When a patient presents with a corneal ulcer, you know you need to act quickly to preserve your patient’s vision. While most infectious corneal ulcers are bacterial in origin, distinguishing between bacterial, fungal, viral, and protozoan infections is crucial to treat patients promptly when their sight is on the line.
This article will discuss the diagnosis and management of various infectious corneal ulcers. This article can help you distinguish noninfectious ulcers such as those caused by neurotrophic keratitis.
In a primary care setting, the most common type of infectious ulcer and is caused by bacteria. These happen most in our patients who are contact lens wearers, those with ocular surface disease, or after ocular surgery or trauma. Patients will present with a painful red eye, with purulent discharge, foreign body sensation, and possibly decreased visual acuity depending on location. Severe cases may have an anterior chamber reaction.
Most bacterial ulcers are caused by gram-positive bacteria and typically respond to topical broad-spectrum fourth-generation fluoroquinolones. Ulcers caused by the gram-negative bacteria (e.g., Pseudomonas) have less defined edges and significant discharge. Other classic signs of Pseudomonasmonasomonas include severe anterior chamber reaction, greater infiltrate size, and more rapid progression.
Bacterial keratitis treatment
Bacteria replicate quickly, so treatment needs to be aggressive and frequent. After culturing, if indicated (see below), begin topical fourth-generation fluoroquinolone every 5 minutes for the first half-hour (begin this while the patient is in the office), then have the patient use hourly even through the night.
If the ulcer is larger than 2mm, consider adding a fortified antibiotic. If this isn’t feasible, prescribe tobramycin in addition to the fluoroquinolone hourly, each drop separated by 30 minutes. This will provide even more broad-spectrum coverage. After 24 hours, the patient can reduce the overnight schedule to every 2 hours, with both drops separated by 5 minutes.
Keep in mind the increasing resistance of MRSA and Pseudomonas to topical fluoroquinolones. Be wary of this, especially if your patient is in a hospital or nursing home, works in a medical environment, or has previously been on antibiotics without success.
After culturing and starting antibiotic therapy, the patient should improve within 24 hours. The epithelium should begin closing in the subsequent days, the ulcer getting smaller and the eye generally looking better. Vision will be the last to improve. If you don’t have signs of some improvement within 4-7 days, this is atypical of a bacterial ulcer, and the patient should see a corneal specialist.
Ulcers that are large or near the visual axis need to be followed daily until signs of improvement are evident.
Herpes simplex keratitis presents with classic dendritic epithelial lesions. Be careful, however, as the early presentation may not yet have fully developed dendrites. Pay attention to whether the patient has a prior history of similar episodes. The patient will experience photophobia; however, they will not feel as much pain as you would expect by looking at their eye due to reduced corneal nerve sensitivity. The cotton wisp test can help test for this.
Viral keratitis treatment
Viral epithelial keratitis is treated with topical Viroptic 9 times per day or oral acyclovir 400mg five times per day for 7 to 10 days. Topical meds should be continued 9x/day for 7-14 days until epithelium is healed and then four times per day for four days then stop.
Follow patients every 2 to 7 days to check the response to treatment, then every 1 to 2 weeks monitoring the size of the epithelial defect and ulcer, corneal thickness, depth of corneal involvement, anterior chamber reaction, and IOP. Topical steroids are used for treating stromal disease and need to be tapered.
If epithelial defects suspected of being herpetic in origin have not resolved within 1-2 weeks, suspect either noncompliance, topical antiviral toxicity, or Acanthamoeba keratitis. Topical antivirals should be stopped, and the patient started on preservative-free artificial tears and smears for Acanthamoeba performed.
Be wary of fungal keratitis in any case of ocular trauma from vegetative matter. Classically these lesions will present as grayish with feathery edges with branches to the lesion. However, when these cases have persisted for a while before presentation to your office, they may appear similar to bacterial ulcers. While the patient may still present with foreign body sensation and photophobia, they typically don’t have mucus discharge because there is not as much tissue damage as in bacterial ulcers.
Fungal keratitis treatment
Natamycin is the only commercially available anti-fungal. Treatment hourly during the day is initially recommended. These patients will need, on average, about six weeks of treatment. The fungus does not replicate as quickly as bacteria do, so dosing does not need to be as aggressive as with bacterial infections overnight.
Monitor closely for signs of penetration into deeper ocular tissues in these cases. Medication may need to be injected directly into the stroma, or the patient may need an urgent corneal transplant to prevent the infection from spreading into the rest of the eye.
Be suspicious of Acanthamoeba keratitis in contact lens wearers, especially if they have a history of swimming in a lake or using tap water to clean their contacts. This large study found that acanthamoeba keratitis could be distinguished clinically from bacterial or fungal infections as it was more likely confined to the corneal epithelium and had the presence of a ring infiltrate. Acanthamoeba keratitis may most closely resemble herpetic keratitis clinically due to the irregular epithelial margins and perineural infiltrates.
The main differentiating factor clinically will be with Acanthamoeba; the patient will be in extreme pain and very light sensitive versus herpetic keratitis where the patient will also be extremely light-sensitive but in much less pain than you would anticipate by looking at the cornea.
Parasitic keratitis treatment
Acanthamoeba is challenging to treat. In 2019, the FDA approved the first topical treatment for acanthamoeba keratitis, miltefosine. However, despite treatment lasting months, these patients often require a corneal transplant to save the vision and prevent the infection from spreading into deeper tissues within the eye. For more information on acanthamoeba keratitis and for more resources to manage these patients, visit this website by AK patient advocate.
Clinical signs to differentiate infectious microbial keratitis
|Corneal signs||round ulcer||satellite lesions||herpes simplex keratitis shows classic dendritic pattern||satellite lesions|
|large epithelial defect overlying ulcer||feathery/irregular margins with branching borders||If early in disease, may not show full dendrite yet||ring infiltrates|
|mucus discharge||dry, raised, necrotic infiltrates||-------||-------|
|-------||colored infiltrates (not yellow)||-------||-------|
|-------||will NOT have significant discharge||-------||-------|
|Classic symptom||Foreign body sensation with blinking, pain, mucus discharge||Longer history of symptoms; suspect if trauma w/ vegetative material||Pain < clinical signs; severe photophobia||Pain > clinical signs; severe photophobia|
When to culture
Of course, we’re all most concerned about sight-threatening lesions or those that don’t respond to our initial treatment. Keep in mind that once treatment has been initiated, culturing may not be as reliable.
According to the American Academy of Ophthalmology Preferred Practice Patterns, an ulcer should be cultured when:
- Corneal infiltrate is central, large (>2mm), or with significant stromal involvement/melting.
- It is chronic or non-responsive to broad-spectrum antibiotic.
- There is a history of corneal surgery.
- Atypical features indicative of fungal, mycobacterial, or amoeba keratitis are present.
- There are multiple infiltrates throughout the cornea
Once you determine when to culture, you’ll need to know-how. Check out this article for tips on everything you need to know for culturing.
Other considerations for patient comfort and improved healing
Two therapies that should not be overlooked are cycloplegia and corticosteroid use. Cyloplegia is indicated where there is a significant anterior chamber reaction to limit synechia formation and reduce pain.
Topical steroids can be added after 24-48 hours in cases of bacterial keratitis to improve patient comfort only once the causative agent has been identified or the cornea has started to show signs of improvement (such as the epithelial defect starting to close). Steroids should be avoided when the ulcer is caused by Acanthamoeba, Nocardia, or fungus as well as with the Herpes virus.
Further treatment options
A therapeutic corneal transplant may be indicated in very severe cases where a visually significant ulcer is not healing. This may also be considered if there is substantial peripheral blood vessel growth. Be careful in cases of immunocompromised patients or those with rheumatologic disease who may be poor healers. These patients would not be good candidates for a corneal transplant.
Infectious corneal ulcers require you to act quickly to save your patient’s sight. Differentiating between bacterial, fungal, viral, and parasitic is crucial for determining the proper treatment.
Check out the cheat sheet for a quick guide you can follow in the clinic to guide your diagnosis and treatment plans.
Next time a patient comes in with a corneal ulcer, you’ll be ready to take quick action towards getting them better.