FILAMENTARY KERATITIS

Signs and Symptoms

Patients with filamentary keratitis typically present with variable reports of ocular discomfort, ranging from grittiness and mild foreign body sensation to pronounced pain. Tearing, photophobia and blepharospasm may accompany these symptoms in more severe cases.1 The condition may be unilateral or bilateral, depending upon the underlying etiology. Associated signs include ocular hyperemia, particularly in the limbal area, as well as a pseudoptosis. The hallmark finding is the presence of corneo-mucus filaments. These often consist of a focal “head,” which may be firmly adherent to compromised areas of the corneal epithelium, and a strand-like “tail” of varying length that extends inferiorly across the ocular surface. Filaments can be seen more readily on biomicroscopy with the application of vitals dyes such as lissamine green, rose bengal and sodium fluorescein.1 Other ocular findings that may accompany filamentary keratitis include a reduced tear break-up time (TBUT) and punctate epithelial keratopathy.

While the exact prevalence of filamentary keratitis is unknown, evidence suggests that this condition is more common in elderly patients, women, those with connective tissue disorders and those with immune deficiency.1,2 Coincidentally, these same populations tend to demonstrate a greater incidence of keratoconjunctivitis sicca and other ocular surface disorders. The condition also may develop in those taking systemic medications that have the capacity to diminish aqueous tear production, such as antihistamines, diuretics, mood stabilizing agents and certain antineoplastic agents.1,4

Pathophysiology

Filamentary keratitis is seen most commonly in association with advanced dry eye disease, though a variety of other ocular surface disorders can induce this condition.2 Among the various etiologies are superior limbic keratoconjunctivitis (SLK) of Theodore, herpetic keratitis, recurrent corneal erosion, vernal keratoconjunctivitis, neurotrophic keratitis, epitheliopathy due to aerosol exposure, radiation keratitis, bullous keratopathy, a recent history of cataract or other ocular surgery, prolonged eye patching, blepharospasm and even large-angle strabismus.1-3,5,6

Research suggests that individual filaments consist of desquamated corneal epithelial cells at their core, surrounded primarily by degenerating conjunctival epithelial cells entwined in a thick layer of membrane-associated mucins, including MUC5AC and MUC16.4,7 Subjects with filamentary keratitis appear to suffer progressive dysfunction within the basal epithelial and Bowman’s layers of the cornea, leading to focal detachments at the level of the basement membrane. Under constant shear pressure from the eyelids, these corneal foci become inflamed, and sloughing of epithelial cells may ensue. At the same time, frictional stress from blinking and eye movement, combined with diminished tear volume and ocular surface inflammation, results in abnormal tear mucin production and degeneration of conjunctival epithelial cells.6 These combined elements form filaments that may be seen clinically as long strands, large clumps or irregular dendriform deposits, depending upon whether they are stretched, twisted or tightly coiled.7,8 The filaments are motile in the tear film but have an affinity for compromised areas of the corneal surface, where they form strong adhesions. Lid movement across these bound filaments induces vertical traction and further shearing of the corneal epithelium with each blink, resulting in microtrauma and stimulation of the pain-sensitive corneal nerves. Thus, a vicious cycle of epithelial damage, inflammation and filament formation ensues.

Management

The management of filamentary keratitis is aimed at alleviating the stressors that cause ocular surface inflammation and epithelial degradation. Elimination of the filaments is the initial step. Identifying and treating the underlying pathology is also vital to break the disease cycle. Removal of large filaments can be performed mechanically using fine-tipped forceps at the slit lamp under topical anesthesia; however, it is important to realize that this process can further contribute to epithelial damage and should be undertaken only by skilled and experienced clinicians. Bandage soft contact lenses can be used in cases where the clinician wishes to avoid manually debriding the tissue tags.

Ocular lubricants are helpful in addressing discomfort and also stabilizing the tear film in mild to moderate cases. While some have advocated hypertonic saline, other practitioners (including these authors) prefer lipid-based artificial tears as first-line therapy.9,10 In more recalcitrant cases, topical N-acetylcysteine can help to dissolve cornea-bound mucus plaques.2 This mucolytic agent is typically employed as an oral inhalant for patients with bronchial disease (e.g., emphysema, cystic fibrosis), in accordance with its FDA approval. Acetylcysteine solution must be prepared by a compounding pharmacist when prescribed for off-label topical ophthalmic use. In those with filamentary keratitis secondary to chronic dry eye disease, 5% to 10% acetylcysteine eye drops used at least four times daily may be very effective in reducing or eliminating the mucus strands and plaques. Other treatments for refractory cases of filamentary keratitis may include the use of bandage soft contact lenses, amniotic membrane therapy or Botox (onabotulinumtoxin A, Allergan) injection to the pretarsal orbicularis muscle.1,3,11

Addressing the underlying ocular surface disease may ultimately prove more challenging than temporary elimination of corneal filaments. Because an inflammatory etiology is often assumed, the use of anti-inflammatory pharmaceuticals such as corticosteroids and non-steroidal agents has been widely advocated, often with clinical success.5,9,12 In those cases where dry eye disease is determined to be the primary etiology of filamentary keratitis, short-term use of topical corticosteroids QID combined with long-term use of topical cyclosporin A BID has been shown to be helpful.13 Punctal plugs may also be employed for those with true aqueous deficiency.1 More severe cases may require treatment with autologous serum eye drops, which, as the name implies, are derived from the patient’s own blood serum.14,15

Clinical Pearls

Despite the fact that the condition has a unique ICD-9 code (370.23), filamentary keratitis is not a disease entity in and of itself. Rather, it should be considered a sign of severe ocular surface disease, the etiology of which must ultimately be determined and addressed for successful long-term management of the patient.

Topical 10% acetylcysteine QID is often a helpful adjunct in managing filamentary keratitis. Patients should be advised that this solution may have an unusual color, a peculiar odor and a tendency to sting unless it is kept refrigerated. Also, because it is formulated without preservatives, topical ophthalmic acetylcysteine must be discarded after approximately 60 days. The recommendation to employ acetylcysteine drops is based upon clinical experience of several noted experts and the underlying pathophysiology of filament formation. There are currently no prospective, controlled clinical studies to substantiate this practice, however.

While not commercially available in the United States, a 5% acetylcysteine solution is currently being manufactured by the French company Laboratories Pharmaster, and marketed by Moorfields Pharmaceuticals in the United Kingdom, under the trade name Ilube. In addition to acetylcysteine, this product contains purified water, hypromellose, sodium hydroxide, disodium edetate and benzalkonium chloride as a preservative.16

Therapy for filamentary keratitis may take weeks or even months before adequate resolution is realized; the time depends greatly upon the etiology, the severity of the presentation and the aggressiveness of care. Affected patients should understand that the underlying condition is often chronic and filaments may recur, requiring ongoing therapy.

Patients found to have aqueous-deficient dry eye disease in association with filamentary keratitis may benefit from investigation for rheumatologic involvement, such as the Sjö test. Eye care providers can use this point-of-care diagnostic test to help to identify Sjögren’s syndrome in patients who might otherwise go undiagnosed for months or years.17

1. Diller R, Sant S. A case report and review of filamentary keratitis. Optometry. 2005;76(1):30-6.

2. Albietz J, Sanfilippo P, Troutbeck R, Lenton LM. Management of filamentary keratitis associated with aqueous-deficient dry eye. Optom Vis Sci. 2003;80(6):420-30.

3. Gumus K, Lee S, Yen MT, Pflugfelder SC. Botulinum toxin injection for the management of refractory filamentary keratitis. Arch Ophthalmol. 2012;130(4):446-50.

4. Kawakami H, Sugioka K, Yonesaka K, et al. Human epidermal growth factor eyedrops for cetuximab-related filamentary keratitis. J Clin Oncol. 2011;29(23):e678-9.

5. Perry HD, Doshi-Carnevale S, Donnenfeld ED, Kornstein HS. Topical cyclosporine A 0.5% as a possible new treatment for superior limbic keratoconjunctivitis. Ophthalmology. 2003;110(8):1578-81.

6. Kakizaki H, Zako M, Mito H, Iwaki M. Filamentary keratitis improved by blepharoptosis surgery: two cases. Acta Ophthalmol Scand. 2003;81(6):669-71.

7. Tabery HM. Filamentary keratopathy: a non-contact photomicrographic in vivo study in the human cornea. Eur J Ophthalmol. 2003;13(7):599-605.

8. Pandit RT. Dendriform filamentary keratopathy. Cornea. 2009;28(1):123-5.

9. Avisar R, Robinson A, Appel I, et al. Diclofenac sodium, 0.1% (Voltaren Ophtha), versus sodium chloride, 5%, in the treatment of filamentary keratitis. Cornea. 2000;19(2):145-7.

10. Greiner JV, Korb DR, Kabat AG, et al. Successful treatment of chronic idiopathic recurrent filamentary keratopathy using a topical oil-in-water emulsion: A report of 5 cases. Poster presented at the 25th Biennial Cornea Research Conference. Boston, MA. October 11-13, 2007.

11. Suri K, Kosker M, Raber IM, et al. Sutureless amniotic membrane ProKera for ocular surface disorders: short-term results. Eye Contact Lens. 2013;39(5):341-7.

12. Coursey TG, de Paiva CS. Managing Sjögren’s syndrome and non-Sjögren syndrome dry eye with anti-inflammatory therapy. Clin Ophthalmol. 2014;8:1447-58.

13. Sheppard JD, Donnenfeld ED, Holland EJ, et al. Effect of loteprednol etabonate 0.5% on initiation of dry eye treatment with topical cyclosporine 0.05%. Eye Contact Lens. 2014;40(5):289-96.

14. Jirsova K, Brejchova K, Krabcova I, et al. The application of autologous serum eye drops in severe dry eye patients; subjective and objective parameters before and after treatment. Curr Eye Res. 2014;39(1):21-30.

15. Hussain M, Shtein RM, Sugar A, et al. Long-term use of autologous serum 50% eye drops for the treatment of dry eye disease. Cornea. 2014;33(12):1245-51.

16. ILUBE [package insert]. Moorfields Eye Hospital NHS Foundation Trust trading as Moorfields Pharmaceuticals; London, United Kingdom; 2010.

17. Shen L, Kapsogeorgou EK, Yu M, et al. Evaluation of salivary gland protein 1 antibodies in patients with primary and secondary Sjogren’s syndrome. Clin Immunol. 2014;155(1):42-6.