Alternative for Filamentary Keratitis
Filamentary Keratitis & Best Way to Treat Filamentary Keratitis
Filamentary Keratitis is due to a damaged epithelial or Bowman’s layer of the cornea. A combination of factors (ie, aqueous tear deficiency, mucin deficiency, meibomian gland/oil irregularities, as well as viruses in some cases) combined with the shearing of the eyelids can lead to a vicious cycle of epithelial damage, inflammation, and filament formation which can be very painful.
Causes of Filamentary Keratitis:
1. #1 is Dryness or Irregularity of the tear film, such as from
a. Meibomian Gland Dysfunction: oil glands at base of eyelashes are clogged
b. Sjögren’s syndrome: immune system dysfunction that can cause dry mouth & arthritis & dry eyes
2. Too Tight Contact Lenses
3. Graft Versus Host Disease
4. Viruses: FK can occur in EKC-Epidemic Keratoconjunctivitis
5. Chemical exposure or previous chemical exposure.
6. Any ocular procedure: Surgical procedures, such as corneal transplants (penetrating keratoplasty), cataract surgery, and keratorefractive surgery like LASIK or PRK, can have adverse effects on corneal innervation, tear secretion, and ocular surface health. These procedures have the potential to produce filament formation in patients with tear film and/or ocular surface problems.
We use a tiered approach and recommended the following first steps. If no improvement seen with first treatments, we proceed to higher tiered treatments.
1. Frequent debridement: we will see a patient every 3-6months and as needed if pain continues to recur from the filament formation.
2. Nonpreserved Artificial Tears 4-8x/day and nonpreserved gels at night at least: best are ones with Sodium hyaluronate and/or polyacrylic acid (carbomer); Preservatives in artificial tears and other drops can make FK worse. Thus avoid ophthalmic preservatives, such as benzalkonium chloride, chlorobutanol, and thimerosal.
3. Meibomian Gland Lid Hygiene: see eyedoc2020@blogspot.com “Lid Hygiene”
3. Meibomian Gland Lid Hygiene: see eyedoc2020@blogspot.com “Lid Hygiene”
4. Diclofenac sodium 0.1% drops and/or gel (Voltaren) 4x/day often helps FK.
5. Hypertonic Saline like Muro 128 drops 4x/day and ointment at night which promotes adherence of the epithelial cells on the surface to the underlying corneal tissue and, hence, prevents formation of new receptor sites for filament formation.
5. Hypertonic Saline like Muro 128 drops 4x/day and ointment at night which promotes adherence of the epithelial cells on the surface to the underlying corneal tissue and, hence, prevents formation of new receptor sites for filament formation.
6. Mucolytic Agents: 10% acetylcysteine N-acetylcysteine (Mucomyst 20% is diluted to a 10% solution with artificial tears. Use of this medication dissolves mucous plaques: kept refrigerated; stable for only 60 days. This is ordered from a compounding pharmacy:
Foer’s pharmacy locations on website:
Foer’s pharmacy locations on website:
7. Punctal Plugs: can be temporary or permanent
8. Therapeutic bandage contact lens
9. Autologous serum: 4x/day or more if nonpreserved
10. Topical steroids if none of the above are helping: start with lease strong & move to stronger steroids if needed (Lotemax/Alrex<FML mild<FML,Predforte<Durezol)
11. In GVHD patients or severe Sjögren’s syndrome we recommend oral tacrolimus and prednisolone therapy.
12. Continue to look out for any signs of Herpes Zoster: treat with anti-virals if dendrites noted.
13. Excimer Laser Phototherapeutic Keratectomy (PTK) helps in some patients unresponsive to above.
14. Botox injection to help decrease mechanical rubbing of eyelid against cornea.
12. Continue to look out for any signs of Herpes Zoster: treat with anti-virals if dendrites noted.
13. Excimer Laser Phototherapeutic Keratectomy (PTK) helps in some patients unresponsive to above.
14. Botox injection to help decrease mechanical rubbing of eyelid against cornea.
Corneal filaments or plaques generally only last a few days to a few weeks; however, they can reoccur but usually not in the same location.
Mechanism: A Vicious Cycle of Inflammation:
What happens is:
1. Some injury or dryness causes a focal areas of basement membrane detachment on the Corneal Epithelium
2. Then the shearing force of the eyelids causes these elevated epithelial areas to increase with time.
3. These elevated epithelial foci bind with mucin strands and degenerated epithelial cells, forming long filaments.
4. Each blink results in epithelial tearing, ocular pain, and chronic inflammation because the filaments are firmly attached to the underlying epithelium,
5. This leads to reflex blinking that leads to a vicious cycle on the ocular surface.3 Therefore, breaking this vicious cycle is important for managing challenging cases of filamentary keratitis.
Sandra Lora Cremers, MD, FACS
More information below:
Filamentary Keratitis
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Disease Entity[edit source]
Filamentary Keratitis ICD-9 370.23
Disease[edit source]
Filamentary keratitis is a condition in which strands (“filaments”) composed of degenerated epithelial cells and mucus develop on and adhere to the corneal surface causing pain and foreign body sensation.
Etiology[edit source]
The etiology of filamentary keratitis is related to an alteration in the components of the tear film and/or abnormalities of the corneal surface. It is associated with a number of ocular surface diseases and conditions.
Risk Factors[edit source]
Any alteration of the tear film or corneal surface can increase the risk for filamentary keratitis. Common risk factors include: aqueous tear deficiency as in keratoconjunctivitis sicca, corneal exposure (e.g. seventh nerve palsy), occlusion abnormalities such as blepharoptosis, ocular surgery (e.g. keratoplasty), systemic diseases with effects on the ocular surface (e.g. Sjogren’s syndrome ), extended use of anticholinergic medications, and other ocular surface abnormalities.
General Pathology[edit source]
In filamentary keratitis, there is often an increase in the tear film mucus to aqueous ratio. This is commonly due to a decrease in aqueous tear production, but may also be due to increased production or accumulation of the mucinous component. This alteration in tear film makeup sets the stage for formation of mucoid filaments. Small defects in the corneal epithelium provide an anchoring surface for the filaments. Mucin attaches to the epithelial defect and loose epithelial strands are incorporated into the mucin strand attached to the surface. Filaments may be small sessile adhesions or longer strings that cause irritation and discomfort.
Pathophysiology[edit source]
It is hypothesized that the initial step in the development of filamentary keratitis is damage to basal epithelial cells, epithelial basement membrane, or Bowman’s layer leading to focal detachments of the epithelial basement membrane. Blinking causes these areas of detachment to become elevated leading to irritation, inflammation, and increased mucus production. The sites of epithelial damage provide the scaffold for filaments to develop. A postmortem analysis of a cornea in a patient with this condition revealed inflammatory cells and fibroblasts just beneath the basal epithelium.
Primary prevention[edit source]
Filamentary keratitis generally occurs in association with an underlying condition. The primary preventative measure is lubrication in the setting of dry eye.
Diagnosis[edit source]
History[edit source]
Patients with filamentary keratitis complain of foreign body sensation. They may also have redness, epiphora, blepharospasm, and photophobia.
Physical examination[edit source]
Slit lamp examination reveals filaments (‘mucoepithelioid” strands) adherent to the corneal surface. The filaments can vary from 0.5mm to 10mm in length. A gray colored subepithelial opacity can sometimes be seen at the base of the filament. Blinking causes painful traction on the filaments and may detach them, leaving behind an epithelial defect. Filaments stain best with rose Bengal , but can be seen with fluorescein as well. The location of the filaments can help determine the underlying cause. Filaments due to dry eye syndromes tend to be found in the interpalpebral space, those due to ptosis superiorly, and those due to surgery at the site of the wound or surgical trauma
Signs[edit source]
Signs include multiple filamentary attachments firmly adherent to the corneal surface, decreased aqueous tears, increased mucin in the precorneal tear film, subepithelial opacities at the base of filaments, or frank corneal epithelial defects.
Symptoms[edit source]
Symptoms can vary from mild to severe foreign body sensation that is exacerbated by blinking and is associated with photophobia, blepharospasm, and epiphora. The patient may also complain of a red eye.
Clinical diagnosis[edit source]
The diagnosis of filamentary keratitis is made clinically with history and slit lamp biomicroscopy.
Diagnostic procedures[edit source]
Slit lamp biomicroscopy demonstrates firmly adherent filaments on the corneal surface. A Schirmer test may be helpful in establishing the diagnosis of a dry eye syndrome.
Laboratory test[edit source]
There is no specific laboratory testing indicated for filamentary keratitis. However, if suspicion is high for underlying systemic disease that has not yet been diagnosed such as Sjogren’s syndrome, a systemic work-up may be indicated.
Differential diagnosis[edit source]
Management[edit source]
General treatment[edit source]
The treatment of filamentary keratitis can be challenging and is often chronic. Paramount in the overall treatment of filamentary keratitis is management of underlying conditions such as the dry eye syndromes, medication toxicity, contact lens overuse, and blepharoptosis.
Medical therapy[edit source]
Medical follow up[edit source]
Patients should be re-examined 3-4 weeks after the initiation of medical therapy. Bandage contact lenses should be left in place for no more than one month.
Surgery[edit source]
Filaments can be removed at the slit lamp using jeweler’s forceps. Care should be taken to avoid disrupting the epithelium at the base of the filament if possible. Manual removal of the filaments may help in alleviating symptoms temporarily but is only a temporizing measure and is not successful without concurrent medical treatment. Punctal occlusion may also be helpful in cases of underlying aqueous tear deficiency.
Complications[edit source]
Prognosis[edit source]
References[edit source]
Davidson RS, Mannis MJ. Filamentary Keratitis. In: Krachmer JH, Mannis MJ, Holland EJ, editors. Cornea. Vol 1. 3rd ed. Philadelphia: Elsevier/Mosby; 2011. P. 1093-96.
Van Meter WS, Katz D, Cook BG. Filamentary Keratitis. In: Holland EJ, Mannis MJ, Lee WB, editors. Ocular Surface Disease: Cornea, Conjunctiva , and Tear Film. Philadelphia: Elsevier Saunders; 2013. P. 213-16.
Zaidman GW, Geeraets R, Paylor RR, et al. The histopathology of filamentary keratitis. Arch Ophthalmology 1985; 103: 1178-81.
Tanioka H, Yokoi N, Komuro A, et al. Investigation of the corneal filament in filamentary keratitis. Invest Ophthalmol Vis Sci 2009; 50:3696-702.
Botulinum Toxin Injection for the Management of Refractory Filamentary Keratitis FREE
ABSTRACT
Objective To evaluate the efficacy of onabotulinumtoxinA injection for the treatment of refractory filamentary keratitis.
Methods A retrospective review of treatment response of 33 eyes of 17 patients with filamentary keratitis resistant to conventional medical therapy who were treated with onabotulinumtoxinA injection was performed. Ocular surface findings, symptom improvement, and the number and location of filaments before and after the injections were recorded. All eyelids were injected subcutaneously with onabotulinumtoxinA (10 U/0.1 mL). All treatments were performed in accordance with an individualized treatment plan using precise localizing treatment maps, with adjustments to dosage based on treatment response.
Results Objective and subjective improvement was noted after the initial onabotulinumtoxinA injection in all patients. Filaments completely resolved after the onabotulinumtoxinA injection in 29 eyes (88%). In 20 of these eyes, filaments and punctate fluorescein staining resolved, whereas in 9 eyes, filaments resolved but punctate fluorescein staining persisted. Three eyes (9%) had partial improvement: 2 residual microfilaments were noted in one eye and 1 in the other eye. In 1 eye, filaments resolved after initial and subsequent injections but recurred within 8 weeks of each injection. Although 14 treated eyes (42%) showed sustained improvement after 1 onabotulinumtoxinA injection, additional injections were necessary in 19 eyes (58%) during the follow-up period because of the recurrence of symptoms and filaments on the cornea.
Conclusions OnabotulinumtoxinA injection should be considered an effective option for treating refractory filamentary keratitis. Because of the likelihood of recurrence, serial onabotulinumtoxinA injections may be necessary in some cases.
Filamentary keratitis is a chronic and recurrent disorder of the cornea characterized by the formation of epithelial and mucous filaments on the corneal surface.1,2 This condition is more common in women and elderly individuals and may be seen either unilaterally or bilaterally, depending on the underlying cause. Patients with filamentary keratitis generally experience foreign-body sensation, chronic pain, tearing, mucoid discharge, photophobia, and blepharospasm.
Even though filamentary keratitis most often accompanies dry eye, especially aqueous tear deficiency, it may also be associated with various other ocular surface diseases, including superior limbic keratoconjunctivitis, viral keratoconjunctivitis, prolonged patching after any ocular surgery, penetrating keratoplasty, ptosis, recurrent corneal erosion, neurotrophic keratitis, and bullous keratopathy.1,3– 5
Conventional treatment of filamentary keratitis involves mechanical removal of the filaments and therapies to decrease inflammation and lubricate the ocular surface. Unfortunately, conventional treatment modalities may not produce sufficient improvement in some cases, leading ophthalmologists to explore the effectiveness of alternative treatments. The best example of an alternative treatment was the successful use of blepharoptosis surgery to treat filamentary keratitis.6,7 The purpose of our study was to determine whether injection of onabotulinumtoxinA (BOTOX; Allergan Pharmaceuticals), another alternative treatment modality, might effectively eliminate filaments in cases that are refractory to conventional therapy.
This retrospective medical record review was approved by the Baylor College of Medicine Institutional Review Board. The research protocol adhered to the tenets of the Declaration of Helsinki for clinical research.
STUDY POPULATION
The medical records of 17 patients (33 eyes) with a history of filamentary keratitis resistant to conventional medical therapy were reviewed. Information regarding the type of tear dysfunction, previous treatments, number and location of filaments, and type and outcome of therapy were recorded.
BOTULINUM TOXIN INJECTION
OnabotulinumtoxinA was reconstituted with sterile, nonpreserved normal saline to achieve a concentration of 10 U/0.1 mL. The area to be injected was prepared with isopropyl alcohol. All injections were administered into the pretarsal orbicularis near the eyelid margin of the upper and lower eyelids. Patients were usually given 2 injections into each eyelid with a dosage of 2 to 5 U of onabotulinumtoxinA per eyelid. All treatments were performed in accordance with an individualized treatment plan using precise localizing treatment maps, with adjustments to dosage based on treatment response. Patients were reevaluated at 6- to 12-week intervals, and injections were administered again at these visits, if needed. After the injection, all patients continued with their previous medical treatment during the follow-up period.
The Table summarizes demographic information, clinical features, and prior treatment of patients who received onabotulinumtoxinA injection. The mean (SD) age of the 17 patients treated (13 women and 4 men) was 65.3 (12.5) years (range, 42-89 years). All patients were followed up at regular intervals of 6 to 12 weeks after the injection. Relative to the first injection, mean follow-up duration was 26.8 months per eye (range, 1-45 months).
Objective and subjective improvement was observed after the initial onabotulinumtoxinA injection in all patients. Filaments completely resolved after either single or additional onabotulinumtoxinA injections in 29 eyes (88%). In 20 of these eyes, filaments and punctate epithelial fluorescein staining resolved; however, in 9 eyes, filaments resolved but punctate epithelial fluorescein staining was noted to persist. Only 3 eyes (9%) revealed partial healing; 2 had only 1 tiny filament and 1 had microfilaments. In the left eye of patient 3 (Table), filaments resolved after initial and subsequent injections but recurred within 12 weeks of each injection.
Although 14 treated eyes (42%) showed sustained improvement after 1 onabotulinumtoxinA injection, additional injections were necessary in 19 eyes (58%) during the follow-up period due to the recurrence of symptoms and corneal filaments. The mean (SD) number of injections was 3.9 (2.5) (range, 2-10). No significant adverse effects were found secondary to the injection of onabotulinumtoxinA in any patient during the follow-up period.
No significant correlation was found between the number of injections with age or the underlying cause of filamentary keratitis (Spearman correlation test, P = .60).
Images taken before and 6 weeks after the initial onabotulinumtoxinA injection in a 76-year-old woman (patient 3) with filamentary keratitis, who had secondary Sjögren syndrome, are shown in the Figure. These images are representative of the outcome achieved with onabotulinumtoxinA injections. Recurrent filaments were noted 12 weeks after the first and second injections in the left eye, which had more severe keratoconjunctivitis sicca and photophobia.
Figure. Slitlamp photography of the left eye. Images without (A and B) and with (C and D) fluorescein staining before (A and C) and 6 weeks after (B and D) the initial onabotulinumtoxinA injection in a 76-year-old woman (patient 3) with filamentary keratitis who had secondary Sjögren syndrome. Filaments completely disappeared after the first and second onabotulinumtoxinA injections but were noted to recur by 12 weeks after each injection.
This study evaluated the efficacy of onabotulinumtoxinA injection in the treatment of refractory filamentary keratitis. Botulinum toxin is a neurotoxin that prevents the release of acetylcholine into the neuromuscular junction, resulting in paralysis of the injected muscle.8 OnabotulinumtoxinA is a formulation of type A botulinum toxin that has been approved by the US Food and Drug Administration since 1989 for the treatment of essential blepharospasm and hemifacial spasm. We chose to use onabotulinumtoxinA in this study because of our extensive experience with the medication and our familiarity with the dosing, efficacy, and potential complications of the injections.
In our study, objective and subjective improvement was achieved in almost all of the treated patients. Filaments completely resolved after either single or multiple onabotulinumtoxinA injections in 29 eyes (88%). Because of the chronic and recurrent nature of this condition, additional onabotulinumtoxinA injections were necessary to maintain the treatment effect in most cases. Even though adverse events, including lack of effect, injection site reaction, eyelid ptosis, diplopia, or lagophthalmos, have been reported in the literature, no clinically significant adverse events were noted in our case series.9
Ideally, treatment of filamentary keratitis should target the underlying pathophysiologic mechanism. However, the exact pathogenesis of filament formation has not been established. Zaidman and colleagues2hypothesized that underlying causes lead to focal areas of basement membrane detachment. After this initial step, the shearing force of the eyelids contributes to the elevation of these epithelial foci with time.2 Finally, the elevated epithelial foci bind with mucin strands and degenerated epithelial cells, forming long filaments.2 Because the filaments are firmly attached to the underlying epithelium, each blink may result in epithelial tearing, ocular pain, and chronic inflammation, which, in turn, stimulates reflex blinking that leads to a vicious cycle on the ocular surface.3 Therefore, breaking this vicious cycle is important for managing challenging cases of filamentary keratitis.
A treatment strategy involves eliminating the mucous filaments as thoroughly as possible and improving ocular surface health.3 Filaments can be eliminated mechanically or pharmaceutically. Mechanical removal can be performed with jeweler’s forceps10 or a cellulose acetate filter.11 Hypertonic saline12,13 and mucolytic agents14 have been successfully used in the treatment of filamentary keratitis.3 Hypertonic saline is believed to promote adherence of the epithelial cells on the corneal surface by extracting fluid from the cornea and preventing formation of new receptor sites for filament formation. N -acetylcysteine, a mucolytic agent, used primarily as an inhalant for patients with bronchial disease, effectively dissolves corneal filaments when applied topically in a 2% to 10% solution.3 Additional treatment strategies include the use of preservative-free artificial tears, elimination of toxic or preserved topical medications, punctal occlusion, and use of anti-inflammatory agents.
Anti-inflammatory agents, including nonsteroidal anti-inflammatory agents and corticosteroids, may break the vicious cycle in some cases of the filamentary keratitis. In one retrospective study, Marsh and Pflugfelder15 reported that topical treatment with the preservative-free corticosteroid methylprednisolone improved irritation symptoms and resolved filamentary keratitis in a series of patients with severe keratoconjunctivitis sicca. In addition, some studies13,16 have reported the successful use of topical nonsteroidal anti-inflammatory agents, such as 0.1% diclofenac sodium, in the treatment of challenging filamentary keratitis. Avisar and colleagues13 compared the efficacy and short-term safety of 0.1% diclofenac sodium and 5% hypertonic saline ophthalmic solution in the treatment of filamentary keratitis associated with secondary Sjögren syndrome. They concluded that patients treated with this nonsteroidal anti-inflammatory drug had more rapid improvement in clinical symptoms than those treated with 5% hypertonic saline solution.
Although certain contact lenses, particularly conventional hydrogel lenses with low oxygen permeability, have been reported to cause filamentary keratitis,17 therapeutic bandage contact lenses have been successfully used to treat filamentary keratitis.18 The Boston Ocular Surface Prosthesis (Boston Foundation for Sight), with its unique fluid-filled reservoir, may also protect the cornea from blink trauma in challenging filamentary cases.
In our case series, as indicated in the Table, the underlying causes of refractory filamentary keratitis included blepharospasm, superior limbic keratoconjunctivitis, and severe keratoconjunctivitis sicca. All these conditions are related in that they are associated with blink-related microtrauma.4 In superior limbic keratoconjunctivitis, corrugations parallel to the upper eyelid margins can be observed due to redundant superior bulbar conjunctiva; in contrast, horizontal conjunctival folds may occur along the eyelid margins in eyes with severe keratoconjunctivitis sicca.19– 21 In both situations, the eyelid movement during each blink traumatizes the ocular surface, which in turn leads to a vicious frictional cycle on the cornea that may predispose patients to formation of filaments. The frictional component is exacerbated by tear deficiency and accompanying ocular surface epithelial changes, such as conjunctival squamous metaplasia and goblet cell loss. Increased eyelid friction is the most likely mechanism for filaments associated with eyelid ptosis, where the eyelid margin and a portion of the tarsal conjunctiva are in constant contact with the superior cornea. Resolution of filaments after ptosis repair suggests that reducing the extent of eyelid friction can break the cycle.6,7 This mechanism served as our rationale for using onabotulinumtoxinA to treat filaments. Relaxation of the orbicularis muscle would be expected to decrease eyelid pressure on the cornea and blink frequency and force. The treatment outcomes clearly support this mechanism. However, our findings indicate that filaments are more likely to recur in eyes with more severe tear deficiency as the relaxing effect of onabotulinumtoxinA on eyelid pressure wanes.
In summary, onabotulinumtoxinA injection was performed in challenging cases of filamentary keratitis that did not improve with conventional treatments. Both subjective and objective outcomes were impressive, with resolution of filaments after onabotulinumtoxinA injection in 88% of eyes. No serious clinical events related to onabotulinumtoxinA injections were reported during the follow-up period. Perhaps the biggest deficiency of this novel treatment for filamentary keratitis is the need for additional injections to maintain the therapeutic effect. The mean number of injections per person was almost 4 in this case series. No prospective studies on the effects of onabotulinumtoxinA injections on filamentary keratitis have been reported to date. Larger, prospective, randomized trials are needed to verify our preliminary observations.
