Man presents with 2 weeks of blurry vision, dryness, redness in left eye
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A 30-year-old man presented with chief complaints of blurry vision, dryness and redness in the left eye for 2 weeks. He was previously started on a lubricating ointment and Tobradex drops with some improvement but not complete resolution.
He had an ocular history of myopia and astigmatism. He was a rigid gas permeable contact lens wearer and washed his lens in tap water before insertion. He had a history of cold sores with no ocular involvement. He denied prior ocular trauma or recent travel and took no medications.
Source: Julia Ernst, MD, PhD, and Helen K. Wu, MD
Examination
On exam, uncorrected distance visual acuity was 20/20 in the right eye and 20/80 in the left eye. Pupils were equal, round and briskly reactive to light bilaterally with no relative afferent pupillary defect. IOPs were normal. Extraocular motility and confrontation visual fields were full bilaterally.
Slit lamp exam revealed trace punctate epithelial erosions and marked superior limbal neovascularization in the right eye. In the left eye, the conjunctiva was injected, and the cornea was irregular, with a whorled epithelium centrally and trace haze measuring 3.5 mm × 5.25 mm. Significant superior neovascularization was present. The anterior chamber in both eyes was deep and quiet. The iris had no rubeosis or atrophy, and the lens was clear bilaterally. The posterior segment exam of both eyes was unremarkable.
Imaging
On the initial visit, color slit lamp photos (Figure 1) and confocal microscopy images (Figure 2) were taken. In the left eye, the conjunctiva was injected, and the cornea was irregular with significant neovascularization present superiorly (Figure 1a). Figure 1b demonstrates whorled epithelium centrally with trace haze. Confocal microscopy images revealed significant disorganization and infiltration of corneal epithelium with inflammatory cells (Figure 2).
What is your diagnosis?
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Blurry vision, conjunctival injection
The patient’s symptoms of blurry vision and signs of conjunctival injection and an irregular cornea with whorled epithelium and central haze are strongly suggestive of an infectious origin. Given the patient’s contact lens wear with poor hygiene and continuing symptoms despite treatment, Acanthamoeba keratitis (AK) was high on the differential. Also, based on presentation, other infectious etiologies should be considered, including bacterial and herpes simplex virus (HSV) keratitis.
AK is usually unilateral and progresses slowly. Symptoms can range from discomfort to ocular pain disproportionate to clinical signs. Symptoms also commonly include conjunctival hyperemia, ptosis, blurred vision, excessive tearing and blepharospasm. Infection starts superficially in the epithelium and then involves the stroma. Typical findings are pseudodendritiformic epitheliopathy, epithelial microerosions, microcysts and multifocal stromal infiltrates. Pathognomonic signs are ring infiltrate and peripheral perineural infiltrates, which usually occur later in the course of the infection.
In the early stages, AK can be confused with HSV keratitis due to a pseudodendritiformic appearance with gray epithelial opacities, often resembling dendritic or geographic HSV keratitis. However, in AK, the epithelial defects lack terminal bulbs.
In the advanced stages, AK can resemble bacterial or fungal keratitis. What differentiates AK from these infections are multifocal, dot-like, partly transparent infiltrates. Mycotic or bacterial stromal infiltrates are typically monofocal and thicker; however, satellite infiltrates in mycotic keratitis can occasionally resemble AK infiltrates. Corneal ring infiltrates, which may also occur in bacterial and fungal infections, can confound the clinical diagnosis. However, the above-mentioned differences in appearance of infiltrates and more common epithelial defects in AK should aid in identifying the correct diagnosis. Furthermore, the presence of perineural stromal infiltrates is strongly suggestive of AK.
Workup and management
The patient had developed left eye dryness and redness associated with decreased vision 2 weeks prior to his initial visit to the New England Eye Center. He had been started on lubricating ointment and Tobradex (tobramycin/dexamethasone, Santen) drops. On presentation to our clinic, he underwent superficial keratectomy with corneal culture and confocal imaging. Based on clinical presentation, imaging results and his history of contact lens wear with poor lens hygiene, the patient was diagnosed with AK.
The Tobradex drops were discontinued, and he was started on polyhexamethylene biguanide (PHMB) every 1 hour around the clock in the left eye. A bandage contact lens was placed after superficial keratectomy, so he was started on moxifloxacin four times a day in the left eye for 1 week. Initially, he was seen every 2 to 4 days. His signs and symptoms started to improve after a week of therapy with visual acuity improvement from 20/80 to 20/50 in the left eye. He continued to take PHMB every 1 hour while awake, but it was decreased to every 3 hours overnight for another 5 weeks. At 6 weeks, his pinhole visual acuity reached 20/40, and central corneal opacity remained stable and resembled a scar. The PHMB regimen was decreased to every 2 hours while awake and every 3 hours at night. Color slit lamp photo of the left eye (Figure 3) after 8 weeks of therapy showed a quiet conjunctiva, and the central corneal opacity appeared more like a corneal scar, confluent centrally and decreased in size compared with initial exam findings. Superior neovascular corneal vessels were less engorged.
The patient underwent a slow taper of PHMB over 10 months with reduction of PHMB at 3 months to every 3 hours, at 4 months to every 4 hours, at 6 months to three times a day and at 9 months to twice a day, until it was finally stopped 10 months after diagnosis. At 4 months after initiation of therapy, confocal microscopy images demonstrated decreased inflammation and normal epithelial morphology. However, it continued to show abundant dendritic cells, suggesting ongoing inflammation (Figure 4a). It also revealed irregular nerves with microneuroma formation (Figure 4b). The patient now has patchy central stromal haze and visual acuity of 20/30.
Discussion
AK is a sight-threatening eye infection that is caused by an opportunistic unicellular protozoan Acanthamoeba. It is a rare disease with a prevalence of about one to nine in 100,000. Acanthamoeba is ubiquitous in nature, and therefore, people come in frequent contact with this organism. It can be found not only in typical fresh or salt water environments, hot tubs or swimming pools, to name a few, but also in air, soil, vegetation, animals, and even on surgical instruments or in sterile saline solutions. Human infection is most likely to occur through contact lenses or trauma with infected material.
Acanthamoeba exists in two distinct forms: an active trophozoite and a dormant cystic stage. Trophozoites are capable of replication, movement, growth and feeding through acanthopodia, which are protoplasmic projections. When they come into contact with the damaged surface of a cornea either through contact lenses or other trauma, they can adhere, penetrate and cause infection. They feed on keratocytes. Based on the Acanthamoeba genotype, trophozoite size varies from 15 µm to 50 µm. The dormant cystic stage is composed of double-walled cysts, which are inactive and form under unfavorable conditions including but not restricted to extreme temperatures, desiccation and presence of chemicals. They can survive for decades while retaining their infectious potential. Hence, they can cause persistent infections. Their size also varies from 5 µm to 30 µm depending on genotype. There are 22 genotypes (T1 to T22) discovered to date with the most common infectious species being Acanthamoeba castellanii and Acanthamoeba polyphaga, both from the T4 genotype, which is also the most virulent one.
The greatest risk factor for AK is the use of contact lenses. It is reported that up to 85% of AK happens in contact lens wearers. Because it is rare, it is often misdiagnosed in up to 75% to 90% of cases. For clinicians, it is important to gather appropriate history with a particular focus on contact lens hygiene. Typically, suspicion is raised in patients who have a history of overnight wear or who use tap water when handling or storing their lenses. Diagnosis based on initial presentation is difficult because signs and symptoms resemble other corneal infections. However, AK should be suspected in individuals with corneal infiltrates linked with inflamed nerves, chronic keratitis associated with a ring infiltrate, or suspected HSV or bacterial keratitis refractory to anti-HSV or antibacterial therapy, respectively.
The standard diagnosis of AK consists of corneal culture, polymerase chain reaction (PCR), histopathology (from corneal scraping or biopsy) or in vivo confocal microscopy (IVCM). The relative sensitivity is high, reaching 90%, for IVCM, provided it is assessed by an experienced examiner. Other benefits are the ability to detect mixed keratitis and rapid results, which is invaluable for AK management. The sensitivities for corneal culture, PCR and histopathology are 0% to 77%, 84% to 100% and 31% to 65%, respectively. For prompt diagnosis of AK, clinical suspicion is essential to avoid adverse patient outcomes.
There are no randomized controlled clinical studies to guide treatment of AK. In general, AK is treated with eye drops containing a biguanide such as PHMB and chlorhexidine with or without diamidine, such as propamidine isethionate, hexamidine diisethionate and dibromopropamidine. These agents are effective in eradicating Acanthamoeba cysts, which are the causative form for persistent infections. Additional agents that can be used are antibiotics such as neomycin that are thought to decrease potential food sources for Acanthamoeba and prevent superinfection. Use of steroids is controversial. While corticosteroids can decrease inflammation, and hence patient discomfort, they can lead to suppression of the native immune response. When used at the early stage of AK, corticosteroids are linked to worse patient outcomes. Treatment initially involves frequent application of eye drops. Patients are closely monitored to assess response to therapy and need for management modifications. Treatment is continued for several months with slow taper of the eye drops. Unfortunately, 25% of AK patients progress despite medical treatment and eventually require corneal transplantation. In cases of successful treatment, patients can have complications such as cataract formation, iris atrophy, scleritis or secondary glaucoma.
In summary, treatment outcomes are usually favorable, provided AK is diagnosed early and definitive treatment is initiated rapidly. Prevention involves contact lens wearer education about lens hygiene and avoidance of common risk factors. Most important for diagnosis of AK, however, is early consideration of this rare condition.
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- For more information:
- Edited by Yi Ling Dai, MD, and Teresa P. Horan, MD, of New England Eye Center, Tufts University School of Medicine. They can be reached at ydai@tuftsmedicalcenter.org and thoran@tuftsmedicalcenter.org.