Treatment of Keratitis (see references 2 & 3)



The Red Eye and Selected Ocular Emergencies

Thursday May 28, 2009

American College Health Association

2009 Annual Meeting

San Francisco, CA

Supplemental Handout

Frederick H. Bloom, O.D.

Director, Eye Care Services

University Health Services

University of Massachusetts

Amherst, MA 01003

413-577-5383

fbloom@uhs.umass.edu

Guidelines for Treatment of Conjunctivitis

Bacterial Conjunctivitis (other than chlamydial conjunctivitis)

- Prescribe a broad spectrum topical antibiotics

Tobrex drops– 1 drop 4 x day x 7 days or

Polytrim drops – 1 drop every 3 hrs up to maximum dose of 6 x day x 7 days

(approved for greater than 2 months of age)

Ilotycin ointment (Erythromycin ointment) – apply 4 x day x 7 days

(most patients do not like ointment as it blurs vision)

*Vigamox – 1 drop 3 x day x 7 days

*Zymar -1 drop every 2 hours (days 1 and 2) then 1 drop 4 x day (days 3 to 7)

* It is recommended to reserve 4th generation fluoroquinolones, Vigamox and Zymar, for keratitis, corneal ulcers, or contact lens wearers with suspicion of keratitis; approved for use in people greater than 1 year of age

Note: If you decide to prescribe a fluoroquinolone, it is recommended to prescribe a 4th generation fluoroquinolone rather than, the less expensive, 2nd or 3rd generation fluoroquinolones such as Ocuflox, Ciloxan, and Quixin, due to the 4th generation fluoroquinolones’ enhanced drug delivery capabilities, the improved activity against gram positive bacteria, and their lowered likelihood of causing resistance.

Chlamydial Conjunctivitis

Adult Inclusion Conjunctivitis

Laboratory testing – Aptima Genprobe Assay (proprietary test of Genprobe – uses TMA - transport mediated amplification – DNA probe looking for RNA target (very specific)

Systemic antibiotics: Azithromycin 1G x 1 day single dose by mouth, Doxycycline 100mg orally 2 x day x 14 days or Erythromycin 500 mg orally 4 x day x 14 days to patient and sexual partners

Topical medication (erythromycin ophthalmic ointment) 4 x per day x 3 weeks

* Tetracyclines are contraindicated in children under 8 years, pregnant women, and nursing mothers

Warm compresses

Viral Conjunctivitis

- Educate the patient in appropriate infection control and hygiene to prevent the spread of the infection to others

- Apply appropriate infection control procedures in your office to prevent spread of the infection to you, your staff and your other patients

- Warm or cold compress, artificial tears, decongestant/antihistamine (Naphcon A)

- Adjunct po medications

Allergic Conjunctivitis

• Avoidance

• Cold compress

• OTC artificial tear lubricants (Eye wash or Theratears or Genteal or Systane eye drops)

1 drop 4 x day

• OTC Vasoconstrictors (e.g. visine or murine)

• Topical antihistamines?, otc: Zaditor or Alaway (ketotifen fumarate)

• Vasoconstrictor/Antihistamines (Naphcon A) 1 drop 4 x per day

• Oral antihistamines – beware of ocular dryness side effect

• Topical Mast cell stabilizers/Antihistamines: Patanol (Olopatadine 0.1%) 1 drop 2 x day at intervals of 6 to 8 hrs and Pataday (Olopatadine 0.2%) 1 drop 1 x per day each eye *

• Non-steroidal anti-inflammatory agents (Ibuprofen or topical Acular LS 0.4%. However, topical Acular LS (1 drop 4 x per day) is generally not comfortable for patients with allergic conjunctivitis and I generally do not prescribe Acular for allergic conjunctivitis

• Steroids – refer

• In very mild cases of allergic conjunctivitis, when it seems appropriate for the patient to wear contact lenses for short periods, it is recommended that patients wait 10 to 15 minutes after instilling Patanol/Pataday, Naphcon A, or other eye drops before inserting their contact lenses

Recommendations for Culturing and Lab Testing for Most Conjunctivitis

• Routine bacterial culturing of conjunctivitis is not recommended. However, it is recommended in cases of conjunctivitis not responding to standard treatment after 2-3 weeks, recurrent conjunctivitis, or severe purulent conjunctivitis

• Chlamydial assaying (Aptima/Genprobe - transport mediated amplification (proprietary test of genprobe) uses a DNA probe looking for RNA target, very specific, for Chlamydia Trachomatis and Neisseria Gonorrhoeae) is also recommended in cases of chronic follicular conjunctivitis i.e. lasting longer than 2-3 weeks in individuals who are sexually active

Conjunctivitis Pearls

• A red eye with pain, tearing, and/or decreased vision is usually not conjunctivitis

• Chronic follicular conjunctivitis, greater than 2 weeks, especially in sexually active

individuals, rule out chlamydial conjunctivitis, check sexual partners – genital

symptoms, asymptomatic at least 50% of time

• Preauricular adenopathy is usually viral although can be present in acute hordeolum

• Systemic medications: e.g. Ask if patient is taking Accutane – rule out dry eye, conjunctivitis,

night vision problems

• Medicamentosa – e.g. Aminoglycocides (Tobrex, Gentamicin, Neomycin) toxic to cornea

• Remember hygiene for patient and you; advise patients to wash hands if they touch their eyes,

use a separate towel or pillow at home, don’t wear or share make-up, and don’t go swimming

Classical Presentation of the Differential Diagnosis of the Red Eye

| | CONJUNCTIVITIS |IRITIS |ACUTE GLAUCOMA |KERATITIS* |EPISCLERITIS |

| | | | | |SCLERITIS |

| |Viral |Bacterial |Allergic | | | | |

|INCIDENCE |Extremely Common |Common |Uncommon |Extremely common |Uncommon |

|DISCHARGE |Serous |Mucopurulent |Whitish, stringy, ropy mucus |Watery |Watery |Watery |Usually none |

|DISCOMFT OR PAIN |Grittiness |Grittiness |Itching |Pain, Photophobia |Severe pain, |Moderate pain, photophobia|Varies |

| | | | | |photophobia, | | |

| | | | | |vomiting | | |

|COMMENTS |- Follicles often present |Most common causes: |- Papillae often present | |

| |- Often has tender preauricular|Staphylococcus aureus |- May have chemosis (swelling of | |

| |adenopathy |Streptococcus pneumoniae |conjunctiva) | |

| |- May have URI |Haemophilus species |R/O allergy to medication | |

| | | |R/O chemical injury (usually | |

| | | |obvious by Hx) | |

|VISION |Not blurred |Usually slightly blurred |Markedly blurred |May be blurred |Usually not affected|

| | | | | |initially |

|INJECTION |Conjunctival or Diffuse |Ciliary |Diffuse |Ciliary |Segmental or diffuse|

|CORNEA |Clear, if pure conjunctivitis |Keratitic, precipitates |Steamy, corneal |Not clear, possible |Usually clear |

| | | |edema |infiltrates or staining |initially |

|PUPIL SIZE |Normal |Usually small (miotic) |Mid-dilated |Normal |Normal |

| | |Can have traumatic | | | |

| | |mydriasis (dilated) | | | |

|PUPILLARY LIGHT |Normal |Poor |Fixed, no response |Normal |Normal |

|RESPONSE | | | | | |

|INTEROCULAR PRESSURE|Normal |Normal to low |Elevated |Normal |Normal |

| |(Don’t do on infected eye) | | | | |

|ANTERIOR CHAMBER |Normal |Cells and flares |Shallow |Normal |Clear |

• Always compare 2 eyes

* For the purpose of this chart, keratitis refers to any inflammation or infection of the cornea: corneal abrasions, corneal inflammations, corneal ulcers that could be bacterial, viral including herpes simplex with the classic epithelial dendritic staining, herpes zoster, fungal, or parasitic such as acanthemoeba, or even sterile inflammations

Note: There may be reduced corneal sensitivity with herpes simplex keratitis and with herpes zoster if the tip of the nose is involved usually there is a higher risk of ocular involvement due to the distribution of the nasociliary branch of the ophthalmic division of the trigeminal, fifth cranial nerve

Treatment of Keratitis (see references 2 & 3)

- In general, refer to eye doctor after initial treatment

Bacterial Keratitis *

- “Small Infiltrates (2mm and/or more central corneal ulcers should be referred for culturing and more aggressive medical treatment

* The most common causes of bacterial keratitis are staphylococcus, streptococcus, pseudomonas, and moraxella species

Viral Keratitis

- “HSV Epithelial Keratitis: Refer to eye doctor. Topical antiviral (trifluridine [Viroptic] (the treatment recommended for viroptic is 9 times/day but many doctors start at 5 times/day because it has been shown to be equally effective and less toxic in most cases) 9 times/day or vidarabine monohydrate [Vira-A] 5 times/day for 10-14 days; consider oral antiviral agent (acyclovir 400mg po tid for 10-21 days, then prophylaxis with 400mg bid for up to 1 year [or longer after penetrating keratoplasty]), ? debride dendrite.”

- “HZV: Refer to eye doctor. Systemic antiviral agent (acyclovir 800 mg po 5 times a day for 7-10 days, or famciclovir 500 mg po or valacyclovir 1 g po tid for 7 days), topical steroids (prednisolone acetate 1% qid to q4h, then taper slowly over months), cycloplegic agent (scopolamine 0.25% bid to qid); add topical antibiotic ointment (erythromycin or bacitracin tid) if conjuctival or coneal involvement. Consider tricyclic antidepressants, Neurontin, pain medications, capsaicin cream, or Lidoderm patches for postherpetic neuralgia.”

- May require treatment of increased inter ocular pressure

Sterile Keratitis

- Symptoms usually less severe, infiltrate often more peripheral cornea

- Treatment similar to bacterial keratitis

Fungal Keratitis*

- Satellite lesions surrounded by primary lesion, associated with vegetative corneal abrasion, especially in corneal abrasion and some contact lens solution

- Treatment – Natomycin 5% or Amphotericn B (additional treatment beyond the scope of this talk)

Acanthomoeba Keratitis* (parasite)

- Associated with contact lens wear; hot tub use?, swimming in fresh water?

- At 3 to 8 weeks corneal stromal ring infiltrates (treatment beyond scope of this talk)

* more rare

Clinical Pearls

With a corneal ulcer there is often a presence of an infiltrate – loss of clarity of cornea- white patch representing cellular inflammation

- Discontinue contact lens wear

- Never patch a corneal ulcer

- There is a greater risk of gram negative infection with contact lens wear, and with keratitis compared with conjunctivitis, therefore cover with anti-pseudomal eye medication e.g. Vigamox or Zymar

- Cycloplegics may be needed (usually used sparingly as they may have a big impact on patient functions)

- P.O pain medication may be needed

- Immunosuppressant patients are at greater risk of infection

- Smokers and contact lens wearers are at a greater risk of keratitis

- Contact lens wearers who sleep in contact lenses have a 10x greater risk of infection

- Ulcers require daily follow-up initially, and severe ones require hospital admission. Most keratitis at UHS is relatively mild and can be treated with 4th generation fluoroquinolones e.g. Vigamox or Zymar, usually hourly initially

- If organism is in doubt, treat as a bacterial ulcer until culture results return

|Table 1: Antivirals |

|Mechanism of Action (MOA): Inhibit DNA replication |

|Generic |Trade |Formulations |Condition |Dosage |

|acyclovir |Zovirax |200mg capsule; 400mg and |VZV |800mg 5x/d for 7 to 10 |

| |(GlaxoSmithKline) |800mg tablets; 200mg/5ml | |days |

| | |suspension | | |

| | | |HSV |400mg 5x/d for 7 |

| | | | |days |

| | | |HSV (pediatric) |20mg/kg/d divided q.i.d. |

| | | | |for 7 days |

| | | |HSV prophylaxis |400mg b.i.d. |

|valacyclovir |Valtrex |500mg |VZV |1g t.i.d. for 7 to 10 |

| |(GlaxoSmithKline) |1000mg | |days |

| | |(1g) caplets | | |

| | | |HSV |500mg t.i.d. for 7 days |

| | | |HSV prophylaxis |500mg *once per day |

| | | | | |

|famciclovir |Famvir |125mg |VZV |500mg t.i.d. for 7 to 10 |

| |(Novartis) |250mg | |day |

| | |500mg tablets | | |

| | | |HSV |250mg t.i.d. for 7 days |

| | | |HSV prophylaxis |250mg b.i.d. |

The information in the tables is meant as a guide and is intended for healthy adults who have no contraindications to the medication.

Review of Optometry MAY 15, 2005 and *amended after discussion with Jimmy D. Bartlett, OD April 26, 2009

Anterior Uveitis (Iritis, Iridocyclitits) (see references 2 & 3)

Possible Symptoms – red eye, pain, photophobia, decreased vision

Possible Signs – cells and floaters in anterior chamber, ciliary flush, and keratic precipitates, or high intra ocular pressure, and usually miosis, unless traumatic mydriasis, eye pain if shine a light in the non involved eye usually from ciliary spasm

“Classifications – acute, chronic, recurrent

granulomatous vs. non granulomatous

traumatic vs. non traumatic

location in uveal tract

Etiology – Most commonly idiopathic or autoimmune, but it is critical to rule out causes such

As infection, malignancy, medication, and trauma

- Idiopathic

- Traumatic

- Herpes simplex and Herpes Zoxter Ophthalmicus

- Lyme Disease

- Syphilis

- Tuberculosis

- HLA- B27 associated anterior uveitis

o Ankylosing Spondylitis

o Reiter’s Syndrome

o Psoriatic Arthritis

o Inflammatory Bowel Disease

- Whipple’s Disease

- Behcet’s disease (acute)

- Glaucomatocyclitic crisis (Posner-Schlossman syndrome, acute)

- Kawasaki’s disease (acute)

- Drug use (acute)

- Interstitial nephritis

- Other autoimmune disease (acute and chronic)

- Juvenile rheumatoid arthritis (chronic)

- Fuchs’ heterochromic iridocyclitis (chronic)

- Postoperative or trauma (chronic)

- HLA associations (located on chromosome 6)

- Sarcoid”

Treatment - Refer to the eye doctor for consideration of the following:

- Topical steroids

- Cyclopegics

- Treat elevated intra ocular pressure

- PO NSAI

- PO steroids and/or subtenon steroid injection

- Treat underlying systemic disease

- Immunosuppression chemotherapy and other treatment

Prognosis

Depends on etiology. Most have good visual prognosis. Traumatic iritis is generally easier to treat unless there is concomitant ocular injury to other structures

Papilledema (may be life threatening) (see references 2,3 & 4)

Definition

Optic nerve swelling caused by increased intracranial pressure

Symptoms

Asymptomatic; may have headache, nausea, emesis, transient visual obscurations (lasting seconds), diplopia, altered mental status, or other neurologic deficits

Signs

Critical. Bilaterally swollen, hyperemic discs, blurred disc margins and elevated discs,

And the absence of optic cup.

Other. Papillary or peripapillary retinal hemorrhages (often flame shaped); loss of venous

Pulsations (20% of the normal population do not have venous pulsations); dilated,

Tortuous retinal veins; loss of physiological cup, concentric folds or lines

Management:

Refer and/or work up stat as an emergency and then treat underlying cause

Etiology of Papilledema – optic nerve swelling due to increased intracranial pressure

- Primary and metastatic intracranial mass

- Pseudotumor cerebri (often occurs in young, overweight females) (idiopathic intraocular hypertension)

- Aqueductal stenosis producing hydrocephalus

- Subdural and epidural hematomas (From trauma)

- Subarachnoid hemorrhage

- Arteriovenous malformation

- Brain abscess

- Meningitis

- Encephalitis

- Intracranial venous sinus thrombosis

Differential Diagnosis of other causes of disc swelling without increased intracranial pressure

- Pseudopapilledema

- Papillitis

- Hypertensive optic neuropathy

- Central retinal vein occlusion

- Ischemic optic neuropathy

- Optic disc vasculitis

- Infiltration of the optic disc

- Leber optic neuropathy

- Orbital optic nerve tumors

- Diabetic papillitis

- Graves ophthalmopathy

- Uveitis

Optic disc swelling in a patient with a history of leukemia is often a visually threatening sign of leukemic infiltration of the optic nerve. Immediate radiation therapy is usually required to preserve vision”

Clinical Pearls:

- papilledema is a medical emergency

- work up stat

- approximately 80% of the normal population has spontaneous venous pulsations (SVP)

- SVP usually disappears at approximately 225mm water cerebral spinal fluid pressure. The opening pressure reading as measured by lumbar puncture (always preceded by a head scan to rule out a true mass) in patients with benign intracranial hypertension (a.k.a pseudo tumor cerebri) is usually between 250 and 600 mm H20

- loss of previously seen SVP is the earliest ophthalmoscopic sign of papilledema

- papilledema may develop over 8 to 24 hours and the optic nerve swelling usually slowly decongests over a number of weeks or months”

- Not all cases of pseudo tumor cerebri are in overweight women, in fact, most of the cases I have seen at the UHS were not in overweight women. Rule out that pseudo tumor cerebri is not caused by some systemic medication e.g. tetracycline

References

1. Duane’s Clinical Ophthalmology. New York: Lippincott Williams, & Wilkins.

2. Kaiser MD, Peter, Neil Friedman, MD, & Roberto Pineda II, MD. The Massachusetts Eye and

Ear Infirmary Illustrated Manual of Ophthalmology. Philadelphia: Saunders, 2004.

3. Kunimoto, MD, Derek, Kunal Kanitkar, MD, & Mary Makar, MD. The Willis Eye Manual. Philadelphia: Lippincott Williams & Wilkins, 2004.

4. Smith, MD, J. Lawton. The Optic Nerve. Miami: Neuro-Ophthalmology Tapes, 1995.

5. My own clinical experience of seeing over 100,000 patients over 30 years and consulting with over 35 ophthalmologists (for patients I referred). Many of those 35 ophthalmologists have sub specialties in cornea, pediatric ophthalmology, strabismus, uveitis, cataract surgery, retina, oculo plastics and orbits, laser refractive surgery, and neuro ophthalmology

6. American Academy of Ophthalmology Cornea/External Disease Panel. (2003) “Preferred Practice Pattern: Conjunctivitis.” American Academy of Ophthalmolgy

7. American Optometric Association Consensus Panel on Care of the Patient with Conjunctivitis. (2002) “Care of the Patient with Conjunctivitis” American Optometric Association

8. The Willis Eye Manual, Office and Emergency Room Diagnosis and Treatment of Eye Disease. Kunimoto et al. Lippincott Williams & Wilkins, 2004.

9. The Massachusetts Department of Public Health – Division of STD Prevention – 2006 Sexually Transmitted Diseases Treatment Guidelines

10. Huang, David G. (2004). “Fluoroquinolone Resistance in Ophthalmology and the Potential Role for Newer Ophthalmic Fluoroquinolones.” Survey of Ophthalmology, 49, Supplement 2, S79.

11. Parmar, Pragya, Amjad Salman, Catti Munusamy Kalavathy, Jayaraman Kaliamurthy, Duraisamy Arvind Prasanth, Philip Aloysius Thomas, and Christdas Arul Nelson Jesudasan. (2006). “Comparison of Topical Gatifloxacin 0.3% and Ciprofloxacin 0.3% for the Treatment of Bacterial Keratitis.” Am J Ophthalmology, 141, 282-286.

Disclosure and acknowledgement of source of colored eye slides:

Most of the slides I took myself and were of patients I personally examined. A small number of slides were either lent to me by my colleagues or obtained from MedCom, a professional slide service. Additionally, a few slides were also taken from the World Wide Web to enhance learning. If you have any questions about the sources of the slides, please contact me. Thank you.

A special acknowledgement and heartfelt thank you to Emily Wegner, Karen Dunbar-Scully, and Pierre Rouzier M.D. for their excellent and superb assistance with the typing, editing, technical, and clinical aspects of preparing this PowerPoint presentation.

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