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Introduction – Background Information
Herpes simplex keratitis is an infection caused by the herpes simplex virus (HSV). It is a condition that can affect multiple structures of the eye including the eyelids, conjunctiva, and cornea. eyes. Approximately 90% of the population is exposed to HSV, mostly during their childhood.1 It affects males and females equally. It is extremely contagious and is transmitted by direct contact with an active lesion. The initial presentation is typically blepharoconjunctivitis and keratitis. Pain, tenderness, injection, photophobia, serous discharge, and dendrites are the most common symptoms. More severe cases can lead to corneal scarring, loss of vision, and even blindness.

Case Report
A 62 year old Caucasian female presented as a walk in on June 21, 2018 with a complaint of red and watery eyes. She states that this started about three days ago in her left eye and is now affecting her right eye. When she woke up this morning, her left eye was crusted and she was light sensitive. Her last eye exam was February 2017. Her ocular history includes dry eye syndrome with mild meibomian gland dysfunction, bilateral inverted lower puncta, allergic conjunctivitis, mild transillumination defects in both eyes, trace nuclear sclerosis, presbyopia, retinal vascular attenuation, and LASIK on her right eye for monovision correction (left eye dominant). Family ocular history was negative for glaucoma and macular degeneration. Her medical history was negative for diabetes and hypertension. Family medical history was positive for diabetes (mother, father, and siblings) and hypertension (father and brother). Social history includes alcohol use on occasion and smoking cessation since June 2012. She was using Restasis and Zaditor.

Her uncorrected distance visual acuity was 20/80 (PH: 20/25) OD and 20/25 OS. Pupils were equal, round, and reactive to light; no evidence of an afferent pupillary defect. Confrontational visual fields were full to finger count OD, OS. Extraocular muscle testing showed no restriction, pain, or diplopia. One drop of Flucaine was instilled in both eyes in order to measure intraocular pressure. Goldmann tonometry measured 16 mmHg OD and 18 mmHg OS at 7:32 AM. Slit lamp exam showed normal lids, lashes, and adnexa without debris. The right conjunctiva had trace injection, while the left had 2+ diffuse injection with mild chemosis. The right cornea had a LASIK scar, while the left had no opacities. Both anterior chambers were deep and quiet with angles measured using the Van Herrick method appearing to be 4×4. Both irides were flat and intact with no signs of neovascularization. Evaluation of the lens revealed trace nuclear sclerosis in both eyes. Dilation was not performed during this visit.

Differential diagnoses to be considered include the following:
o Viral conjunctivitis
o Bacterial conjunctivitis
o Allergic conjunctivitis
o Superior limbic keratoconjunctivitis
• Viral conjunctivitis is most common and is highly contagious. It typically starts in one eye and involves the other eye several days later. It is often associated with watery discharge and redness.2
• Bacterial conjunctivitis more common in children and can be unilateral or bilateral. It usually presents with a mucous discharge, rather than serous.
• Allergic conjunctivitis is not contagious and can be caused by numerous things. It is more common in patients with other allergic conditions including asthma and eczema.
• Superior limbic keratoconjunctivitis is due to friction. This usually presents with foreign body sensation and typically affects middle aged women.

The appearance of the left eye and symptoms experienced by the patient suggests viral conjunctivitis based on the following: 2+ diffuse injection and mild chemosis of the conjunctiva, serous discharge, and ocular involvement in one eye followed by involvement of the fellow eye several days later. She was educated on the highly contagious and self-limiting nature of the infection. She was advised to wash all towels and bedsheets to prevent spreading and reinfection. The patient was started on Pred Forte 1% four times a day in the left eye and was scheduled for an anterior segment follow up in one week. She was to continue using Restasis and Zaditor as needed. Her cataracts were not visually significant and would continue to be monitored.

Follow Up #1
The patient returned on June 25, 2018 for an anterior segment check and was seen by another doctor within the clinic. She stated that her symptoms were the same. Both eyes were still red, watery, and light sensitive, with her left eye being worse. She reported compliance with her medication schedule.

Her uncorrected visual acuity was 20/60+ (PH: 20/25) OD and 20/20 OS. All entrance exams remained stable. One drop of Flucaine was instilled in both eyes. Goldmann tonometry measured 16 mmHg OD and 17 mmHg OS at 8:12 AM. Slit lamp exam was positive for papillae OU and nasal crust OS. The right conjunctiva had trace injection, while the left had 2+ nasal injection with mild chemosis. All other findings were consistent with the previous visit.

Differential diagnoses to be considered include the following:
o Giant papillary conjunctivitis
o Angular blepharoconjunctivitis
o Atopic keratoconjunctivitis
• Giant papillary conjunctivitis is a non-infectious complication common in patients with contact lens use and is due to friction or protein deposits on the lens. Symptoms include itching and mucous discharge.3
• Angular blepharoconjunctivitis can be caused by Moraxella or Staphylococcus species. This infection causes conjunctival hyperemia in the lateral or medial canthal region and ocular irritation.
• Atopic keratoconjunctivitis can present with redness, photophobia, watery discharge, and papillae. It is most common in patients with a history of atopic conditions.

The patient’s ocular exam and history suggest angular blepharoconjunctivitis based on the following findings: papillae in both eyes, nasal crust OS, and 2+ nasal injection with mild chemosis OS. She was prescribed TobraDex suspension three times a day in both eyes and Erythromycin ointment in both eyes every night. Zaditor and Restasis could be used as needed. A follow up appointment was scheduled for three days if she did not experience an improvement in her symptoms. Otherwise, she was to discontinue TobraDex and Erythromycin after seven days.

Follow Up #2
The patient presented to the clinic on July 10, 2018 as a walk in and was seen by the same doctor as the previous follow up. She had complaints of red, irritated, watery, and photophobic left eye. She states that her symptoms are similar to the previous visit, but without crusting in the corners of her eye. She experiences intermittent pain that lasts for a few seconds and rates it as 7/10. Her symptoms seem to come and go.

Her uncorrected visual acuity was 20/50+ (PH: 20/25) OD and 20/20 OS. All entrance exams remained stable. One drop of Flucaine was instilled in both eyes. Goldmann tonometry measured 16 mmHg OD and 16 mmHg OS at 10:38 AM. Slit lamp exam was positive for papillae and trace debris OU. The right conjunctiva had trace injection, while the left had 2+ nasal injection with mild chemosis. The right cornea had a LASIK scar, while the left had six scattered early stellate dendrites inferior and temporally. All other findings were consistent with the previous visit.

Differential diagnoses to be considered include the following:
o Herpes simplex keratitis
o Herpes zoster ophthalmicus
• Herpes simplex keratitis typically results from a reactivation of the latent infection in the trigeminal ganglion. There are many triggers including stress, sun exposure, and suppression of the immune system. This infection typically presents with pain, redness, serous discharge, decreased vision, and photophobia. During the primary exposure, blepharitis and/or conjunctivitis are typically seen. The most common presentation are dendritic ulcers. The edges of the dendrites will still well with rose bengal, while the center ulcer stains well with sodium fluorescein. In more severe cases, it can invade into the corneal stroma and endothelium.
• Herpes zoster ophthalmicus is caused by the Varicella zoster virus and primarily affects elderly and immunocompromised patients. The typical presentation is unilateral involvement and follows the affected dermatomes. Corneal involvement will begin with small, stellate lesions that progress into pseudodendrites, which do not have terminal bulbs, and appear to be “stuck on”. Rose bengal will stain the entire lesion and sodium fluorescein will not stain the lesions. Patients with Hutchinson’s sign have an increased risk for ocular involvement.

The following symptoms and exam findings suggest herpes simplex epithelial keratitis: early stellate dendrites that stain well with sodium fluorescein, pain, redness, serous discharge, and photophobia. She was educated on the nature of the infection and recurrence severities. She is aware of the risk for a recurrent infection due to Restasis and previous steroid usage. Ganciclovir five times a day in the left eye and Acyclovir 400 mg by mouth five times a day were prescribed. Patient was to discontinue use of TobraDex, Erythromycin, and Restasis. An over the counter preservative free artificial tear was recommended in place of Restasis. Zaditor was to be used as needed. A follow up appointment was scheduled for two days, or sooner if symptoms worsen.

Follow Up #3
The patient returned to clinic on July 13, 2018 for an anterior segment follow up and was seen by another doctor within the practice. She stated that her eyes were feeling much better and that the redness is mostly gone. They are still watering, but not as much and she does not feel photophobic. She reports compliance with the medication schedule and noted that she is also using Lumify in both eyes.

Her uncorrected visual acuity was 20/50 (PH: 20/25) OD and 20/20 OS. All entrance exams remained stable. One drop of Flucaine was instilled in both eyes. Goldmann tonometry measured 16 mmHg OD and 16 mmHg OS at 2:14 PM. Slit lamp exam was positive for mild papillae and trace debris OU. She had trace injection OU. The right cornea had a LASIK scar, while the left had mild SPK. All other findings were consistent with the previous visit. Her infection was mostly resolved at this time.

She was instructed to continue the Ganciclovir five times a day in the left eye and Acyclovir 400 mg po five times a day until finished. She was advised to return to the clinic if she experiences similar symptoms and to continue using preservative free artificial tears as needed.

Discussion
Herpes Simplex Virus Type one is the most common cause affecting the eyes. After the initial infection, the virus lies dormant in the trigeminal ganglia and can be reactivated by various things such as stress, sun/UV exposure, fever, trauma, and medications.1 It is the leading cause of infectious blindness in the United States.

During the initial infection, blepharoconjunctivitis and keratitis are the most common manifestations. Patients will experience pain, foreign body sensation, itching, redness, and serous discharge. Treatment of blepharoconjunctivitis includes supportive therapy such as artificial tears, warm and cool compresses. If the patient has keratitis, Cyclogyl 1% can be used twice a day in the affected eye, as well as artificial tears, topical antivirals (Viroptic nine times a day or Zirgan five times a day), oral antivirals (Acyclovir 400 mg po five times a day for one to two weeks or Valacyclovir 500 mg three times a day for one to two weeks), or debridement.1 No steroids should be used in the case of a keratitis. Using a steroid can increase the severity of the condition and lead to geographic ulcers, seen in figure 1. True dendrites, as seen in figure 2, will be seen with corneal involvement. These lesions will stain centrally with sodium fluorescein, while the edges will stain well with rose bengal. Recurrent episodes can be more severe and affect deeper structures which can cause complications such as recurrent corneal erosions, interstitial keratitis, disciform keratitis, scarring, and neovascularization.

Figure 1 Figure 2

Stromal disease can be categorized as interstitial keratitis (necrotizing) or disciform (non-necrotizing) and lead to scarring and neovascularization. Interstitial keratitis is rare and due to the active replication of the virus within the stroma. White, diffuse corneal stromal infiltrates will be present, as well as stromal inflammation, and thinning. Uveitis and hypopyon can also be manifested. Disciform keratitis involves the corneal endothelium and can occur in patients without a history of herpes simplex keratitis. Some signs and symptoms include round area of stromal edema, increased IOP and Descemet folds.

For the majority of cases, ocular manifestations never occur. If a patient experiences one occurrence, they are at a 40% risk of recurrence. Shorter duration between episodes and more severe first episodes also put patients at an increased risk for recurrence. The prognosis for Herpes Simplex Keratitis is generally good. 90% of patients will see 20/40 or better after twelve years and 2% will see 20/100 or worse after twelve years.

Treatment from our patient’s initial visits and her Restasis may have suppressed her immune system enough for the herpes simplex keratitis to manifest. After asking more in depth questions about the patients past medical history, it was confirmed that she has had cold sores in the past, which helped confirm our suspicions. Our patient had a very typical presentation of the condition including pain, corneal dendrites, and serous discharge. The standard of care was used to treat this infection which includes Ganciclovir five times a day for one week, oral Acyclovir five times a day for one week, and artificial tear use.

Conclusion – Summary/Take Away
This case demonstrates the typical presentation of the initial infection of herpes simplex virus involving the eye. This condition is typically diagnosed by clinical presentation, along with a detailed patient history. A culture can be taken, but is often unnecessary. Treatment options should include topical antivirals, oral antivirals, and artificial tears. Steroids should not be prescribed to patients with epithelial defects. Educating patients on the risk of recurrence is important so they are aware if they begin to experience similar symptoms in the future. These patients should then be monitored annually.

References
1. “What Is Herpes Keratitis?” American Academy of Ophthalmology, 25 Apr. 2018, www.aao.org/eye-health/diseases/herpes-keratitis.
2. “Healthy Contact Lens Wear and Care.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 27 Jan. 2015, www.cdc.gov/contactlenses/viral-keratitis.html.
3. “Giant Papillary Conjunctivitis: Stages, Treatment, and Remedies.” Healthline, Healthline Media, www.healthline.com/health/giant-papillary-conjunctivitis.
4. “Herpes Zoster Ophthalmicus.” American Academy of Ophthalmology, www.aao.org/focalpointssnippetdetail.aspx?id=8367b620-245c-4ebf-89e7-eca0c8d35aa3.

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