Keratitis

# Overview
Keratitis is a condition in which the eye's cornea is inflamed.  Superficial keratitis involves the superficial layers of the cornea. After healing, this form of keratitis does not generally leave a scar.  Deep keratitis involves the deeper layers of the cornea, leaving a scar upon healing that impairs vision if on or near the visual axis.  Keratitis has multiple causes, one of which is an infection of a present or previous herpes simplex virus secondary to an upper respiratory infection, involving cold sores. Symptoms of keratitis include red eyes, sensitivity to light, and uncomfortable eyes.  In the later stages of more severe cases, there can be strong pain, loss of vision, blurry vision, and pus.  Microbial keratitis should be managed as bacterial keratitis until proven otherwise. Steroids are indicated in the management of keratitis to reduce inflammation that may damage the eye.

# Classification
Superficial keratitis involves the superficial layers of the cornea. After healing, this form of keratitis does not generally leave a scar.
Deep keratitis involves deeper layers of the cornea, leaving a scar upon healing that impairs vision if on or near the visual axis.

# Pathophysiology
Keratitis has multiple causes, one of which is an infection of a present or previous herpes simplex virus secondary to an upper respiratory infection, involving cold sores.

## Pathogens
- Amoebic keratitis. Amoebic infection of the cornea is the most serious corneal infection, usually affecting soft contact lens wearers. It is usually caused by Acanthamoeba. On May 25, 2007, the CDC issued a health advisory due to increased risk of Acanthamoeba keratitis (AK)infection associated with use of Advanced Medical Optics (AMO) Complete Moisture Plus Multi-Purpose eye solution.  See CDC Advisory
- Bacterial keratitis. Bacterial infection of the cornea can follow from an injury or from wearing contact lenses. The bacteriums usually involved are Staphylococcus aureus and for contact lens wearers Pseudomonas aeruginosa.
- Fungal keratitis (cf. Fusarium, causing recent incidences of keratitis through the possible vector of Bausch & Lomb ReNu with MoistureLoc contact lens solution)
- Viral keratitis
- Herpes simplex keratitis. Viral infection of the cornea is often caused by the herpes simplex virus which frequently leaves what is called a 'dendritic ulcer'.
- Herpes zoster keratitis

## Other
- Exposure keratitis
- Photokeratitis - keratitis due to intense ultraviolet radiation exposure (e.g. snow blindness or welder's arc eye.)
- Ulcerative keratitis
- Contact lens acute red eye (CLARE) - a non-ulcerative sterile keratitis associated with colonization of Gram-negative bacteria on contact lenses
- Severe allergic response may lead to corneal inflammation and ulceration (i.e. vernal keratoconjunctivitis).
- Drug Induced -  Afatinib, Cyclopentolate, Diclofenac (ophthalmic), Doxorubicin Hydrochloride, Emedastine Difumarate, Moxifloxacin ophthalmic, Naphazoline , Nitisinone, Panitumumab, Pramipexole

# Causes

## Life Threatening Causes
Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated.
- Small pox

## Common Causes
- Adenovirus
- Contact lens
- Herpes simplex virus
- Injury

## Causes by Organ System

## Causes in Alphabetical Order
- Acanthamoeba
- Aciclovir
- Adenovirus
- Afatinib
- Amaurosis fugax
- Arc eye
- Aspergillus fumigatus
- Atopic dermatitis
- Bacillus cereus
- Balamuthia mandrillaris
- Behcet disease
- Betaxolol (ophthalmic)
- Bimatoprost
- Brimonidine (ophthalmic)
- Bromfenac
- Brucellosis
- Candida
- Canine herpesvirus
- Cogan syndrome
- Confocal laser scanning microscopy
- Congenital syphilis
- Conjunctivitis
- Connexin
- Contact lens
- Contact lens acute red eye
- Contaminated water
- Corneal dystrophy
- Corneal transplantation
- Corneal ulcer
- Corynebacterium diphtheriae
- Crab louse
- Cyclopentolate
- Dendritic ulcer
- Diclofenac (ophthalmic)
- Dorzolamide
- Doxorubicin hydrochloride
- Dry eyes
- Ectrodactyly-ectodermal dysplasia-cleft syndrome
- Ectropion
- Emedastine difumarate
- Enterobacteria
- Enterovirus
- Epidermolysis bullosa
- Epinastine
- Erythema elevatum diutinum
- Erythema multiforme
- Exophthalmos
- Facial nerve paralysis
- Facioscapulohumeral muscular dystrophy
- Feline viral rhinotracheitis
- Fungal keratitis
- Fusarium
- Graves' disease
- Graves ophthalmopathy
- Haemophilus influenzae
- Henoch-Schonlein purpura
- Herpes simplex keratitis
- Herpes simplex virus infection
- Herpes zoster
- Herpesviridae
- Herpetic keratitis
- Hydroxypropyl cellulose
- Ichthyosis
- Immune reconstitution inflammatory syndrome
- Incontinentia pigmenti
- Injury
- Jellyfish stings
- Keratitis-ichthyosis-deafness syndrome
- Keratoconjunctivitis
- Keratoconjunctivitis sicca
- KID syndrome
- Lagophthalmos
- LASIK
- Latanoprost
- Late congenital syphilitic oculopathy
- Lepromatous leprosy
- Listeria
- Lyme disease
- Mansonella ozzardi
- Measles
- Microsporidiosis
- Moraxella
- Moxifloxacin ophthalmic
- Mycobacterium
- Mycobacterium boenickei
- Mycobacterium brisbanense
- Mycobacterium houstonense
- Mycobacterium neworleansense
- Naegleria infection
- Naphazoline
- Natamycin
- Neisseria gonorrhea
- Nepafenac
- Nitisinone
- Nocardiosis
- Non-steroidal anti-inflammatory drug (topical)
- Ocular rosacea
- Oculotect
- Oculovestibuloauditory syndrome
- Olopatadine
- Onchocerciasis
- Orthokeratology
- Orthopoxvirus
- Panitumumab
- Pannus
- Parechovirus
- Phlyctenular keratoconjunctivitis
- Phosgene oxime
- Photokeratitis
- Phycomycosis
- Pityriasis rubra pilaris
- Plesiomonas shigelloides
- Pramipexole
- Pseudomonas aeruginosa
- Psittacosis
- Radial keratotomy
- Reactive arthritis
- Reiter's syndrome
- Relapsing polychondritis
- ReNu
- Rheumatoid arthritis
- Rheumatoid vasculitis
- Ribonucleotide reductase
- Scedosporium apiospermum
- Scleritis
- Scopolamine
- Serratia marcescens
- Shigella
- Sicca syndrome
- Sjogren's syndrome
- Smallpox
- Snow blindness
- Staphylococcus aureus
- Staphylococcus epidermidis
- Stevens-Johnson syndrome
- Streptococcus pneumoniae
- Superior limbic keratoconjunctivitis
- Syphilis
- Systemic lupus erythematosus
- Thygeson's superficial punctate keratopathy
- Topical anesthetic
- Toxic epidermal necrolysis
- Trachoma
- Travoprost
- Trifluridine
- Type II tyrosinemia
- Ultraviolet radiation
- Unoprostone
- Vaccinia
- Varicella-zoster virus
- Vasculitis
- Vernal keratoconjunctivitis
- Vidarabine
- Vitamin A deficiency
- Xeroderma pigmentosum

# Symptoms
The symptoms are often very similar to those of conjunctivitis, an inflammation of the conjunctiva, and photophobia. The eye turns very red and there may be sensitivity to light, and the eye may feel uncomfortable. In the later stages of more severe cases, there can be strong pain, loss of vision/blurriness, and pus may form.

# Diagnosis
Effective diagnosis is important in detecting this condition and subsequent treatment as keratitis is sometimes mistaken for an allergic conjunctivitis.

# Treatment
- Treatment depends on the cause of the keratitis.
- Microbial keratitis should be managed as bacterial keratitis until proven otherwise.
- Steroids are indicated in the management of keratitis to reduce inflammation that may damage the eye.

## Antimicrobial regimens

### Bacterial Keratitis
- 1. Causative pathogens
- Pseudomonas aeruginosa
- Staphylococcus epidermidis
- Staphylococcus aureus
- Streptococcus pneumoniae
- Serratia spp.
- Hemophilus spp.
- Moraxella spp.
- Neisseria gonorrhea
- Corynebacterium diphtheriae
- Listeria spp.
- Shigella spp.
- Nocardia spp.
- Mycobacterium spp.
- 2. Empiric antimicrobial therapy
- Preferred regimen (1): Ciprofloxacin 0.3% ophthalmic ointment q15min for 6 hours then q30min for the remainder of day 1 then q1h on day 2, then q4h on days 3-14
- Preferred regimen (2): Ofloxacin 0.3% ophthalmic ointment q2h for 2-3 weeks
- Preferred regimen (3): Levofloxacin 1.5% ophthalmic ointment q2h for 2-3 weeks
- Preferred regimen (4): Moxifloxacin 0.5% q1h on day 1 then q2h on day 2 then q4h on days 3-14
- Preferred regimen (5): Gatifloxacin 0.3% q1h on day 1 then q2h on day 2 then q4h on days 3-14
- Preferred regimen (6): Cefazolin 5% q30min to q1h on day 1 then q2h on day 2 then q4h on days 3-14  AND Tobramycin 5% ophthalmic ointment q1h on day 1 then q2h on day 2 then q4h on days 3-14 OR Gentamicin 1.5% ophthalmic ointment q30min to q1h on day 1 then q1h on day 2 then q4h on days 3-14)
- Alternative regimen (1), unresponsive keratitis: Vancomycin 5% q30 min on day 1 then q2h on day 2 then q4h on days 3-14 AND Amikacin 5% q1h on day 1 then q2h on day 2 then q4h on days 3-14
- Alternative regimen (2): Erythromycin 0.5% ophthalmic ointment qhs for 1 week AND (Amikacin 5% AND/OR Vancomycin 5% q30 min on day 1 then q2h on day 2 then q4h on days 3-14)
- Note (1) : Subconjunctival antibiotics may be helpful where there is imminent scleral spread or perforation or in cases where adherence to the treatment regimen is questionable.
- Note (2) : Systemic therapy is necessary for suspected gonococcal infection.
- 3. Pathogen-directed antimicrobial therapy
- 3.1 Non-streptococcal gram-positive bacteria
- Preferred regimen (1): Moxifloxacin 0.5% q1h on day 1 then q2h on day 2 then q4h on days 3-14
- Preferred regimen (2): Gatifloxacin 0.3% q1h on day 1 then q2h on day 2 then q4h on days 3-14
- Preferred regimen (3): Ciprofloxacin 0.3% ophthalmic ointment q15min for 6 hours then q30min for the remainder of day 1 then q1h on day 2, then q4h on days 3-14
- Preferred regimen (4): Ofloxacin 0.3% ophthalmic ointment q2h for 2-3 weeks
- Preferred regimen (5): Levofloxacin 1.5% ophthalmic ointment q2h for 2-3 weeks
- Preferred regimen (6): Cefazolin 5% q30min to q1h on day 1 then q1h on day 2 then q4h on days 3-14  AND Tobramycin 5% ophthalmic ointment q1h on day 1 then q2h on day 2 then q4h on days 3-14
- 3.2 Streptococcus pneumoniae
- Preferred regimen (1): Moxifloxacin 0.5% q1h on day 1 then q2h on day 2 then q4h on days 3-14
- Preferred regimen (2): Gatifloxacin 0.3% q1h on day 1 then q2h on day 2 then q4h on days 3-14
- Preferred regimen (3): Ciprofloxacin 0.3% ophthalmic ointment q15min for 6 hours then q30min for the remainder of day 1 then q1h on day 2, then q4h on days 3-14
- Preferred regimen (4): Ofloxacin 0.3% ophthalmic ointment q2h for 2-3 weeks
- Preferred regimen (5): Levofloxacin 1.5% ophthalmic ointment q2h for 2-3 weeks
- Preferred regimen (6): Cefazolin 5% q30min to q1h on day 1 then q1h on day 2 then q4h on days 3-14  AND Tobramycin 5% ophthalmic ointment q1h on day 1 then q2h on day 2 then q4h on days 3-14
- Alternative regimen (unresponsive keratitis): Vancomycin 5% q30 min on day 1 then q2h on day 2 then q4h on days 3-14 AND Amikacin 5% q1h on day 1 then q2h on day 2 then q4h on days 3-14
- 3.3 Nocardia spp.
- Preferred regimen (1): Vancomycin 5% q30 min on day 1 then q2h on day 2 then q4h on days 3-14 AND Amikacin 5% q1h on day 1 then q2h on day 2 then q4h on days 3-14
- Preferred regimen (2): Erythromycin 0.5% ophthalmic ointment qhs for 1 week AND (Amikacin 5% AND/OR Vancomycin 5% q30 min on day 1 then q2h on day 2 then q4h on days 3-14)
- 3.4 Gram-negative bacteria
- Preferred regimen (1): Moxifloxacin 0.5% q1h on day 1 then q2h on day 2 then q4h on days 3-14
- Preferred regimen (2): Gatifloxacin 0.3% q1h on day 1 then q2h on day 2 then q4h on days 3-14
- Preferred regimen (3): Ciprofloxacin 0.3% ophthalmic ointment q15min for 6 hours then q30min for the remainder of day 1 then q1h on day 2, then q4h on days 3-14
- Preferred regimen (4): Ofloxacin 0.3% ophthalmic ointment q2h for 2-3 weeks
- Preferred regimen (5): Levofloxacin 1.5% ophthalmic ointment q2h for 2-3 weeks
- Preferred regimen (6): Cefazolin 5% q30min to q1h on day 1 then q1h on day 2 then q4h on days 3-14  AND Tobramycin 5% ophthalmic ointment q1h on day 1 then q2h on day 2 then q4h on days 3-14
- 3.5 Anaerobes
- Preferred regimen (1): Ciprofloxacin 0.3% ophthalmic ointment q15min for 6 hours then q30min for the remainder of day 1 then q1h on day 2, then q4h on days 3-14
- Preferred regimen (2): Ofloxacin 0.3% ophthalmic ointment q2h for 2-3 weeks
- Preferred regimen (3): Levofloxacin 1.5% ophthalmic ointment q2h for 2-3 weeks

### Fungal (mycotic) Keratitis
- 1. Causative Pathogens.
- Candida spp.
- Fusarium spp.
- Aspergillus spp.
- Curvularia spp.
- 2. Empiric antimicrobial therapy
- Preferred regimen (1): Natamycin 5% ophthalmic suspension q30min to q1h for 2-3 weeks
- Preferred regimen (2): Fluconazole 1% ophthalmic suspension q1h for 2-3 weeks
- Preferred regimen (3): Natamycin 5% ophthalmic suspension q30min to q1h for 2-3 weeks AND Fluconazole 1% ophthalmic suspension q1h for 2-3 weeks
- Alternative regimen (1), unresponsive: Amphotericin B 0.15-0.25% prepared in distilled water q15min-q30min on day 1-2 then q1h to q2h for 2-3 weeks
- Alternative regimen (2), unresponsive: Natamycin 5% ophthalmic suspension q30min to q1h for 2-3 weeks AND Amphotericin B 0.15-0.25% prepared in distilled water q15min-q30min on day 1-2 then q1h to q2h for 2-3 weeks
- 3. Special considerations
- Immunocompromised status, spreading ulcer, impending perforation, true perforation
- Preferred regimen (1): Natamycin 5% ophthalmic suspension q30min to q1h for 2-3 weeks AND Fluconazole 1% ophthalmic suspension q1h for 2-3 weeks AND (Ketoconazole IV 200-400 mg q12h for 2-3 weeks OR Fluconazole IV 200 mg q12h for 2-3 weeks
- Preferred regimen (2): Natamycin 5% ophthalmic suspension q30min to q1h for 2-3 weeks AND Amphotericin B 0.15-0.25% prepared in distilled water q15min-q30min on day 1-2 then q1h to q2h for 2-3 weeks AND (Ketoconazole IV 200-400 mg q12h for 2-3 weeks OR Fluconazole IV 200 mg q12h for 2-3 weeks
- Note: Bacterial superinfection must be treated using Ciprofloxacin 0.3% ophthalmic ointment q15min for 6 hours then q30min for the remainder of day 1 then q1h on day 2, then q4h on days 3-14 OR (Cefazolin 5% q30min to q1h on day 1 then q1h on day 2 then q4h on days 3-14  AND Tobramycin 5% ophthalmic ointment q1h on day 1 then q2h on day 2 then q4h on days 3-14)

### Protozoal Keratitis
- 1. Causative pathogens
- Acanthamoeba spp.
- Microsporidia spp.
- 2. Empiric antimicrobial therapy
- Preferred regimen (1): Polyhexamethylene biguanide 0.02% ophthalmic ointment q1h for 1-2 weeks AND Chlorhexidine 0.02% ophthalmic ointment q1h for 1-2 weeks AND/OR (Propamidine 0.1% ophthalmic ointment q1h for 1-2 weeks OR Hexamidine 0.1% ophthalmic ointment q1h for 2 days then q1h for another 3 days)
- Preferred regimen (2): Propamidine 0.1% ophthalmic ointment q1h for 1-2 weeks AND Polyhexamethylene biguanide 0.02% ophthalmic ointment q1h for 1-2 weeks
- Preferred regimen (4): Propamidine ophthalmic ointment q1h for 1-2 weeks AND Chlorhexidine ophthalmic ointment q1h for 1-2 weeks
- Preferred regimen (4): Polyhexamethylene biguanide 0.02% ophthalmic ointment q1h for 1-2 weeks AND Hexamidine 0.1% ophthalmic ointment q1h for 2 days then q1h for another 3 days

### Viral Keratitis
- 1. Causative pathogens
- Herpes simplex virus (HSV)
- 2. Empiric antimicrobial therapy
- Preferred regimen (1): Acyclovir 3% ophthalmic ointment q5h for 2-3 weeks AND Homatropine 2% ophthalmic solution bid for 2-3 weeks
- Preferred regimen (2): Idoxuridine 0.1% ophthalmic solution q1h in daytime and 0.5% ophthalmic ointment qhs for 1 week then 0.1% ophthalmic solution q2h in daytime and 0.5% ophthalmic ointment qhs for 2-3 weeks AND Homatropine 2% ophthalmic solution bid for 2-3 weeks

### Contraindicated medications
Epithelial herpes simplex keratitis is considered an absolute contraindication to the use of the following medications:
- Fluorometholone
- Loteprednol
- Rimexolone
- Suprofen