I. Case History: Patient demographics: 66 year old Asian female Chief complaint: Dry eyes that are progressively worse throughout the day, which causes major discomfort, foreign body sensation and photophobia. Ocular, medical history: Mild myope with presbyopia, spectacle Rx, no contact lens wear, Cataract extraction with posterior chamber intraocular lens implants both eyes. Patient referred to office for severe non-Sjogren’s keratoconjunctivitis sicca Current ocular medications: Lotemax steroid ophthalmic drops three times per day in both eyes, Systane artificial tears at least 5 times per day in both eyes. History of Nano Tears, Muro 128 hypertonic saline solution, N-acetylcysteine 5%, cyclosporine A and lifitegrast use. Other salient information: Patient has tattoo eyeliner on both upper and lower lid margins of both eyes

II. Pertinent findings: Clinical: Reduced vision, BCVA 20/50 OD, 20/70 OS Conjunctival injection, grade 4+ (severe) interpalpebral superficial keratitis OS worse than OD, several small fine epithelial filaments on the corneal surface OD, 1 medium size epithelial filament and 1 large central epithelial filament with several small fine epithelial filaments OS, minimal meibomian gland expression with severe gland atrophy and tattoo eyeliner along inferior and superior lid margins OU. (will support with pictures) Other: Meibography: Severe grade 4 meibomian gland dropout of both lower lids. (will support with pictures)

III. Differential diagnosis: Primary/leading: Keratoconjunctivitis Sicca with subsequent severe, non-resolving filamentary keratitis Others: Non-autoimmune forms of aqueous deficient dry eye (Keratoconjunctivitis sicca non-Sjogren’s syndrome), Autoimmune related aqueous deficient dry eye (Keratoconjunctivitis sicca, Sjogren’s syndrome), Bacterial keratitis, Viral keratitis, Staph marginal keratitis, Exposure keratopathy, Superior limbic keratoconjunctivitis, Corneal edema, Prolonged occlusion, Cataract surgery, Penetrating keratoplasty, Photorefractive keratectomy, Bell’s Palsy, Neurotrophic keratitis

IV. Diagnosis and discussion: Filamentary keratitis is a severe ocular surface condition that is characterized by “fine strands of degenerated epithelial cells with mucous attached to the cornea (1).” Epithelial damage of the basement membrane causes elevated areas of the cornea allowing for muscin to build up around these elevated areas. This build up creates the filaments, which adhere to the corneal epithelium. The mechanical action of the lids rubbing over the filaments during a blink is what causes the symptoms of pain and subsequent tearing and inflammation. The clinical presentation is classic for mucous filaments on the corneal surface, interpalpebral corneal staining, mucous debris in the inferior cul-de-sac and diffuse conjunctival injection.

V. Treatment, management: Initiate treatment with N-acetylcysteine 10% QID OU, Retaine MGD artificial tears QID OU and Systane lubricating gel QHS OU. Debridement of the filaments with forceps and amniotic membrane transplantation performed OS only. Four days later at the patient’s next follow up, she reports non-compliance with the N-acetylcysteine 10% and states first instillation was that morning. There is complete resolution of filaments and improvement in interpalpebral punctate keratitis OS. Her right eye clinical findings are all unchanged since the previous visit. The amniotic membrane is removed from OS at this office visit. The patient then returns in 14 days. At this visit, the patient is less symptomatic with no filaments OD and trace filaments OS. Interpalpebral staining is still significant OU. At this visit, the amniotic membrane is placed in the right eye due to the significant staining still present OD. The filaments are debrided on the left eye with a bandage contact lens placed afterwards. The patient is scheduled to return in one week from this visit for amniotic membrane and bandage contact lens removal. She is to continue N-acetylcysteine 10% QID OU, Retaine MGD artificial tears QID OU and Systane lubricating gel QHS OU. On the follow up visit for membrane removal OD, there is improvement in staining and new bandage contact lenses are placed OU. The patient reports significant improvement in her symptoms. The patient discussed in this case has severe keratoconjunctivitis sicca, which is most likely due to her nearly total meibomian gland atrophy. Treatment to help her underlying keratoconjunctivitis sicca is aimed at improving her meibomian gland dysfunction (MGD), therefore, Retain MGD artificial tears are prescribed for this patient. Another interesting aspect of this patient’s history is the tattoo eyeliner on the inferior and superior lid margins of both of her eyes. The procedure of micropigmentation of the eyelid margin has been found to be associated with total meibomian gland dropout. It was also found that traditional meibomian gland therapy was not useful on these patients that presented with complete gland atrophy (3). The literature on this subject is variable. As with most ocular diseases, treatment is dependent on the patient and can be quite different when comparing cases. With that said, generally, the most consistent strategies for managing filamentary keratitis include the following: debridement of large filaments, generous lubrication of the ocular surface, and treatment of the underlying cause (2). Debridement is typically performed solely on large filaments and is done with forceps and involves subsequent antibiotic coverage. Lubrication can be done with any type of artificial tear in addition to a gel or ointment at night. Lastly, depending on the patient’s root cause of the filamentary keratitis, the treatment changes in order to control this factor. Additional treatments for severe dry eye syndrome that will be further explored are autologous serum tears and scleral lenses. (treatment and management will be further supported by current research and literature)

Bibliography: (1) Albietz J, Sanfilippo P, Troutbeck R, Lenton L. Management of Filamentary Keratitis Associated with Aqueous- Deficient Dry Eye. Optometry and Vision Science. 2003; 80(6): 420-430. (2) Filamentary Keratitis. Review of Optometry Cornea. June 2015. 31A-32A (3) Kojima T, Dogru M, Matsumoto Y, et al. Tear film and ocular surface abnormalities after eyelid tattooing. Ophthal Plast Reconstr Surg. 2005 Jan; 21(1): 69-71. (4) Harminder S Dua. Amniotic membrane transplantation. British Journal of Ophthalmology. 2017; 83(6). (5) Kabat A, Sowka J. Fighting Filamentary Keratitis. Review of Optometry. Feb 2015. (6) Cremers S. Best Way to Treat Filamentary Keratitis. Fellow of the American Board of Ophthalmology. Sep 2015. (7) Zaldman GW, Geeraets R, Paylor RR, Ferry AP. The histopathology of filamentary keratitis. Arch Ophthalmol. 1985 Aug: 103(8) 1178-81. (8) Kang MH, Kim MK, Lee HJ, Wee WR, Lee JH. Interleukin-17 in various ocular surface inflammatory diseases. J Korean Med Sci. 2011 Jul; 26(7) 938-44.

VI. Conclusion: Filamentary keratitis is a serious clinical finding that is indicative of an extremely compromised ocular surface. Although there are numerous treatment options that can be considered for these patients, the case presented in this report shows that N-acetylcysteine 10% and amniotic membrane transplantation are two treatments that have relatively quick and positive outcomes. The combination of N-acetylcysteine 10% and amniotic membrane transplantation that was used in this case showed to have a rapid response and resolution of the filamentary keratitis. When treating a complex disease such as filamentary keratitis, it is important to explore all options for the patient and tailor the treatment options based on the underlying etiology of the disease.