A Double-Header: Dry Eye and Filamentary Keratitis
AT A GLANCE
- Filamentary keratitis is a common complication of dry eye disease and is characterized by the presence of filaments on the surface of the cornea.
- Treatment modalities emphasize mechanical removal of the filaments, which can cause damage to the ocular epithelium.
- This case demonstrates that treatment using dehydrated amniotic membrane is effective at eliminating the signs and symptoms of dry eye disease.
Filamentary keratitis (FK) is characterized by the presence of filaments on the surface of the cornea and is a common complication of ophthalmic surgery and dry eye disease (DED).1,2 Although the exact prevalence of FK in the United States is unknown, the condition results in approximately 1 million clinic and outpatient visits per year.3 Management of FK varies, but most treatment options address the underlying etiology of the ocular surface abnormality to limit symptoms with the goal of restoring the ocular surface to normal conditions.
In this case report, we present a patient with a history of treatment-resistant severe DED, significant punctate epithelial erosions (PEEs), and FK. Despite previous resistance to topical treatment, the use of dehydrated human amniotic membrane (dHAM) (Opticyte Amniotic Ocular Matrix, Merakris Therapeutics) successfully eliminated symptoms, suggesting that dHAM can be used to promote healing and reepithelialization of the cornea in treatment-resistant cases of DED and FK.
CASE REPORT
A 60-year-old woman was referred to our clinic for evaluation and treatment of severe DED that was resistant to topical therapy. The patient’s ocular medical history was positive for cataract surgery in each eye and a retinal detachment (RD) in the left eye that had previously been repaired by laser and pars plana vitrectomy. On presentation, the patient complained of experiencing a foreign body sensation and light sensitivity in her left eye to a greater degree than her right eye over the past few months.
The patient’s list of medications included lifitegrast ophthalmic solution 5% (Xiidra, Novartis) and loteprednol etabonate ophthalmic suspension 0.25% (Eysuvis, Kala Pharmaceuticals) in each eye, and a lubricating eye drop every 2 hours, or as needed. Additional medications included amlodipine besylate (Norvasc, Viatris), benazepril HCl (Lotensin, Validus Pharmaceuticals), fenofibrate (various), vitamin D3, a glucosamine and chondroitin sulphate formulation (Osteoflex), acetaminophen, and meloxicam (various).
Clinical Findings
Physical examination showed trace blepharitis in each eye and extensive inflammation of the inner lid with 2+ meibomitis and 2+ telangiectasia. Further examination indicated palpebral conjunctivitis with 1+ papillae and 2+ with lissamine green stain. Corneal examination showed 2+ PEE OD and 3+ PEE OS, with 1+ filaments OS and 1+ central epithelial basement membrane dystrophy (EBMD) OS. Tear film was decreased in the left eye compared with the right eye. Entering UCVA at distance was 20/60 OD and 20/300 OS. Pinhole acuities were 20/50 OD and 20/100 OS. Presumptive diagnoses of severe keratoconjunctivitis sicca (KCS), FK, EBMD, and retinal scarring secondary to RD were made for the left eye, with additional diagnoses of meibomian gland dysfunction and pseudophakia in each eye.
The Treatment Plan
The management approach of this patient was complicated; however, the decision was made to use dHAM with bandage contact lenses (BCLs) to accommodate her frequent driving and need to maintain normal cosmesis.
Follow-Up
After 1 week, the patient claimed her left eye felt much better. Her UCVA improved bilaterally to 20/40 OS and pinhole acuity of 20/25 OS. Slit-lamp examination revealed complete resolution of filaments, no staining OD, with only mild EBMD OS, and trace central PEE OS. Meibomitis persisted in all lids. After removal of the BCLs, the treatment plan consisted of twice daily lifitegrast and loteprednol etabonate, along with frequent preservative-free artificial tears OU.
Two weeks later however, the patient returned to the clinic with an increase in dry eye symptoms. On presentation, she had UCVA of 20/50 OD and 20/80 OS with pinhole acuities of 20/25 OD and 20/30 OS. Corneal staining increased to 2+ OD and 3+ OS with 2+ EBMD OS. A second dHAM with BCL was placed in the left eye. Additionally, the left eye was treated with the topical fluoroquinolone antibiotic ofloxacin ophthalmic solution 0.3% (various) and a biologic eye drop that uses a dilution of amniotic membrane components (Regener-Eyes Ophthalmic Solution, Regener-Eyes) three times daily. The right eye was also treated with the biologic eye drops, as well as lifitegrast and loteprednol etabonate twice daily.
After the second dHAM treatment, the patient’s symptoms of DED and FK significantly decreased. After removal of the BCL, the patient was further managed on a combination of biologic eye drops four times daily in each eye, tapered to twice daily, and preservative-free artificial tears. She was also instructed to take an omega-3 supplement (DE3 Dry Eye Omega Benefits, Physician Recommended Nutriceuticals), apply warm compresses, and use a lid cleanser with a hypochlorous acid spray twice daily. Her UCVA has remained stable at 20/30 OU with pinhole acuities of 20/25 OU without recurrence of FK.
DISCUSSION
KCS complicated by FK often requires a lengthy and frustrating treatment course. Current treatment modalities emphasize mechanical removal of the filaments, followed by extensive lubrication, mucolytic agents, punctal occlusion, BCLs, or autologous serum eye drops.2 Although these treatments can reduce symptoms, the process of removing the filaments can cause further damage to the corneal epithelium (Figure).
Furthermore, these treatments do not address the underlying inflammation and fibrosis that seem to drive epithelial damage. Long-term treatments for this underlying inflammation involve the use of topical corticosteroids. Although often effective, these drugs have significant side effects, including glaucoma, ocular infection, cataracts, and delayed wound healing due to inhibition of growth factors critical in reepithelization.
Acetylcysteine 0.3% ophthalmic solution has been used to effectively treat FK.4 Treatment with this drop should be continued for at least 6 weeks; even if the filaments have cleared, continuation is key to avoid recurrence.4 Another agent, N-acetylcysteine, has been used to manage FK when conventional therapies have failed, but it is not commercially available in an ophthalmic solution and must be compounded by a pharmacist.5
Recently, the use of cryopreserved amniotic membranes (CAM) and dHAM is becoming more frequent to treat nonhealing corneal defects. The dry eye amniotic membrane (DREAM) study clearly showed increased rates of wound healing when using amniotic membrane grafts, with reduced fibrosis and increased epithelization after 1 week and 3 months.6 This is further substantiated by findings indicating that amniotic membrane products reduce TGF-Β signaling, epithelial-to-mesenchymal transition, and inflammatory signaling.7
Our case highlights the efficacy of dHAM supplemented with a diluted and buffered amniotic liquid product, such as Regener-Eyes, in the treatment of complicated KCS with FK. Although the patient had several risk factors for DED prior to her ocular surgeries, she was not diagnosed with DED prior to having cataract surgery. Her predisposing factors for DED include age greater than 40 years, female sex, and breast cancer treated with combination chemotherapy and radiation. Her two previous ocular surgeries, combined with her likely undiagnosed DED, led to the development of poor visual acuity and significant eye discomfort.8,9
Although some clinical guidelines suggest using CAM in the early treatment of advanced DED, dHAM was chosen to treat this patient.10,11 She needed to be able to drive herself to work and perform in a public-facing customer service capacity, and this option gave her excellent cosmesis as well as improved peripheral vision. Some cryopreserved membranes, although effective, can cause significant discomfort due to irritation caused by the outer ring.11
After two 7-day treatments with dHAM, followed by long-term treatment with amniotic membrane extract drops, our patient’s symptoms of FK and DED had largely resolved. This suggests that dHAM is effective at eliminating the signs and symptoms of this disease, likely through potent antiinflammatory action, coupled with reduced TGF-ß signaling. Although some initial studies have shown different concentrations of biologically active molecules in CAM compared to dHAM, more studies are required to elucidate whether these differences affect clinical outcomes.
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