Heba Mahjoub, MD; Susan Tucker, MD; Amal Alwreikat, MD; Sarkis H. Soukiasian, MD , 2025-05-05 14:52:00
A 75-year-old man was referred by an international ophthalmologist for progressive corneal ulceration and possible endophthalmitis of the right eye.
The patient’s medical history was notable for appendiceal cancer s/p colostomy, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy, splenectomy, retroperitoneal sarcoma, hypertension and hypercholesterolemia. He never had ocular surgery and was not a contact lens wearer. His only allergy was to adhesive materials. Family history was noncontributory. He was a former smoker with a 4.7 pack-year history spanning from 1967-1971. He drank one alcoholic drink per month, with no notable drug use history.
Images: Heba Mahjoub, MD, Susan Tucker, MD, Amal Alwreikat, MD, and Sarkis Soukiasian, MD
The patient was referred to our team 1 month after the initial onset of his symptoms, which included ocular pain and light sensitivity. The history of presenting illness was complex and limited. According to the notes sent with the patient from his international ophthalmologist, he was initially found to have a hypopyon and was presumed to have a diagnosis of uveitis. He was started on prednisolone acetate eye drops for presumptive iritis with initial improvement, but the pain recurred and persisted. Another ophthalmologist noted corneal ulceration, so fortified antibiotics including vancomycin and a cephalosporin were added, as well as oral voriconazole and a short course of oral prednisone for significant inflammation. Cyanoacrylate adhesive was applied due to progression, and the patient was then referred to our team.
Examination
On our initial examination, the patient had a shield and gauze covering the right eye, and when they were removed, the crystalline lens was adherent to the gauze (Figure 1). Best corrected visual acuity was hand motion only in the right eye and 20/20-1 in the left eye. IOP was unobtainable in the right eye and 14 mm Hg in the left eye. Pupil exam in the right eye was not possible, but the left eye pupil was within normal limits. Confrontational visual fields and extraocular motility were normal in the left eye but not the right eye. In the right eye, anterior segment exam revealed dense crusting on the eyelid margin, 2+ conjunctival injection and diffuse dense gelatinous material attached to the cornea with diffuse dense infiltrate (Figure 2). There was prolapsed iris and vitreous material centrally. The anterior chamber could not be appreciated. Anterior segment exam of the left eye revealed nasal pinguecula, shallow anterior chamber and mild cataract. Dilated exam of the left eye was unremarkable. Bacterial cultures, fungal cultures and viral molecular testing for herpes were sent.
What is your diagnosis?
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Corneal ulcer
The differential diagnosis for this patient’s presentation with corneal ulcer and hypopyon includes primary infection and possibly inflammatory causes.
Infectious causes must be considered primarily and promptly evaluated, as they can progress rapidly, causing significant morbidity. These may include severe bacterial keratitis with perforation and secondary endophthalmitis, fungal keratitis with endophthalmitis, and viral keratitis with possible necrotizing secondary bacterial or fungal endophthalmitis. Less likely causes may include systemic infections such as tuberculosis or syphilis. A hypopyon may be a presenting feature of endogenous endophthalmitis, but this patient had no occult infections or risk factors for endophthalmitis, and a secondary keratitis and perforation would be unusual.
Inflammatory diseases presenting with anterior uveitis and hypopyon may include HLA-B27-associated anterior uveitis or possibly Behçet’s disease, but a secondary keratitis or corneal ulceration would be unusual.
It should be noted that the typical presentation and progression of infectious causes may be affected by the concurrent use of corticosteroids. In our patient’s case, infection was highly suspected, and the differential diagnosis was ultimately narrowed by the growth of the fungus Fusarium on cultures performed in clinic at initial presentation. Upon growth of Fusarium, further history was gathered from the patient, revealing exposure to soil while gardening at the time of possible initial injury.
Discussion
Infectious keratitis is common but can be devastating if left undertreated, as in this case where it spread beyond the cornea. Fungal infections are less common than bacterial and are often underdiagnosed as they can be mistaken for a bacterial or viral infection. They are more insidious initially, in contrast to bacterial infections, which can be rapidly progressive and destructive. However, steroids can alter the natural course. Fusarium was found to be the second most common cause of fungal keratitis (Bograd et al.). Fusarium species, a group of filamentous fungi, are more common in regions that are tropical and subtropical, which is where this patient resided (Ortega-Rosales et al.). Yeast such as Candida species are more common in our region of the Northeast United States. Initial symptoms often include light sensitivity, pain, excess tearing and vision loss. Although typically slowly progressive, with the concurrent use of corticosteroids, fungal infections can progress rapidly and aggressively and can invade other structures of the eye. Cultures for both fungi and bacteria should be done as they may be difficult to differentiate.
Treatment is dependent on prompt diagnosis and follows the topical, systemic and targeted therapy (TST) protocol. This includes initial treatment with topical 5% natamycin, along with oral ketoconazole or voriconazole in ulcers larger than 5 mm with depth greater than 50%. If there is poor response at 7 to 10 days, topical 1% voriconazole may be added. Other studies have shown that therapy with oral fluconazole or ketoconazole and topical natamycin is inadequate in severe Fusarium keratitis with intraocular spread (Dursun et al.). Therefore, the TST protocol encourages intracameral antifungals and penetrating keratoplasties if patients remain unresponsive to other treatments (Sharma et al.).
Some fungal infections continue to progress despite prompt and appropriate treatment. A case report by Maberry and Kesterson described the quick progression of infection that led to lens expulsion secondary to Fusarium endophthalmitis. In their case, the patient required two penetrating keratoplasty procedures as well as intravitreal voriconazole before controlling the infection. In one retrospective study of 791 cases of endophthalmitis necessitating evisceration, 58% were found to be due to post-microbial keratitis, of which 42% were due to Aspergillus (Dave et al.). Lu and colleagues found that several factors were strongly associated with evisceration or enucleation, including corneal ulcer, endogenous endophthalmitis, being a woman, older age, poor initial visual acuity and delayed intervention. Surprisingly, rates of sympathetic ophthalmia are rare in cases of extensive endophthalmitis, especially for eyes that receive multiple intravitreal antibiotics and periocular dexamethasone (Chen et al.).
Clinical course
At the time of our initial examination of the patient, his symptoms had already been ongoing for at least 1 month, if not longer. He was immediately treated within 3 hours of arrival with urgent tectonic corneoscleral graft placement, along with intravenous vancomycin and cefepime before surgery. After surgery, he was started on moxifloxacin every hour while awake, fortified tobramycin three times a day, 400 mg of oral moxifloxacin daily, cyclopentolate twice a day, prednisolone three times a day, oral voriconazole and a rapid oral prednisone taper. Our cultures confirmed a deep, advanced fungal infection of the cornea that ultimately led to corneal melting and complete perforation with crystalline lens extrusion and prolapsed iris and vitreous. Despite these treatments, his hypopyon persisted (Figure 3). A B-scan ultrasound revealed no retinal detachment and no obvious mass in the eye (Figure 4). The decision was made to inject voriconazole into the anterior chamber for infection control. However, at the next postoperative visit on day 7, the patient’s hypopyon continued to enlarge (Figure 5) and vision remained poor at hand motion only. Another voriconazole injection was given into the anterior chamber. Follow-up on day 11 (Figure 6) showed continued worsening despite maximum medical, topical and intraocular injections with antifungals. At that time, the decision was made to divert to evisceration with silicone implant to prevent pain and further spread of the infection. The patient is healing well at this time and will be fit with a prosthesis when appropriate.
- References:
- Bograd A, et al. Klin Monbl Augenheilkd. 2019;doi:10.1055/a-0774-7756.
- Chen KJ, et al. PLoS One. 2017;doi:10.1371/journal.pone.0169603.
- Dave TV, et al. J Ophthalmic Inflamm Infect. 2019;doi:10.1186/s12348-019-0174-y.
- Dursun D, et al. Cornea. 2003;doi:10.1097/00003226-200305000-00004.
- Lu X, et al. Sci Rep. 2016;doi:10.1038/srep28100.
- Maberry M, et al. J Emerg Med. 2022;doi:10.1016/j.jemermed.2021.09.022.
- Ortega-Rosales A, et al. IDCases. 2019;doi:10.1016/j.idcr.2019.e00618.
- Sharma N, et al. Cornea. 2019;doi:10.1097/ICO.0000000000001781.
- 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.
