This article is more than 5 years old. Information may no longer be current.
Neonate presents with irritation, redness in right eye
The patient and mother had an uncomplicated pregnancy. At day 11 of life, the patient was admitted for a fever of 102°F and a red right eye.
A 6-week-old girl was referred to the New England Eye Center for a chronically red right eye. The mother’s pregnancy was uncomplicated with no signs or symptoms of infection. The medical records indicated she was negative for GBS, gonorrhea, chlamydia, hepatitis B and VDRL. She had no evidence of genital ulcers.
On day 11 of life, the patient presented to an outside hospital with a fever of 102°F and a red, irritated right eye. A lumbar puncture showed elevated white blood cell count with normal protein levels. The patient was treated for suspected viral meningitis. The patient was admitted and treated with IV ampicillin, cefotaxime and acyclovir for 48 hours, at which time she was discharged. Blood and cerebrospinal fluid cultures were negative after 48 hours. At the time of discharge, the patient continued to have a red right eye and was given erythromycin ophthalmic ointment.
| Shazia Ahmed | My Hanh T. Nguyen |
As an outpatient, the right eye remained red, and the patient was subsequently referred to an ophthalmologist who started her on polymyxin and trifluridine drops for the next 2 weeks. The redness remained stable, at which point the patient was referred to New England Eye Center’s cornea service for further care.
Ocular, family, medical and surgical histories were noncontributory. The patient had no known drug allergies.
Examination
The patient demonstrated a good blink reflex to light in both eyes. The pupils appeared equally round and reactive to light. Extraocular movements were grossly intact.
External examination revealed mild right upper-lid swelling. Portable slit lamp examination revealed trace conjunctival injection extending 360°. Furthermore, the right eye had a vascular pannus located superotemporally near the limbus. The right cornea had a stromal infiltrate located between 9 and 1 o’clock with a large overlying epithelial defect (Figure). Both anterior chambers were deep and without hypopyon. The dilated fundus exam in both eyes demonstrated a flat, attached retina and was within normal limits.
|
Image: Chaturvedi V, Wu HK |
What is your diagnosis?
Neonatal red eye
The differential diagnosis for a neonatal red eye, as it originally presented at day 11 of life, is a classic one. The simplest way to think about the different etiologic agents is by time of onset. Chemical keratoconjunctivitis presents within the first 36 hours of life. It is typically caused by silver nitrate, which was originally used for prophylaxis against infectious keratoconjunctivitis. Bacterial causes usually present between 2 to 5 days of life. The most notable bacterial agent is Neisseria gonorrhoeae, which can develop into a rapidly malignant keratoconjunctivitis with corneal ulceration and perforation. Chlamydial conjunctivitis, the most common cause of neonatal conjunctivitis, usually presents sometime between the first and second week. The signs and symptoms of Chlamydial conjunctivitis are typically mild to moderate. Finally, herpes simplex virus (HSV) type 1 or type 2 presents anytime within the first 2 weeks of life.
The patient had been treated with topical antibiotics and topical antivirals. The clinical examination revealed large corneal ulcerations with no identifiable terminal dendrites consistent with herpetic infection. Further investigation of medical records from the inpatient hospitalization revealed positive spinal fluid results for herpes simplex type 1 DNA on PCR. Combining the clinical examination findings with the cerebrospinal fluid findings led to a diagnosis of a herpes simplex geographic ulcer with disciform stromal inflammation and a regional limbitis. The patient was started on acyclovir 200 mg three times a day, topical moxifloxacin ophthalmic solution every 2 hours to the right eye and topical prednisolone 1% ophthalmic solution four times a day to the right eye.
Corneal cultures were obtained. Bacterial and fungal cultures showed no growth while the viral cultures were positive for HSV type 2. The presence of HSV type 1 DNA in the cerebrospinal fluid and HSV 2 in the cornea most likely represented coincident co-infection of two separate viruses at two different locations. Once the bacterial cultures were negative, the topical moxifloxacin was discontinued.
The patient remained on the oral acyclovir and prednisolone with excellent results. The epithelial defect and overlying vascular pannus decreased in size on day 2 of follow-up. The prednisolone was tapered over time, and the patient’s large stromal ulcer began to decrease in size, resulting in a small peripheral scar. Ultimately, the patient was lost to follow-up as care was changed secondary to insurance reasons.
Discussion
Herpes simplex is a double-stranded DNA virus that is spread by direct contact. The incidence of herpes simplex keratoconjunctivitis is about 2,000 cases per year. About 80% of the ocular infections are caused by HSV type 2, while the remainder are caused by type 1.
Most of the infections occur at the time of vaginal delivery (although cases of cesarean section have been described) when the neonate passes through a vaginal canal that has active viral infection. Despite this, there are cases of postnatal transmission (about 10%).
Roughly 70% of documented neonatal HSV ocular infections are secondary to asymptomatic infections in the mother. In these cases, the mother either has a primary infection with no symptoms or a low-grade recurrent infection. In either case, the mother typically sheds the virus from the cervix, enabling it to be passed onto the neonate at the time of delivery.
HSV can create significant pathology at all levels of the human cornea. Our patient had significant disease taking place at the epithelial and stromal levels. The pathogenesis of epithelial disease results from active viral infection and resultant replication, while the stromal disease caused by HSV stems from an inflammatory reaction to viral antigens. With this knowledge at hand, the ophthalmologist can begin to determine how to combat the patient’s disease state by using antiviral therapy for the active infectious component and steroids for the inflammatory component.
The large Herpetic Eye Disease Study (HEDS) provides an excellent foundation when looking at HSV infection and management. The study came to several conclusions. Topical steroids (prednisolone) decreased stromal inflammation and shortened the duration of stromal keratitis when given in conjunction with topical antiviral therapy. Further, it found that oral acyclovir decreased the risk of recurrent ocular disease by 50%.
However, the ophthalmologist will run into difficulty when applying the results of HEDS to our particular patient. First, all of the patients in the study were older than 12 years of age. Second, when looking at the effects of treatment against stromal keratitis, none of the patients had any active epithelial keratitis. Third, if epithelial defects were present, patients were eliminated if the defects were larger that 1 mm in diameter. Although HEDS gives a strong foundation in HSV management, it is limited in its use in the neonatal population and in patients with coexistent epithelial and stromal disease.
Schwartz and Holland looked at seven eyes of seven patients between the ages of 6 weeks and 5 years who presented with combined stromal and epithelial HSV keratoconjunctivitis. All the patients received oral acyclovir (200 mg/5 cc) three times daily and topical steroids for their stromal disease. With this regimen, all patients had resolution of their epithelial keratitis and no adverse reactions to oral acyclovir. Although stromal disease remained with patients, it was controlled with long-term steroid use. The researchers concluded that oral acyclovir was an effective treatment against epithelial keratitis as well as an effective prophylaxis for patients with stromal disease while taking topical steroids.
This case highlights the issues surrounding the diagnosis, treatment and management of HSV keratitis in the neonatal population. Our patient had HSV manifestations at the stromal and epithelial layer. Each of these pathologies needed treatment. The combination of oral acyclovir along with topical steroids appeared to be an effective treatment for this particular presentation.
For more information:
- Vivek Chaturvedi, MD, and Helen K. Wu, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; Web site: www.neec.com.
- Edited by Shazia Ahmed, MD, and My Hanh T. Nguyen, MD. Drs. Ahmed and Nguyen can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; Web site: www.neec.com. Drs. Ahmed and Nguyen have no direct financial interest in the products mentioned in this article, nor are they paid consultants for any companies mentioned.
References:
- Brown ZA, Benedetti J, et al. Neonatal herpes simplex virus infection in relation to asymptomatic maternal infection at the time of labor. N Engl J Med. 1991;324(18):1247-1252.
- Collum LM, Akhtar J, McGettrick P. Oral acyclovir in herpetic keratitis. Trans Ophthalmol Soc U K. 1985;104 (Pt 6):629-632.
- Corey L, Whitley RJ, Stone EF, Mohan K. Difference between herpes simplex virus type 1 and type 2 neonatal encephalitis in neurological outcome. Lancet. 1988;1(8575-6):1-4.
- Fleming DT, McQuillan GM, et al. Herpes simplex virus type 2 in the United States, 1976 to 1994. N Engl J Med. 1997;337(16):1105-1111.
- Nahmias AJ, Visintine AM, Caldwell DR, Wilson LA. Eye infections with herpes simplex viruses in neonates. Surv Ophthalmol. 1976;21(2):100-105.
- Schwartz GS, Holland EJ. Oral acyclovir for the management of herpes simplex virus keratitis in children. Ophthalmology. 2000;107(2):278-282.
- Sudesh S, Laibson PR. The impact of the herpetic eye disease studies on the management of herpes simplex virus ocular infections. Curr Opin Ophthalmol. 1999;10(4):230-233.
- Whitley RJ. Herpes simplex virus infection. In: Remington JS, Klein JO, eds. Infectious Diseases of the Foetus and Newborn Infant. 3rd ed. Philadelphia: WB Saunders; 1990:282-305.
- Wilhelmus KR, Gee L, et al. Herpetic Eye Disease Study. A controlled trial of topical corticosteroids for herpes simplex stromal keratitis. Ophthalmology. 1994;101(12):1883-1895; discussion 1895-1896.