This document discusses different types of noninfectious keratitis, including recurrent erosion syndrome, filamentary keratitis, Thygeson's superficial punctate keratitis, and neurotrophic keratitis. Recurrent erosion syndrome involves repeated breakdown of the corneal epithelium and is associated with trauma, corneal dystrophy, or abnormal attachment complexes. Filamentary keratitis features filaments of degenerated epithelial cells firmly attached to the cornea. Thygeson's keratitis presents as chronic, bilateral punctate epithelial keratitis of unknown cause. Neurotrophic keratitis results from impaired corneal healing due to denervation and involves decreased tearing and blinking. Treatment focuses on managing underlying causes and symptoms for each condition.

1. Noninfectious Keratitis
Dr. Merce Morral
Institut Clínic d’Oftalmologia, Hospital Clinic i Provincial
Dr. Jose L. Guell
Instituto de Microcirugia Ocular
Barcelona, Spain

2. Noninfectious Keratitis
I have no financial interest to disclose

3. Noninfectious keratitis
• Recurrent Erosion Syndrome
• Filamentary Keratitis
• The Superficial Punctate Keratitis Of Thygeson
• Neurotrophic Keratitis
• Factitious Keratoconjunctivitis

4. • Repeated episodes of spontaneous breakdown of the corneal epithelium:
1. Recurrent Erosion Syndromes
Varied frequency and intensity - Evening or early morning
Trauma and/or Corneal Dystrophy (CD) •Anterior basement (Cogan’s, map-
dot-fingerprint) - 6-42%
Abnormal Attachment Complexes •Other CD: lattice, Reis-Bucklers,
macular granular, and Meesmann
•Diabetes mellitus
Recurrent Corneal Erosions
•Bullous keratopathy
RCE
MDFP1
1 Mencucci R. BJO. 2010;94(7):933-9

5. 1. RES: Clinical Manifestations
• Symptoms:
– Mild foreign body sensation (FBS) to abrupt “ripping or tearing”
sensation followed by abrupt pain
– Epiphora, photophobia, lid swelling,…

6. • 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)

7. 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

8. Procedure Indications
1. RES: Surgical Treatment Limitations
Debridement •Localized loose sheet of floppy No modifications in
epithelium Bowman’s layer to
enhance epithelial
adhesion
Epithelial •Erosions in multiple areas
keratectomy •Moderate-severe ABMD
•Large loose sheets of epithelium
Anterior stromal •Localized erosions AVOID if CENTRAL
punctures/ •Mild-moderate ABMD Scarring, risk of
YAG laser perforation
PTK •Erosions in multiple areas Hyperopic shift –
•Afecting CENTRAL cornea minimized with current
•Moderate-severe ABMD treatment profiles
•Myopia

9. 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

10. 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

11. 2. Filamentary Keratitis: Ethiology
• Ophthalmic disorders:
– Keratoconjunctivitis sicca/Sjögren: most frequent
Interpalpebral area
– Neurotrophic keratopathy (herpetic, V paralysis)
– Exposure keratopathy
– Superior limbic keratoconjunctivitis
– Prolonged patching Superior
– Ptosis
– Anirida/Ocular albinism
• Ocular trauma/surgery:
– Erosions
– Contact lens overwear
– Cataract Extraction
– Penetrating keratoplasty Graft near sutures or G-H interface
• Systemic disorders: sarcoid, diabetes mellitus, hereditary hemorrhagic telangiectasia,
ectodermal dysplasia, psoriasis, atopic dermatitis, brain stem injury

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

13. 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

14. 3. The Superficial Punctate Keratitis of Thygeson
• 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
1. Thygeson P. Superficial punctate keratitis. JAMA 1950;144:1544-1549

15. 3. Thygeson
• 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
Dr. JL Güell

16. 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

17. 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
Pathophysiology:
– Corneal hypo/anaesthesia
– Decreased reflex tearing and
blinking rates
– Poor corneal lubrication and
epithelial healing
1. Mackie IA. Role of the corneal nerves in destructive disease of the cornea. Trans Ophthalmol Soc UK 1978;93:373
2. Cavanagh HD, et al. The molecular basis of neurotrophic Keratitis. Act Ophthalmol Suppl 1989;192:115
3. Puangsricharem V. Cytologic evidence of corneal diseases with limbal stem cells deficiency. Ophthalmology 1995;102:1476-85

18. 4. NK
• 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

19. V + VII palsy
Herpes simplex

20. 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 Anisocoria (Eferent pupillary defect) Lesion in intraconal orbit
inervation iris
• Eyelid function – PROGNOSIS
• Degree and pattern of corneal hypesthesia – SEVERITY (HZV; patchy)

21. 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 IA – 3 Clinical Stages
Mackie I.A.: Role of the corneal nerves in destructive disease of the cornea.
Trans Ophthalmol Soc UK 1978;98:343-347.

22. 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)

23. • Stage 2:
4. Neurotrophic Keratitis: Clinical Stages
– 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

24. • Stage 2:
4. Neurotrophic Keratitis: Clinical Stages
– 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

25. 4. Neurotrophic keratitis: Clinical Stages
• Stage 3:
– Stromal lysis – corneal perforation: inflammation, secondary infection, and
imprudent use of topical steroids.
Herpes simplex EGF inhibitors

26. 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

27. 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;109:508-12
3. Gris O, et al. Amniotic membrane implantation as a therapeutic contact lens for the treatment of epihelial disorders. Cornea
2002;21:22-7

28. EGF inhibitors: Cyanoacrylate glue and BCL
HSV: AM graft

29. Perforation of a herpetic peripheral corneal ulcer
Penetrating keratoplasty + lensectomy + anterior vitrectomy + subconjunctival Avastin®
BSCVA: LP
BSCVA: 20/100 BSCVA: 20/50
Dr. JL Güell

30. 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”

31. 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