Man experiences decreased vision, irritation after contact lens misuse
A 58-year-old man who lives out of state had a history of waking up with irritation in his right eye 2 weeks after sleeping in his contact lenses.
His medical history was significant for type 2 diabetes, hypertension, hyperlipidemia, morbid obesity, obstructive sleep apnea, recurrent deep venous thrombosis, daily alcohol consumption and cannabis use. He was treated initially by his optometrist with a trial of neomycin, polymyxin B, dexamethasone and ketorolac drops for pain relief for corneal abrasion, which was then switched to ciprofloxacin for infectious keratitis. Corneal swab was positive for Staphylococcus epidermidis. He subsequently was evaluated by a cornea specialist after worsening of the stromal suppuration and development of a partial ring infiltrate and a small hypopyon. He was started on fortified vancomycin and fortified tobramycin every hour. There was minimal clinical improvement on 5 days of fortified antibiotics with visual acuity of hand motion, IOP of 33 mm Hg and a negative repeat culture. The patient was started on IOP-lowering therapy, continued the antibiotic regimen and was referred to the cornea department of the New England Eye Center.
Source: William W. Binotti, MD, and Azin Abazari, MD
Examination
On our exam, 6 weeks after initial presentation, the patient’s ocular pain persisted, visual acuity was hand motion in the right eye, and IOP was 24 mm Hg on a combination of brinzolamide and brimonidine twice daily, timolol twice daily, latanoprost every night at bedtime and oral acetazolamide 1,000 mg. Exam was notable for a 6.9 mm × 7.3 mm epithelial defect, diffuse stromal infiltrate and a 4-mm layered hypopyon; there were no signs of corneal perforation (Figure 1). There was no growth on the previous culture. B-scan showed no signs of endophthalmitis, and the retina was attached (Figure 2a). In vivo confocal microscopy (IVCM) showed the presence of extensive inflammatory cells throughout the entire cornea, loss of corneal nerves, a disorganized stroma, and no signs of cysts, trophozoites, filaments or hyphae (Figure 2b).
Given the findings, the patient was started on valacyclovir 500 mg three times a day for possible herpes keratitis, doxycycline 100 mg twice daily and oral vitamin C 1 g daily to reduce corneal inflammation and risk for perforation, and oral gabapentin for pain with close follow-up with provider. The patient was referred back to our service the following week due to worsening signs and symptoms. His vision was now light perception, IOP was 23 mm Hg, and there was a complete epithelial defect (10 mm × 10 mm) and total hypopyon (Figure 3). Repeat B-scan showed no signs of endophthalmitis.
What is your diagnosis?
See answer below.
Contact lens misuse
At initial presentation, one should always keep a broad differential diagnosis, such as infectious causes, inflammatory causes (eg, Mooren’s ulcer, peripheral ulcerative keratitis, interstitial keratitis), and toxic or traumatic causes (eg, corneal abrasion or foreign body, chemical injury, medicamentosa). In this case with central corneal infiltrate, epithelial defect and hypopyon, infectious keratitis was at the top of the list. Thus, performing corneal cultures and starting fortified antibiotics empirically was warranted. For patients who do not improve or worsen on fortified antibiotics, there should be a high suspicion for infectious causes other than bacteria (eg, Acanthamoeba, fungus, viruses).
In this case, the initial corneal culture media grew S. epidermidis. Because the patient was not responding to treatment, his cornea was cultured again, a corneal swab was sent for polymerase chain reaction (PCR), and he underwent IVCM. These were not revealing. Thus, given continued worsening on fortified antibiotic therapy with complete epithelial defect and hypopyon as well as elevated IOP on maximum therapy, a therapeutic keratoplasty with intracameral tissue plasminogen activator (tPA) was recommended.
Clinical case continued
The patient underwent therapeutic penetrating keratoplasty with a 9-mm corneal graft. Two peripheral iridotomies were created. The anterior chamber was washed with balanced salt solution, 25 µg/0.1 mg tPA was injected intracamerally, and subconjunctival injections of cefazolin and gentamicin were given. The host cornea was sent for culture and pathology. After surgery, the patient was started on moxifloxacin and 0.5% cyclosporine drops four times a day.
Because the culture grew Fusarium solani, the decision was made to start topical antifungals. The patient was started on topical amphotericin as he was unable to obtain natamycin eye drops. At postoperative day 5, the pain resolved, visual acuity was hand motion, and IOP was 24 mm Hg on timolol twice daily with 50% epithelial defect; there were a few small corneal infiltrates near the sutures, no hypopyon, 2+ anterior chamber cells and a 1-mm layered hyphema (Figure 4). At postoperative 6 weeks, vision improved to count fingers at 3 feet, and IOP was 14 mm Hg off drops. The corneal graft remained clear without epithelial defect. The corneal infiltrates, anterior chamber reaction and hyphema resolved without complications.
Discussion
In the United States, fungal keratitis constitutes up to 20% of microbial keratitis. Risk factors include trauma with soil or plant matter, contact lens wear, ocular surface diseases, immunosuppression, topical medications such as corticosteroids, anesthetics and antibiotics, and previous corneal surgery. The clinical presentation can be insidious and often overlaps between symptoms and signs of bacterial infection, leading to delayed diagnosis and treatment. Thus, corneal culture is indicated for all suspected cases. Patients who are not responding to antibiotic therapy, specifically on fortified drops, should raise suspicion for fungal keratitis. Often, re-culture is warranted, and if negative, a corneal biopsy or corneal suture biopsy can aid in diagnosis in highly suspicious cases. In our patient, there was a delay in seeking medical care in conjunction with a demographic barrier from where he lived to the nearest cornea specialist for frequent follow-up. Hence, when he was seen at our department, the disease was advanced and quickly progressed, requiring a therapeutic keratoplasty.
IVCM can be a sensitive diagnostic tool for filamentous keratitis in which one can appreciate hyphae on imaging and their depth. It is particularly useful in differentiating from Acanthamoeba or in cases in which the organism cannot be cultured. In a large retrospective study, Hoffman and colleagues demonstrated that IVCM was the most sensitive test to diagnose fungal and Acanthamoeba keratitis (81.8% and 77.1%, respectively) compared with PCR and culture. We hypothesize that our patient’s infection infiltrated deep within the cornea and penetrated to the anterior chamber, limiting the imaging resolution and visualization of the pathogen. This would also explain the patient’s negative fungal culture results, in which tissue is collected from superficial tissue.
Fusarium species are the most common isolated fungi in corneal cultures (42.2%), followed by Aspergillus (32.8%) and Candida (1.3%). In filamentous keratitis, topical natamycin showed improved outcomes compared with topical voriconazole. Amphotericin B also has good coverage for filamentous fungi. There is some evidence that oral voriconazole in addition to topical antifungals for Fusarium infection decreases the chance of complications. However, it did increase the rate of adverse reactions while on these systemic medications. Commonly reported side effects from systemic voriconazole include skin rash, fever, epistaxis, hyperkalemia or hypokalemia, and hepatic toxicity. The patient and his local provider opted to not undergo oral antifungal therapy.
Therapeutic keratoplasty is recommended for managing infectious keratitis unresponsive to conventional treatments, aiming to restore globe integrity or eradicate the infection. Bacterial and fungal infections are the most frequent causes requiring surgical intervention. Therapeutic keratoplasty plays a critical role in reducing the infectious burden in recalcitrant keratitis, with a reported cure rate reaching up to 100%. Postoperative use of corticosteroids is crucial for controlling inflammation and preventing corneal graft rejection. However, in the setting of mycotic keratitis, corticosteroids are avoided to prevent worsening of an underlying infection or causing a superinfection. Instead, topical cyclosporine A 0.5% has proven to be a safe and effective alternative, reducing or eliminating the need for corticosteroids after therapeutic keratoplasty in fungal keratitis.
The presence of hypopyon can lead to an increase in IOP due to obstruction or synechiae of the trabecular meshwork with the fibrotic material in the anterior chamber. Medical therapy is the initial approach. Glaucoma surgery is only indicated if IOP is persistently high on optimal therapy or if there is an underlying diagnosis of advanced glaucoma. The removal of hypopyon with anterior chamber irrigation often resolves the obstruction with improvement of IOP. For our patient, he quickly developed a complete hypopyon with indication for therapeutic keratoplasty. Given the size of the hypopyon, in addition to anterior chamber irrigation, intracameral injection of tPA was performed with complete resolution of hypopyon and IOP improvement postoperatively. Intracameral tPA has been described in multiple case series in patients with anterior chamber inflammation. Hu and colleagues described its use in uveitic eyes undergoing cataract surgery. They noted that the fibrin in the anterior chamber resolved in 47.2% of eyes at postoperative week 1 and 80% of eyes at postoperative month 1. There was also improvement of posterior synechiae at 1 year. Incidence of hyphema and/or vitreous hemorrhage was 16.7%, and the majority of cases (66.7%) resolved spontaneously.
- References:
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- Hoffman JJ, et al. Eye (Lond). 2022;doi:10.1038/s41433-021-01812-7.
- Hu WF, et al. Ocul Immunol Inflamm. 2024;doi:10.1080/09273948.2023.2194410.
- Miller D, et al. Fungal keratitis, In: Mannis MJ, et al, eds. Cornea: Fundamentals, Diagnosis and Management. Elsevier. 5th ed. 2021;880-895.
- Prajna NV, et al. JAMA Ophthalmol. 2013;doi:10.1001/jamaophthalmol.2013.1497.
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- For more information:
- Edited by William W. Binotti, MD, and Julia Ernst, MD, PhD, of New England Eye Center, Tufts University School of Medicine. They can be reached at william.binotti@tuftsmedicine.org and julia.ernst@tuftsmedicine.org.
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