Updates on Ocular Surface Disease, Glaucoma, and Cataract Comanagement

he overwhelming majority of keratitis visits to eye care practitioners (76.5%) result in antimicrobial prescriptions.¹Worldwide, bacterial infections are still predominant and are found in 80% of patients with ulcerative keratitis.² In the United States, about 30,000 cases of infectious keratitis are reported yearly.³ Worldwide, there are approximately 1.5 million cases yearly.⁴ That makes infectious keratitis one of the leading causes of corneal blindness worldwide. The at-risk population includes contact lens wearers, with overnight contact lens use the leading risk factor; this group comprise a much higher risk factor than the average patient.⁵

Second, people with comorbid ocular surface pathology, including dry eye, are also at risk. The third leading risk factor is ocular injury/trauma that can be surgical, from a fingernail, or a foreign body.^6,7

Other at-risk populations include immunocompromised individuals, those who frequently use ocular medications, and those with poor lid mechanics/exposure.⁶

During the examination, being as detailed as possible with a case history is necessary to help determine when the infection began, and may identify clues to help determine what kind of bacteria may be causing the infection. When possible, document as specifically as possible (within 1/10th of a millimeter) the size of the epi-defect, whether there is any excavation present, detailing the size of the infiltrate and its appearance, its density, and include a description of satellite lesions, if present.

Incorporating culturing into a primary OD practice is becoming more common. We recommend culturing when the defect is central, had a rapid onset (within 24-48 hours of presentation), is large (>3mm), or is nonresponsive to initial treatment. See Figure 1 for a decision tree algorithm.⁸

Figure 1. When to culture.

HOW TO CULTURE

The standard method for culturing involves scraping the lesion either with a swab or a spatula; our preference is calcium alginate swabs, which have a fairly small tip as opposed to a standard cotton swab. In our hands, we can use those swabs to dig into the lesion, enabling us to potentially get a higher rate of bacterial accumulation at the end of the tip so plating is more likely to be successful.

Traditional culturing includes using a variety of medium— the primary medium used for aerobic bacteria are blood and chocolate plates, and thioglycate broth. Other media can be used to look for anaerobic bacteria, atypical mycobacteria, fungus or yeast, and even virus.

There has been an increasing trend toward the use of e-swabs. This has simplified the process for practitioners in that we can now culture several types of bacteria with a single medium. They overcome several disadvantages of plating, including

being able to be stored at room temperature for short periods of time, avoiding the condensation plates develop from being stored upside down, and being less sensitive to temperature fluctuations. However, they are also unable to capture several classes of bacteria, including atypical mycobacteria.

BACTERIAL IDENTIFICATION

There are two primary types of bacteria that we encounter most frequently—Gram-positive and Gram-negative. Gram-positive organisms account for 50% to 90% of all keratitis cases seen in the United States.^9-11 Staphylococcus is the most frequently isolated organism from bacterial keratitis.⁸ Insurance data showed the most common cause of bacterial keratitis is S. aureus.12 S. aureus are typically round lesions, with more focal infiltrates with distinct edges. Methicillin-resistant S. aureus (MRSA) is the most common post-LASIK infection in the United States.¹³ MRSA has been found responsible for 52.8% of keratitis infections in one Taiwanese hospital.¹⁴

In Figure 2, the overlying epi-defect is typically just a little bit less than the size of the infiltrate. These tend to worsen over the course of about 2 or maybe 3 days.

Figure 2. Examples of Staphylococcus aureus.

Conversely, Streptococcus pneumoniae is a much more aggressive organism that tends to evolve at a faster pace. Like Staph infections, Strep infections typically are very dense, with very focal white infiltrates, but which may become severe within 1 or 2 days from onset. It is difficult to see much in the iris detail through the lesion. S. pneumoniae occurs deeper and tends to also be associated with a higher likelihood of anterior chamber reaction. As Figure 3 illustrates, it is not unusual for hypopeon to be present in patients with Strep infections.

Figure 3. Examples of Streptococcus pneumoniae.

Several classes of drugs are available to treat Gram-positive infections, including macrolides, fluoroquinolones, and glycopeptides. These days, we tend to prescribe chlorinated fluoroquinolones, such as besifloxacin, which has demonstrated good efficacy against Gram-positive organisms, including MRSA.¹⁵The fourth-generation fluoroquinolones remain a viable and trusted option. Besifloxacin is commercially available and highly recommended because it does not need to be compounded.¹⁶ Polytrim and tobramycin are also used, but tobramycin is the least effective of these options.

MRSA outbreaks are increasing in all presentations, so whether you are treating a conjunctivitis, cellulitis, or keratitis, keep the possibility of MRSA in mind.

Trust in the Rule of 1-2-3: For any lesion that is within 1 mm of the visual axis, if the eye has 2 or more lesions, or if the lesion is 3 mm in size or larger, the use of fortified antibiotics or prescribing two different antibiotics is recommended.

The Ocular Trust 3 and ARMOR studies^17-19 showed us that many antimicrobials work on typical non-MRSA Staph infections. However, those same studies showed that fewer than one-third of fluoroquinolones work against MRSA, with the exception of trimethoprim and tobramycin.^17-19 The susceptibility profiles remain virtually identical for the fluoroquinolones, regardless of methicillin phenotype. S. aureus is more susceptible to the fluoroquinolones than to macrolides.

For suspected ocular MRSA infection, vancomycin still remains the standard treatment, although it will need to be compounded for use in ocular formulation. If there is a strong suspicion of MRSA, or if the patient has been minimally responsive to general fluroquinolone therapy, then we typically will prescribe vancomycin.

Gram-negative infections are distinct, and account for 10% to 50% of keratitis in the United States.^10,20 The most common of these infections is Pseudomonas aeruginosa: in a study of 1,317 patients with culture-confirmed conjunctivitis, 0.7% were P. aeruginosa.¹⁶ The characteristics of Gram-negative infections include a very rapid onset and progression, and may affect the majority of the cornea within a day of initial onset; there can be marked purulence; a necrosed appearance to epithelium; a deep stromal infiltrate, which may progress to a ring; grayish appearance; and a marked anterior chamber reaction or hypopeon.

These infections are more difficult to treat, and may even perforate within 24 to 36 hours of onset.²¹The faster the infection can be recognized and classified, the better the potential outcome for the patient.

There are two main classes of medications used to treat Gram-negative infections: aminoglycosides and fluoroquinolones. We primarily use fortified tobramycin (compounded). Besifloxacin has also demonstrated efficacy against Pseudomonas.16 Oral doxycycline and tetracycline can be useful in more aggressive, necrotic ulcers and are typically adjunctive therapies.21 Animal studies suggest they help speed re-epithelialization through matrix metalloproteinase 9 inhibition and may protect the stroma against necrosis by inhibiting collagenase activity.

The SCUT study²² helped define when steroids are appropriate: results showed that adjunctive topical steroids did not improve 3-month vision in patients with bacterial corneal ulcers. However, topical steroid treatment did improve visual acuity in patients with the worst visual acuity and central ulcer location at baseline. Individualized treatment is necessary, and clinicians need to weigh the risk-to-benefit of adding steroids into their treatment. Generally speaking, steroids are generally not recommended for infectious bacterial corneal ulcers until clinical improvement is noticed with antibiotics alone.

AMNIOTIC MEMBRANE AND CROSSLINKING

Amniotic membrane can help with re-epithelialization and sequestration of white blood cells, which reduces inflammation and scarring,²³ but there are only a few small studies in the literature that analyze amniotic membrane in infectious keratitis. Sheha et al reported on a small case series (n=3), in which amniotic membrane seemed efficacious.²³ This technology may be considered in lieu of a steroid.

Corneal collagen crosslinking for bacterial keratitis may be helpful as well. These cases typically use the epithelium-off method. A patient who presented with a painful peripheral corneal infiltrate underwent PACK-crosslinking with a local limited abrasion and accelerated ultraviolet-A irradiation at 365 mum and 9 mW/cm2 for 10 minutes; PACK-crosslinking was successfully used as a first-line and sole treatment.²⁴ A meta-analysis of outcomes found an 85.8% success rate against bacterial infections and a 78% success rate against fungal infections.²⁵

CONCLUSION

It is important to recognize that both contact lens wearers and people with dry eye are at a higher risk for bacterial infections, and these are likely a majority of the patients in our practices. As a first-line treatment, chlorinated fluoroquinolones are our primary choice when it comes to treating corneal infections. Optometric practices can now incorporate corneal culturing—which may be achieved more easily with e-swabs— that can lead to more rapid identification of the organism and treatment more suited to that particular infection. Finally, technologies emerging for the treatment and management of keratitis are continually evolving and improving our ability to treat patients more rapidly and safely.

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