Keratitis

In this article:

• Treatment
• Noninfectious keratitis
• Infectious keratitis
• Bacterial keratitis
• Fungal keratitis
• Viral keratitis
• Acanthamoeba keratitis
• Surgery for keratitis complications
• Expected Duration
• What is the prognosis of keratitis?
• What is new in keratitis treatment?
• References

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Treatment

Treatment of keratitis should be always guided by a specialist due to potential of the serious complications. Ophthalmologist will confirm the diagnosis and identify the factors causing the breakage of the protective barrier and organism that caused a problem (if it is present). 

While primary care provider sometimes makes the first assessment of the person with red eye symptoms, specialists should be always consulted if the problem is not responding to the treatment, and not limited to the eye:

• Allergist-Immunologist, 
• Infectious disease specialist, 
• Rheumatologist

Noninfectious keratitis

Patients with keratitis and ulcers related to mechanical irritation or allergy and contact reactions need immediate treatment of the underlying causes.

1.  Trichiatic (inverted) eyelashes, entropion, or distichiasis need early correction of pathology. 
2.  Allergic keratitis is a part of the body systemic reaction to an allergen. Request a consultation with the Allergist to determine a cause of the allergic eye disease. you will be given options of the immunotherapy and allergen avoidance. In addition, all measures to reduce allergen will be helpful. Antihistamine and anti-inflammatory eye drops will help to reduce local symptoms and prevent discomfort.
3. Contact lens keratitis. Treatment includes patient education on contact lens care, switch of the lens if there is a personal hypersensitivity. Lens removal and rest for 3-5 days will confirm the diagnosis (is symptoms disappear) and treat the issue. If there is an infection, it should be further treated as infectious keratitis. Some patients just cannot wear contact lens due to personal high sensitivity of the cornea. In this case vision correction with eyeglasses or LASIK surgery may resolve the problem.
4. Dry eye syndrome. Patients with dry eyes need to be evaluated for other systemic problems (Sjogrens syndrome, rheumatoid arthritis etc) and treated accordingly. A consultation with rheumatologist will be helpful in diagnosis and management

Here is an article describing the novel approach to disinfecting contact lens in prevention of the keratitis:

Enhancement of Contact Lens Disinfection by Combining Disinfectant with Visible Light Irradiation. Int J Environ Res Public Health. 2020 Sep; 17(17): 6422. Published online 2020 Sep 3. doi: 10.3390/ijerph17176422 PMCID: PMC7504152 PMID: 32899295

Katharina Hoenes, Barbara Spellerberg, and Martin Hessling

Multiple use contact lenses have to be disinfected overnight to reduce the risk of infections. However, several studies demonstrated that not only microorganisms are affected by the disinfectants, but also ocular epithelial cells, which come into contact via residuals at reinsertion of the lens. 

Visible light has been demonstrated to achieve an inactivation effect on several bacterial and fungal species. Combinations with other disinfection methods often showed better results compared to separately applied methods. We therefore investigated contact lens disinfection solutions combined with 405 nm irradiation, with the intention to reduce the disinfectant concentration of ReNu Multiplus, OptiFree Express or AOSept while maintaining adequate disinfection results due to combination benefits. 

Pseudomonads, staphylococci and E. coli were studied with disk diffusion assay, colony forming unit (cfu) determination and growth delay. A log reduction of 4.49 was achieved for P. fluorescens in 2 h for 40% ReNu Multiplus combined with an irradiation intensity of 20 mW/cm2 at 405 nm. For AOSept the combination effect was so strong that 5% of AOSept in combination with light exhibited the same result as 100% AOSept alone. 

Combination of disinfectants with visible violet light is therefore considered a promising approach, as a reduction of potentially toxic ingredients can be achieved.

Infectious keratitis

Treatment of infection needs to be started as soon as possible. It ensures resolution of keratitis without visual changes. Surgical intervention is sometimes necessary to prevent perforation of the eye structures. Fortified cefazolin 5% or vancomycin and fluoroquinolones or tobramycin or gentamicin give complete coverage against both gram-positive and gram-negative organisms.

Bacterial keratitis

1. Keratitis caused by methicillin-resistant Staphylococcus aureus (MRSA), topical vancomycin is the drug of choice. Topical linezolid 0.2% can also be used for MRSA.
2. Pseudomonas aeruginosa. The patient is started on topical fluoroquinolones hourly. Treatment is modified once the culture and sensitivity report is available. Oral doxycycline is added to halt the progression of collagenolysis. For resistant strains, topical imipenem-cilastatin (1%) or colistin (0.19%) is being used.
3. Nocardia is a gram-positive, aerobic bacillus with thin beaded filaments exhibiting extensive branching at 90°. Nocardia grows well on conventional culture media, though slower than other organisms. Topical fortified amikacin (2.5%) is the treatment of choice. Pre-treatment with topical steroids worsens the prognosis.
4. Atypical mycobacteria. Topical fortified amikacin (4%) is the treatment of choice. Clarithromycin (2%) is the second line of management. However, fluoroquinolones (ciprofloxacin 0,3%) can also be used. 

Fungal keratitis

• Microsporodial spores stain well with Grams, silver, and 10% potassium hydroxide (KOH) with 0.1% calcofluor white. The keratoconjunctivitis variant has a self-limiting course. Topical lubricants can be added to palliate the foreign body sensation. Epithelial debridement is also a valid option for the early resolution of corneal lesions. 
• The deep stromal variant is unlikely to respond to conservative management with oral albendazole (400 mg twice daily for 3-4 weeks) and topical fumagillin (topical, 70 mcg/ml, 2 drops every 2 h for 4 days and then 2 drops 4-times daily). Therapeutic penetrating keratoplasty is the treatment of choice.
• Topical natamycin (5%) is the drug of choice for filamentous fungal keratitis. Topical voriconazole (1%) is added as an adjunct to natamycin in Aspergillus keratitis, not responding to natamycin alone. Voriconazole is not given as a primary drug for fungal keratitis. Systemic anti-fungal is added for large and deep corneal ulcers. 

Viral keratitis

• Adenovirus. Topical 1% povidone-iodine, in combination with 0.1% dexamethasone, has shown good results. The role of steroids in the early stages is controversial. Topical cyclosporine 2%, when added in the acute stage in combination with topical steroids, resulted in inhibition of subepithelial infiltrates.
• Herpes virus (HSV). Topical antiviral (acyclovir 3%- 5 times a day) is the mainstay of treatment for epithelial disease. For HSV stromal disease and endotheliitis, a topical steroid is the mainstay of treatment. Oral acyclovir (800 mg, 5 times daily for 1 week) is very effective in its treatment in the early stages. The recurrent epithelial erosions should largely be managed with lubricants and prophylactic antibiotics. 
• Neurotrophic ulcers are managed with serum, amniotic membrane transplantation, and tarsorrhaphy. 

Acanthamoeba keratitis

• Polyhexamethylene biguanide (PHMB) (0.02%) and chlorhexidine (0.02%) are commonly used biguanides. Monotherapy with one drug is quite effective. Studies suggest a synergistic effect of biguanide (PHMB and chlorhexidine) and pentamidine. The role of voriconazole and BAK (preservative) is under investigation. The role of the addition of levofloxacin to the anti-protozoal treatment regimen might facilitate treatment in resistant cases. 

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Surgery for keratitis complications

The danger of keratitis is in affecting vision. If the eye inflammation does not respond to the initial treatment, surgical intervention (deep anterior lamellar keratoplasty) is a valid option. For cases with perforation, penetrating keratoplasty is the only option, but with poor prognosis.

Some patients with complications require multiple surgical procedures, like the application of tissue adhesives, amniotic membrane transplantation, patch graft, or penetrating keratoplasty, to maintain the integrity of the globe. This holds for all keratitis reaching a fate of severe corneal thinning or perforation. Therapeutic penetrating keratoplasty is planned for limbus threatening infective keratitis. 

Apart from various diagnostic and treatment modalities discussed above, now nanoparticles and antimicrobial peptides are being devised for sustained and targeted drug delivery. In addition to PCR, genotyping, and confocal microscopy, many other modalities are being worked on.

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Expected Duration

Infection cure is fast due the correctly selected treatment with the expected 7–10-day resolution. It is important to have a close follow-up with an ophthalmologist who will monitor progress of recovery. If the treatment did not bring even partial improvement within 1-3 days, it is important to have a culture of the eye to see if there is a resistant bacteria.

Healing of the eye can take a long time dependent on the factors causing keratitis. Overall corneal ulcers take longer for healing. Bacterial ulcers heal relatively early than fungal corneal ulcers. Acanthamoeba keratitis might take even months for complete remission. 

Adenoviral keratitis is a self-limiting disease that usually resolves with only supportive measures within a week. Meanwhile, herpetic infection will require treatment with a good resolution within 3-7 days.

It is crucial to eliminate factors that cause eye inflammation. For example, if the allergy is addressed and treated, it takes 3-5 days to achieve a good resolution. Change of the contact lens type and discontinuation of the lens wear may cause elimination of the inflammation within a week. But it the contacts are inserted again; the disease may immediately come back and new ulcers may develop.

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What is the prognosis of keratitis?

Corneal scarring is the most common outcome following corneal ulcers. These cases can be managed later with glasses or with optical iridectomy or optical keratoplasty to restore vision.  

Perforated corneal ulcers often tend to have a worse prognosis. The use of prior topical steroids in fungal and Acanthamoeba keratitis worsens the prognosis.

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What is new in keratitis treatment?

Corneal collagen cross-linking (CXL). The ability of CXL to increase the resistance of corneal tissue to enzymatic digestion, as well as for UVA to kill microbes offers great promise for a possible role in the treatment of microbial keratitis. 

Within the literature there now several case series of CXL in eyes with microbial keratitis, including cases of Acanthamoeba and fungal infection, unresponsive to anti-microbial therapy. In the majority of cases progression of the melting process was halted within a few days of treatment and emergency keratoplasty avoided. 

This potential application of CXL is extremely exciting with a recent systemic-review and meta-analysis by Alio et al. suggested that CXL had a favourable effect on blocking corneal melting in 85% of cases. 

CXL may offer great potential in the treatment of microbial keratitis as a primary as well as secondary therapy, especially given the increasing reports of anti-microbial resistance to antibiotics and reports of its usage in veterinary practice are also beginning to emerge.

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References

Keratitis. Singh P, Gupta A, Tripathy K.2021 Aug 10. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan. PMID: 32644440 Free Books & Documents. Review.

Contact lens-related corneal infection: Intrinsic resistance and its compromise. Fleiszig SMJ, Kroken AR, Nieto V, Grosser MR, Wan SJ, Metruccio MME, Evans DJ.Prog Retin Eye Res. 2020 May;76:100804. doi: 10.1016/j.preteyeres.2019.100804. Epub 2019 Nov 20.PMID: 31756497 Free PMC article. Review.

The diagnosis and management of contact lens-related microbial keratitis. Carnt N, Samarawickrama C, White A, Stapleton F.Clin Exp Optom. 2017 Sep;100(5):482-493. doi: 10.1111/cxo.12581. Epub 2017 Aug 16.PMID: 28815736 Free article. Review.

Non-contact lens related Acanthamoeba keratitis. Garg P, Kalra P, Joseph J.Indian J Ophthalmol. 2017 Nov;65(11):1079-1086. doi: 10.4103/ijo.IJO_826_17.PMID: 29133630 Free PMC article. Review.

Corneal collagen cross-linking: a review. O’Brart DP.J Optom. 2014 Jul-Sep;7(3):113-24. doi: 10.1016/j.optom.2013.12.001. Epub 2014 Mar 20.PMID: 25000866 Free PMC article. Review.