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A case of Herpetiform Keratitis- Clinical evaluation and important considerations.

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A case of Herpetiform Keratitis- Clinical evaluation and important considerations: A Resident Clinical Pearl

Bonnie He, PGY1

Ophthalmology, Dalhousie University

Reviewed by: Dr. Cherie Adams

Copyedited by: Dr. Mandy Peach

Case

A 68-year-old female presented to SJRH Emergency Department with a three-day history of atraumatic worsening of right eye pain, photophobia, and decreased vision. She denied any experience of flashing lights or “curtain falling”. She reported a long-standing history of glaucoma for which she was previously prescribed brimonidine (alpha-agonist) ophthalmic drops and was prescribed travoprost (prostaglandin) ophthalmic drops approximately one week prior to presentation. Additional ophthalmologic history revealed used of glasses, but not contact lenses, and bilateral cataract surgery two years previously. Of particular note, she recounted an episode of “sores from her upper lip along the side of her nose to right lower eyelid” in the past for which she was treated with oral valacyclovir. Further history positive for hypertension, for which she is prescribed ramipril, and type 2 diabetes mellitus, for which is is prescribed metformin. She is a retired schoolteacher, non-smoker, social drinker and denies any recreational drug use.
Visual acuity from 20 feet with spectacle correction revealed was 20/100 on the right (OD) and 20/30+1 on the left (OS). Her intraocular pressures were OD 17 and OS 19. Examination revealed mild upper and lower eyelid edema and moderate conjunctival injection. Fluorescein staining of the right cornea revealed four small dendritic epithelial defects (Figure 1) at about the 6 o’clock position. External and slit lamp examination of the left eye was normal. Fundoscopic examination to check the optic disc, macula, retinal vessels, and periphery were deferred.

Figure 1A: 4 small dendritic epithelial lesions can be seen at the 6’oclock position.

 

Figure 1B: Classic dendritic corneal epithelial lesions 17.

OPHTHALMOLGIC ASSSESSMENT:

Ocular complaints are common in emergency care settings. Yet, the quantity and quality of ophthalmology education varies significantly across Canada, with both medical students and residents report receiving insufficient ophthalmic medical education from medical education curricula.1-3
Proper history and physical examination taking skills are crucial to the appropriate management of patients with a red eye. The American Academy of Ophthalmology recommends the 8-point physical exam as a systematic approach to any eye problems:

  1. Visual acuity
    • Position the patient 20ft or 6m away from the Snellen chart to test for distance vision
    • Document whether it is their best corrected visual acuity, (ie. did they have their glasses or contact lens on at the time of the exam)
  2. Pupils
    • In dim room light, check for:
      1. Direct response by looking for pupil constriction in the eye being shined
      2. Consensual response by looking for pupil constriction in the other eye (eye that is not being shined)
  • Rapid Afferent Pupillary Defect (RAPD) with the swinging light test by shining light back and front between eyes
  1. Extraocular motility and alignment
    • Conduct a “H test” to test for the 9 cardinal positions of gaze by tracing out the letter “H” in the air while monitor their eyes for 3 S’s: speed, smoothness, and symmetry
    • Ask patient to follow your finger with their eyes while keeping their head still in the center and note for any double vision at certain gazes
  2. Intraocular pressure
    • The Icare tonometer requires no local anesthetic
    • Insert probe into tonometer and anchor the tonometer to the seated patient’s eyebrow.
    • Slowly bring tonometer probe towards patient light until the light turns green – now you’re ready to press the button that will automatically measure the patient’s intraocular pressure
  3. Confrontation visual fields
    • At about 1 arm’s-length away, test each eye individually by holding up 1 or 2 fingers and ask patient how many fingers they see
    • Ask patient to close their OS and fixate on your nose. Close your OS to assess with your open OD.
    • To check OS, ask the patient to close their OD and fixate on your nose. Close your OD to assess with your open OS.
  4. External examination
    • Assess for any obvious globe rupture, ecchymoses, deformities or lesions around the eye
    • Check to see if there’s any ptosis (lid drooping)
  5. Slit lamp examination (watch this video to learn how to perform a slit lamp exam: https://www.youtube.com/watch?v=gHW5OYj1Gf8
    • Assess for the following structures
    • Lids/lashes/lacrimal system: edema, erythema, lesions
    • Conjunctiva/sclera: injection, subconjunctival hemorrhage
    • Cornea: foreign body, fluorescein stain + cobalt blue light to assess corneal integrity (ie. corneal abrasions, herpetic dendrites), Seidel test (leakage of aqueous humour)
    • Iris: round (normal) vs. peaked (abnormal)
    • Anterior chamber: any hyphema, hypopyon, cells, flare
    • Lens: opacity
  6. Fundoscopic examination
    • In the emergency department, fundoscopy is typically undertaken in the undilated eye.
    • May consider dilating the eye with tropicamide (dilating drop) to visualize the back of the eye with the slit lamp or direct ophthalmoscope
    • Assess for the following structures:
      1. Optic nerve: cup-to-disc ratio, pallor, symmetry between eyes
      2. Macula: foveal light reflex
  • Vessels: Arteriovenous (AV) nicking, silver or copper wiring,
  1. Periphery: bleeding

DISCUSSION:

Given the patient’s endorsed history suggestive of ipsilateral V2 herpes zoster and classic dendritic corneal lesions, the leading differential diagnosis for her acute on chronic ocular pain in this case would be zoster keratitis, though herpes keratitis should also be considered, particularly in patients with identified history and recent episode of orolabial cutaneous HSV. Interestingly, she was started on travoprost for her glaucoma a week prior to her presentation. Topical ocular hypotensive agents, including travoprost, are known to have a myriad local and systemic side effects including: superficial punctate keratitis, corneal erosion, bradycardia, hypotension, and bronchoconstriction, are common.4,5 However, of particular interest in this case,  multiple clinical and animal studies have reported that topical prostaglandins for ocular hypertension are culprits  associated with herpes simplex virus (HSV) keratitis or varicella-zoster virus (VZV) keratitis.6-13 It is thought that prostaglandin analogues such as travaprost may induce the reactivation of HSV keratitis by releasing endogenous prostaglandins in the iris and ciliary muscles.9,14-16 Therefore it could also be very well possible that she may have developed HSV keratitis.

 

Irrespective of which differential was truly causing this patient’s symptoms the antiviral treatment for zoster ophthalmicus and HSV keratitis are the same: valocylcovir 1g TID PO x 7 days (or acyclovir 800mg po five times daily if cost of valcyclovir is prohibitive) and arrangements were made for next-day ophthalmologist consultation.

 

BOTTOM LINE:

Always take a thorough ophthalmologic history for patients with ocular complaints, including complete medication history.

Always ask about contact lens use in a history in any patient with a painful red eye.

Always conduct a complete physical exam for patients with ophthalmologic complaints using the AAO 8-point framework described above.


REFERENCES

  1. Sim D, Hussain A, Tebbal A, Daly S, Pringle E, Ionides A. National survey of the management of eye emergencies in the accident and emergency departments by senior house officers: 10 years on—has anything changed? Emerg Med J. 2008;25(2):76-77. http://emj.bmj.com/content/25/2/76.abstract. doi:10.1136/emj.2007.049999.
  2. Noble J, Somal K, Gill HS, Lam W. An analysis of undergraduate ophthalmology training in Canada. Canadian Journal of Ophthalmology. 2009;44(5):513-518. http://www.sciencedirect.com/science/article/pii/S0008418209801130. doi:https://doi.org/10.3129/i09-127.
  3. Gostimir M, Sharma RA, Bhatti A. Status of Canadian undergraduate medical education in ophthalmology. Canadian Journal of Ophthalmology. 2018;53(5):474-479. http://www.sciencedirect.com.ezproxy.library.ubc.ca/science/article/pii/S0008418216309553. doi:https://doi-org.ezproxy.library.ubc.ca/10.1016/j.jcjo.2017.11.015.
  4. Inoue K. Managing adverse effects of glaucoma medications. Clinical ophthalmology (Auckland, N.Z.). 2014;8:903-913. https://pubmed.ncbi.nlm.nih.gov/24872675 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4025938/. doi:10.2147/OPTH.S44708.
  5. Anwar Z, Wellik SR, Galor A. Glaucoma therapy and ocular surface disease: current literature and recommendations. Curr Opin Ophthalmol. 2013;24(2):136-143. doi:10.1097/ICU.0b013e32835c8aba [doi].
  6. Kroll DM, Schuman JS. Reactivation of herpes simplex virus keratitis after initiating bimatoprost treatment for glaucoma. Am J Ophthalmol. 2002;133(3):401-403. doi:S0002939401013605 [pii].
  7. Wand M, Gilbert CM, Liesegang TJ. Latanoprost and herpes simplex keratitis. Am J Ophthalmol. 1999;127(5):602-604. doi:S0002939499000501 [pii].
  8. Alm A, Grierson I, Shields MB. Side effects associated with prostaglandin analog therapy. Surv Ophthalmol. 2008;53 Suppl1:93. doi:10.1016/j.survophthal.2008.08.004 [doi].
  9. Soomro MZ, Moin M, Attaulla I. Latanoprost and Herpetic Keratitis. Pakistan Journal of Ophthalmology. 2011;27(4).
  10. Kothari MT, Mehta BK, Asher NS, Kothari KJ. Recurrence of bilateral herpes simplex virus keratitis following bimatoprost use. Indian J Ophthalmol. 2006;54(1):47-48. doi:10.4103/0301-4738.21617 [doi].
  11. Ekatomatis P. Herpes simplex dendritic keratitis after treatment with latanoprost for primary open angle glaucoma. Br J Ophthalmol. 2001;85(8):1008-1009. doi:10.1136/bjo.85.8.1007a [doi].
  12. Morales J, Shihab ZM, Brown SM, Hodges MR. Herpes simplex virus dermatitis in patients using latanoprost. Am J Ophthalmol. 2001;132(1):114-116. doi:S0002939401010121 [pii].
  13. Villegas VM, Diaz L, Izquierdo NJ. Herpetic keratitis in a patient who used two different prostaglandin analogue ophthalmic solutions: a case report. P R Health Sci J. 2008;27:348+. https://link.gale.com/apps/doc/A189052227/HRCA?u=anon~6a050068&sid=googleScholar&xid=2c140d29.
  14. Dios Castro E, Maquet Dusart JA. Latanoprost-associated recurrent herpes simplex keratitis. Arch Soc Esp Oftalmol. 2000;75(11):775-778.
  15. Gordon YJ, Yates KA, Mah FS, Romanowski EG. The effects of Xalatan on the recovery of ocular herpes simplex virus type 1 (HSV-1) in the induced reactivation and spontaneous shedding rabbit models. J Ocul Pharmacol Ther. 2003;19(3):233-245. doi:10.1089/108076803321908356 [doi].
  16. Kaufman HE, Varnell ED, Toshida H, Kanai A, Thompson HW, Bazan NG. Effects of topical unoprostone and latanoprost on acute and recurrent herpetic keratitis in the rabbit. Am J Ophthalmol. 2001;131(5):643-646. doi:S0002939400009107 [pii].
  17. Yu, Hubert (2019) Canadiem Medical Concepts: Approach to Corneal Disorders in the ED

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A Case of Herpes Simplex Virus Keratitis in The Emergency Department

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A Case of Herpes Simplex Virus Keratitis in The Emergency Department – A Medical Student Clinical Pearl

Patrick Gallagher, MED III

MUN Class of 2022

Reviewed by Dr. Robin Clouston

Copyedited by Dr. Mandy Peach

Case

A 53-year-old female presents to the emergency department with a two-day history of left-eye pain, which she describes as “something being stuck in her eye.” The patient endorses left eye tearing, pruritis, and photophobia. She notes that her eye has been “blurry” since she awoke this morning. The patient denies any infectious symptoms at present but states that a cold sore erupted on her upper lip seven days ago. She does not use contact lenses.

Past medical history: T2DM and hypothyroidism.

Past surgical history: None.

Medications: Metformin 500 mg OD and Synthroid 125 mcg OD.

Physical exam:

Upon inspection, the patient has conjunctival injection and tearing in the left eye. Mild periorbital edema and erythema is noted. The patient’s pupils are equal and reactive to light, and visual acuity is 20/20 in the left eye and 20/40 on the left eye. Extraocular eye movements and visual fields are normal. The patient has decreased corneal sensation.

On slit lamp examination using fluorescein-based dye, a small branching dendritic ulcer was seen (Figure 1).

Figure 1: Dendritic ulcer noted on slit-lamp exam with fluorescein-based dye.

 

What is the differential diagnosis of dendrites?

• Herpes simplex keratitis
• Acanthamoeba keratitis
• Other keratitis caused by Varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein–Barr virus (EBV), or adenovirus.
• Dendritiform keratopathy
• Ramous epithelial changes
• Limbal stem cell deficiency
• Drug induced corneal changes (epinephrine, antivirals, beta-blockers) 1,2

Herpes simplex virus keratitis :

Herpes simplex is a DNA virus that can cause a wide variety of infections, most commonly involving the mouth, genitalia, and eyes3. While HSV-1 and HSV-2 can involve the eye, HSV-1 is the most common cause of keratitis1. Herpes simplex keratitis (HSK) is characterized by recurrent infections of the corneal epithelium and stroma2. HSK can be classified as primary or recurrent and further divided into three subtypes: epithelial, stromal, and endothelial3. Epithelial keratitis is the most commons subtype of ocular herpes (50% to 80%)2.

Herpes simplex virus (HSV) infections are the leading cause of infectious corneal blindness in developed countries3. It is estimated that 1.5 million people worldwide experience HSV keratitis every year2.

Pathophysiology:

Primary HSV eye infections occur when the virus enters mucous membranes by direct contact. This initial infection is usually subclinical, but it can cause unilateral blepharitis, follicular conjunctivitis, and occasional epithelial keratitis (Figure 2)4. The initial infection is typically asymptomatic, and it occurs in children less than five years old5.

Figure 2: Pictorial representation of blepharitis (inflammation of the eyelid), keratitis (inflammation of cornea), conjunctivitis (inflammation of conjunctiva), and ocular anatomy. Diagram retrieved from 7

After the initial infection, the virus can remain latent in the ophthalmic division of the trigeminal ganglion for the lifetime of the host. HSV reactivation in the latently infected ganglia can lead to corneal scarring, thinning, stromal opacity, and neovascularization5. The cumulative effect of numerous infections results in vision loss and eventually blindness if left untreated.

History and physical:

Diagnosis of HSK is primarily diagnosed by clinical presentation on slit lamp exam using fluorescein and either rose bengal or lissamine green3. However, it is crucial to complete a thorough history and physical exam to narrow the differential diagnosis (Table 1).

Table 1: Key points on history and physical

Figure 3: Slit-lamp corneal findings for patient’s diagnosed with HSV epithelial keratitis. A: Classic dendritic lesion with terminal bulbs. B: More advanced dendritic lesion presenting as geographic ulcer. Figure modified from 6.

Investigations:

The diagnosis of HSVK is based off of clinical findings and does not require additional investigations; however, for atypical lesions, polymerase chain reaction has been used to confirm HSVK. Enzyme-linked immunosorbent assay and viral cultures are also effective in the diagnosis of the HSVK subgroups3.

Treatment/management of HSVK in the emergency department:

In the emergency department, typical findings on the slit lamp exam is diagnostic for epithelial HSVK.

Care providers should initiate treatment immediately to reduce the risk of complications; however, the patient must be referred to ophthalmology within the next few days for follow-up.

Topical and oral antiviral treatments effectively treat epithelial HSVK, although no topical ophthalmic antivirals are currently available in Canada7. It is crucial to adjust the dose of oral antivirals according to the patient’s renal function. See Table 2 for available oral antiviral treatments. For symptomatic management, artificial tears or eye lubricants can ease eye discomfort and over-the-counter analgesics can help relieve pain7.

Table 2: Oral antiviral treatment for epithelial HSVK in adults. Modified from 7

Back to the case:

Given our patient’s classic symptoms of epithelial HSVK (conjunctival injection, tearing, vision changes, foreign body sensation, photophobia, hx of HSV infection) and finding of dendritic ulcers on slit lamp examination, we treated this case as epithelial HSVK until proven otherwise. Therefore, we prescribed the patient valacyclovir 1000mg PO TID and arranged an urgent ophthalmology consult for the following day.

References:

  1. Roozbahani, M., & Hammersmith, K. M. (2018). Management of herpes simplex virus epithelial keratitis. Current opinion in ophthalmology, 29(4): 360-364.

  2. Wilhelmus, K. R. (2015). Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis. Cochrane Database of Systematic Reviews, 1.

  3. Azher, T. N., Yin, X. T., Tajfirouz, D., Huang, A. J., & Stuart, P. M. (2017). Herpes simplex keratitis: challenges in diagnosis and clinical management. Clinical Ophthalmology, 11:185–191.

  4. Sibley, D., & Larkin, D. F. (2020). Update on Herpes simplex keratitis management. Eye, 34: 2219–2226.

  5. Toma, H. S., Murina, A.T., Areaux, R.G., Neumann, D.M., & Bhattacharjee, P.S. (2008). Ocular HSV-1 Latency, Reactivation and Recurrent Disease. Seminars in Ophthalmology, 23(4), 249–273.
  6. Leon, S., & Pizzimenti, J. (2017). Be a Hero to Your HSVK Patients. Review of Optometry-Leadership in clinical care. Retrieved from https://www.reviewofoptometry.com/article/ro0717-be-a-hero-to-your-hsvk-patients2
  7. Institut national d’excellence en santé et en services sociaux. (2018). Herpes Simplex Eye Disease. INESSS Guides. Retrieved from https://www.inesss.qc.ca/fileadmin/doc/INESSS/Outils/GUO/Herpes/Guide_HerpesSimplex_web_EN_VF.pdf

 

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