDr. Merce Morral

Institut Clínic d’Oftalmologia, Hospital Clinic i Provincial

Dr. Jose L. GuellInstituto de Microcirugia Ocular

Barcelona, Spain

Noninfectious Keratitis

I have no financial interest to disclose

Noninfectious keratitis• Recurrent Erosion Syndrome

• Filamentary Keratitis

• The Superficial Punctate Keratitis Of Thygeson

• Neurotrophic Keratitis

• Factitious Keratoconjunctivitis

1. Recurrent Erosion Syndromes• Repeated episodes of spontaneous breakdown of the corneal epithelium: Varied frequency and intensity - Evening or early morning

Trauma and/or Corneal Dystrophy (CD)

Abnormal Attachment Complexes

Recurrent Corneal Erosions

• Anterior basement (Cogan’s, map-dot-fingerprint) - 6-42%

• Other CD: lattice, Reis-Bucklers, macular granular, and Meesmann

• Diabetes mellitus

• Bullous keratopathy

MDFP1

RCE

1 Mencucci R. BJO. 2010;94(7):933-9

1. RES: Clinical Manifestations• Symptoms:

– Mild foreign body sensation (FBS) to abrupt “ripping or tearing” sensation followed by abrupt pain

– Epiphora, photophobia, lid swelling,…

• Signs: EXPLORE BOTH EYES

– Ragged, grayish-staining area of epithelium – negative staining

– Pressure on cornea: wrinkling of loosely adherent epithelium

– Browny edema: residual brown granularity of the stroma

– ABMD:

• Reduplication BM (maps)

• Cystic degeneration (microcysts)

1. RES: Medical Treatment

• Acute phase: topical antibiotics +/- patching

• Bandage contact lens, if abnormalities in lid anatomy – increased risk of bacterial keratitis

• Long-term nightly use of hyperosmotic lubricating ointments (6-12 months)

• Lubricants/autologous serum

• Treat dry eye and meibomian gland dysfunction

• Avoid topical steroids

1. RES: Surgical TreatmentProcedure Indications LimitationsDebridement •Localized loose sheet of floppy

epitheliumNo modifications in Bowman’s layer to enhance epithelial adhesion

Epithelial keratectomy

•Erosions in multiple areas •Moderate-severe ABMD•Large loose sheets of epithelium

Anterior stromal punctures/

YAG laser

•Localized erosions •Mild-moderate ABMD

AVOID if CENTRALScarring, risk of perforation

PTK •Erosions in multiple areas•Afecting CENTRAL cornea•Moderate-severe ABMD•Myopia

Hyperopic shift – minimized with current treatment profiles

2. Filamentary Keratitis

• Degenerated epithelial cells surrounding a mucous core firmly attached to the corneal surface at their base.

Pathophysiology:

– Abnormal Ocular Surface

– Degenerated epithelium

– Altered tear film chemistry (Mucous - viscosity)

Dr. JL Güell

2. FK: Clinical Manifestations• Symptoms:

– FBS, most prominent with blinking

– Epiphora, photophobia, blepharospasm

• Signs:

– Filaments: • Length: 0.5 mm to several mm• Firmly adherent to the cornea• RB +; fluorescein -

– Blinking may break the attachment – epithelial defect (fluo +) Dr. JL Güell

2. Filamentary Keratitis: Ethiology• Ophthalmic disorders:

– Keratoconjunctivitis sicca/Sjögren: most frequent– Neurotrophic keratopathy (herpetic, V paralysis)– Exposure keratopathy– Superior limbic keratoconjunctivitis– Prolonged patching– Ptosis– Anirida/Ocular albinism

• Ocular trauma/surgery: – Erosions– Contact lens overwear– Cataract Extraction– Penetrating keratoplasty

• Systemic disorders: sarcoid, diabetes mellitus, hereditary hemorrhagic telangiectasia, ectodermal dysplasia, psoriasis, atopic dermatitis, brain stem injury

Interpalpebral area

Superior

Graft near sutures or G-H interface

2. FK: Treatment• Identify and treat (if possible) underlying cause

• Mechanical debridement of the filaments (temporary) – try not to disrupt underlying epithelium

• Treat KC Sicca:– Preservative-free topical tear substitutes– Punctal plugs– Topical steroids– Botulinum toxin, palpebral surgery – decrease exposure

• Hyperosmotic lubricating solution and ointment

• 10% N-acetylcysteine – mucolytic agent

• Soft contact lens

• 0.1% or 1% diclophenac sodium

• Unproved: eledoisin, beta irradiation, topical heparin, topical dextran, systemic mucolytics, topical humanEGF,…

3. The Superficial Punctate Keratitis of Thygeson

• 1950 – Thygeson1

• Coarse punctate epithelial keratitis with little or no conjunctival hyperemia

• Unknown cause or associated disease:

– Viral origin currently not believed

– Immune process? – association with HLA-DW3 and HLA-DR3

• Second-third decades (any age), no sex preference

1. Thygeson P. Superficial punctate keratitis. JAMA 1950;144:1544-1549

• Diagnostic features1:

– Chronic, bilateral, punctate epithelial keratitis

– Long duration – remissions (months to years) and exacerbations (weeks up to 8 months)

– Healing without scarring

– Lack of response to topical antibiotics or epithelial debridement

– Striking symptomatic response to topical corticosteroids

• Spontaneous remissions and exacerbations of FBS, tearing, burning, photophobia, occasional blurring of vision

3. The Superficial Punctate Keratitis of Thygeson

1. Thygeson P. Superficial punctate keratitis. JAMA 1950;144:1544-1549

• 15-20 fine granular, white to gray dot-like epithelial opacities

• Stellate appearance (dxd herpes virus)

• Little epithelial edema, no cellular infiltration

• Evanescent, predominantly in the central cornea

• Exacerbations: raised center breaks through the epithelial surface, fluorescein and rose bengal staining

• Remissions: flat and do not stain

3. Thygeson

Dr. JL Güell

3. Thygeson: Treatment• Low-dose topical corticosteroids – some believe steroids prolong the

course of the disease1

• Relive symptoms with therapeutic CL

• Cyclosporin A 2%, FK506

• Idoxuridine contraindicated as may produce subepithelial scarring

• Epithelial debridement or chemical cauterization useless and may produce scarring or ulceration.

1. Tabbara KF et al. Thygeson’s superficial punctate keratitis. Ophthalmology 1981;88:75-77

4. Neurotrophic keratitis (NK)• Impaired healing in absence of corneal sensitivity (denervation and

corneal limbal stem cell deficiency)1-3: > anesthesia > neurotrophic changes Melting – corneal perforation

1. Mackie IA. Role of the corneal nerves in destructive disease of the cornea. Trans Ophthalmol Soc UK 1978;93:3732. Cavanagh HD, et al. The molecular basis of neurotrophic Keratitis. Act Ophthalmol Suppl 1989;192:1153. Puangsricharem V. Cytologic evidence of corneal diseases with limbal stem cells deficiency. Ophthalmology 1995;102:1476-85

Pathophysiology:

– Corneal hypo/anaesthesia

– Decreased reflex tearing and blinking rates

– Poor corneal lubrication and epithelial healing

• Most frequent: HSV/HZV – (21% corneal hyposthesia)

• 2ond: V nerve palsy secondary to surgical procedure (V neuralgia)

• Most severe: ressection of acoustic neurinoma - combination of V + VII

• Diabetes mellitus – peripheral neuropathy

• Topical medications: timolol, diclofenac, anesthetic

• Systemic medications: Epithelial growth factors inhibitors

4. NK

V + VII palsy

Herpes simplex

4. NK: Clinical Evaluation• Thorough medical and surgical history to determine the cause for corneal

hypesthesia:– Explore other cranial nerves --- neurologist and cranial imaging studies

Evaluation Pathology

III, IV, VI Ocular motility Aneurism Cavernous sinus pathology

VII, VIII Facial motility and hearing Acoustic neurinoma

II Aferent pupillary defect Lesion in intraconal orbit

Sympathetic inervation iris

Anisocoria (Eferent pupillary defect) Lesion in intraconal orbit

• Eyelid function – PROGNOSIS

• Degree and pattern of corneal hypesthesia – SEVERITY (HZV; patchy)

4. NK: Clinical Evaluation• Ocular surface examination:

– Qualitative and quantitative tear function: Schirmmer’s, TBUT

– Fluorescein and Rose Bengal staining

– Presence of stromal infiltration, thinning, scarring,..

• Complete ophthalmological examination: iris atrophy (herpes), optic nerve pallor or swelling (orbit lesion),..

Mackie I.A.: Role of the corneal nerves in destructive disease of the cornea. Trans Ophthalmol Soc UK 1978;98:343-347.

Mackie IA – 3 Clinical Stages

4. Neurotrophic Keratitis: Clinical Stages• Stage 1

– Rose bengal staining of the palpebral conjunctiva– Decreased tear break-up time– Increased viscosity of tear mucus– Punctate epithelial staining with fluorescein– Scattered small facets of dried epithelium (Gaule spots)

4. Neurotrophic Keratitis: Clinical Stages• Stage 2:– Acute loss of epithelium, usually under the upper lid– Surrounding rim of loose epithelium– Stromal edema– Aqueous cell and flare– Edges of the defect become smooth and rolled with time

4. Neurotrophic Keratitis: Clinical Stages• Stage 2:– Acute loss of epithelium, usually under the upper lid– Surrounding rim of loose epithelium– Stromal edema– Aqueous cell and flare– Edges of the defect become smooth and rolled with time

4. Neurotrophic keratitis: Clinical Stages• Stage 3:– Stromal lysis – corneal perforation: inflammation, secondary infection, and

imprudent use of topical steroids.

Herpes simplex EGF inhibitors

4. NK: Treatment• Treat eyelid disfunction

• Stage 1:– Preservative-free topical lubrication– Therapeutic CL (increases the risk for infectious keratitis)– Punctal silicone plugs – Doxycycline: improves tear quality (MGD) and prevents stromal lysis.

• If severe loss of corneal sensation: lateral tarsorrhaphy, botulinum A toxin injection of the levator – decrease exposition and prevent evolution to stage 2 and 3

• If severe dry eye: CsA, Autologous serum (20%-50%), autologous platelet-rich plasma drops

• In presence of inflammation: Avoid NSAIDS – cause corneal hypoaesthesia; Cautious use of steroids: preservative-free and add topical antibiotic

• Pharmacological adjuncts (research): EGF, topical aldose reductase inhibitors (DM), NGF, substance P, thymosin beta4

4. NK: Treatment of Stage 3• Amniotic Membrane Transplantation (AMT):

– Graft in trophic corneal ulceration1,2

– Patch to cover epithelial defects3

• Perforation < 2mm: cyanoacrylate glue + bandage CL

• Perforation > 2mm: Lamellar or penetrating keratoplasty +/- AMT– Increased risk for rejection due to NV, poor wound healing, poor reepithelization of the graft due to

hypoaesthesia, …

• Conjunctival flaps:– Poor cosmetic and visual results– Impairs subsequent PKP

1. Gris O, et al. Amniotic membrane transplantation for ocular surface pathology: long-term results. Transplantation Proceedings 2003;35:2031-5

2. Gris O, et al. Histological findings after amniotic membrane graft in the human cornea. Ophthalmoogy 2002;109:508-123. Gris O, et al. Amniotic membrane implantation as a therapeutic contact lens for the treatment of epihelial disorders. Cornea

2002;21:22-7

EGF inhibitors: Cyanoacrylate glue and BCL

HSV: AM graft

Perforation of a herpetic peripheral corneal ulcerPenetrating keratoplasty + lensectomy + anterior vitrectomy + subconjunctival Avastin®

BSCVA: LP

BSCVA: 20/100 BSCVA: 20/50

Dr. JL Güell

5. Factitious Keratoconjunctivitis• Factitious disorders: Symptoms or physical findings intentionally produced by

the patient to assume the sick role in abscence of external incentive (Malingering) – Anaesthetic abuse

– Age: 2nd or 3rd decade– Employed in the medical field– Deny any history of trauma– Multiple recurrent episodes of poorly explained disease– Failure to respond to appropriate therapy– Improve dramatically when placed on 24-hour watch– Display less concern for the presenting problem than

appropriate: “serene indiference”

Take-home messages• Always rule out infectious origin

• RES: trauma or corneal epithelial dystrophy – PTK if medical treatment not effective

• FK: dry eye and ocular surface abnormalities – lubrication, topical steroids, hyperosmotics

• Thygeson: dxd viral keratitis – chronic course (remissions-exacerbations) – topical steroids

• Neurotrophic keratitis: IDENTIFY and TREAT the cause that leads to corneal hypesthesia – herpes virus and V palsy – aggressive and prompt treatment