Maria Kelley, MD

Five-year-old girl with redness and light sensitivity of the right eye of 2 days' duration. She denied any significant pain or decreased vision. She initially presented to an urgent care clinic, where application of polymyxin B/trimethoprim eye drops 4 times a day was prescribed. Her symptoms had persisted despite this treatment. The mother was concerned because her daughter had kept the right eye closed since she awoke that morning. She also had noticed minimal clear discharge from the eye.

Otherwise healthy child with no chronic medical conditions. She was given no medications other than the eye drops. She had no fevers, headaches, or difficulty in swallowing; 
 no history of recent travel or travel abroad; and no pets. Family was unaware of any other children (in day care or neighborhood) with “pink eye.”

Alert, active child in slight distress related to her right eye. She was afebrile. Vital signs appropriate for her age. She had no preauricular lymph node enlargement. Systemic examination findings within normal limits.

Visual acuity 20/40 in right eye, 20/30 in left eye. Pupils equal and reactive to light, eyes aligned, and extraocular movements full. Right lower lid slightly edematous and erythematous; no vesicular or pustular lesions noted on the lid margin or periorbital skin. Conjunctiva significantly injected with diffuse tiny gelatinous bumps (

). Corneal light reflex slightly irregular in some areas; cornea otherwise clear. Anterior chamber and red reflex also clear. Left eye completely normal.

Right eye viewed by Wood lamp after application of fluorescein dye as shown (

Wood lamp examination after fluorescein dye instillation revealed small branching lesions on both the cornea and conjunctiva, representative of herpes simplex conjunctivitis and keratitis. The girl was referred to ophthalmology. A conjunctival swab sent for herpes simplex virus (HSV) testing by fluorescent antibody revealed HSV type 1. This result was subsequently confirmed by viral culture.

HSV has been identified as the causative agent in as many as 21% of cases of acute follicular conjunctivitis.

 Herpes simplex conjunctivitis can result from primary infection or reactivation of latent HSV infection in the trigeminal ganglion.

Diagnosis of herpes simplex conjunctivitis is usually clinical, based on the characteristic appearance of significantly injected conjunctiva with diffuse tiny gelatinous bumps, which indicate a follicular reaction. About 90% of cases of conjunctivitis caused by HSV are unilateral.

 Primary herpetic conjunctivitis or keratoconjunctivitis is often associated with blepharitis and tender preauricular lymphadenopathy, although this sign is usually absent in recurrent disease.

The conjunctivitis may be associated with keratitis, which is characterized by branching dendrites on the cornea and conjunctiva that appear to have terminal bulbs on close examination. The dendrites stain with fluorescein as well as with Rose Bengal, a vital dye that stains HSV-infected cells at the periphery of the lesions. In cases without corneal involvement, swabbing the conjunctiva for viral culture can confirm the diagnosis. Serology is not useful in diagnosis because the sensitivity and specificity are low for this test.

Herpetic conjunctivitis and even keratitis often resolve spontaneously. However, in untreated cases or with repeated recurrences, keratitis often leaves residual scarring in the shape of a “ghost dendrite” that may affect vision if in the visual axis. Therefore, treatment is advised in all patients with herpes keratoconjunctivitis. Application of topical 1% trifluridine eye drops every 2 hours while awake is the standard therapy for herpetic keratitis. Oral acyclovir or valacyclovir may be used in patients who may not cooperate with topical administration. Recently, a new topical formulation of 0.15% ganciclovir ophthalmic gel, applied 5 times daily, has been approved for use in the United States and may make topical therapy more convenient. Gentle wiping of the corneal lesion can hasten resolution of keratitis; this is because the infected cells adhere poorly and debride easily, while the surrounding normal cells are unaffected.

 Prophylactic therapy with an oral antiviral is recommended for patients with recurrent herpetic eye disease because studies have shown that it decreases the risk of recurrence by 50%.

This girl was treated with trifluridine eye drops as well as oral acyclovir, and the corneal lesion was debrided with a cotton swab. At follow-up a week later, her symptoms had completely resolved. She had no residual corneal scarring, and her vision was 20/30 in both eyes with Allen cards. She continued treatment with the topical and oral medications for a total of 2 weeks. The mother was informed of the possibility of recurrence and was instructed to bring the child to the ophthalmologist immediately if she notices any eye redness. Prophylactic treatment with oral acyclovir was also offered, but this was deferred.

1. Wishart PK, James C, Wishart MS, Darougar S. Prevalence of acute conjunctivitis caused by chlamydia, adenovirus, and herpes simplex virus in an ophthalmic casualty department. 

2. Uchio E, Takeuchi S, Itoh N, et al. Clinical and epidemiological features of acute follicular conjunctivitis with special reference to that caused by herpes simplex virus type 1. 

3. Wilhelmus KR. Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis. 

4. Young RC, Hodge DO, Liesegang TJ, Baratz KH. Incidence, recurrence, and outcomes of herpes simplex virus eye disease in Olmsted County, Minnesota, 1976-2007: the effect of oral antiviral prophylaxis. 

Articles

Five-year-old girl with redness and light sensitivity of the right eye of 2 days' duration. She denied any significant pain or decreased vision. She initially presented to an urgent care clinic, where application of polymyxin B/trimethoprim eye drops 4 times a day was prescribed.

Young Girl With “Bumpy” Red Eye


 A 6-month-old boy with different colored eyes since   birth. The parents are concerned that the eye anomaly   may be associated with an underlying condition after   reading about eye disorders online. They think the color   of the eyes may have darkened slightly but have not noticed   an unequal appearance to the pupils or drooping of   either upper eyelid. No family members, including an   older brother, have similar eye discoloration. There is no   history of consanguinity. Otherwise healthy infant with   normal stools and no chronic diarrhea. Prenatal and   postnatal histories uneventful, developmental milestones   appropriate. No history of prenatal maternal infections or   perinatal trauma. Results of newborn hearing screen normal,   no hearing problems subsequently reported.


 Happy infant with stable vital signs. Physical findings   and growth parameters essentially within normal   limits for age. Ocular examination reveals normal lids   and lashes, with no ptosis, bruising, or port-wine stains.   Conjunctiva is white, with no corkscrew vessels. Cornea   is clear; anterior chamber is deep and appears quiet.   Right iris has dark brown pigmentation except for the   area between the 6 and 8 o’clock position, which is bluegray   and sharply demarcated. Iris architecture appears   normal, although the iris crypts are less visible in the   darker brown area of the right eye on close examination.   Left iris is blue-gray at the periphery and hazelbrown   centrally near the pupil. Remaining ocular findings   normal. Extraocular movements intact in all directions.   Both pupils dilate equally in the dark and constrict   equally in response to light.

Heterochromia of the iris is relatively uncommon and may be congenital or acquired. This child has congenital heterochromia, which is usually inherited as an autosomal dominant trait but may be seen in mosaicism, or rarely in chimerism. In isolated cases, it has no medical significance, and otherwise healthy patients can be reassured of its benign prognosis.


 Heterochromia iridis can be described as complete   or partial.1 Partial heterochromia may be further classified   as central or sectoral. In complete heterochromia,   one eye is lighter than the other because of a decreased   number of pigment granules in the iris stroma. In partial   heterochromia, one portion of the iris is a different   color from the rest of the iris. In central heterochromia   (this patient’s left eye), the peripheral portion of the iris   is lightly pigmented while the central area around the   pupil is darker. In sectoral heterochromia (this patient’s   right eye), one section of the iris is darker than the rest.

  
 Although heterochromia is normally a benign finding   on physical examination, it may be associated with   multiple congenital syndromes and acquired diseases.

  Unilateral heterochromia that manifests as lighter   pigmentation of one iris is associated with Waardenburg   syndrome and Parry-Romberg syndrome and less commonly   with Hirschsprung disease. Waardenburg syndrome,   an autosomal dominant inherited disorder, is   characterized by a white forelock, cutaneous hypopigmentation,   wide-set eyes (telecanthus), prominence of   the nasal root, and hearing loss. Parry-Romberg syndrome   is a craniofacial disorder characterized by slow   development of hemifacial atrophy as well as seizures   and severe facial pain. Hirshsprung disease, or congenital   aganglionic megacolon, results from an absence of   ganglion cells in the submucosal (Meissner) and the   myenteric (Auerbach) plexuses in 1 or more segments   of the colon. The aganglionic segment is limited to the   rectosigmoid colon in 75% of patients and the entire   colon in 10% of cases. In short-segment Hirshsprung disease,   only the region of the internal sphincter is affected.

Unilateral heterochromia that manifests as darker   pigmentation of the iris is associated with ocular or oculodermal   melanosis and Sturge-Weber syndrome. Ocular   melanosis is caused by an increase of melanocytes in   the iris and choroid. When the skin supplied by the ophthalmic   and maxillary divisions of the trigeminal nerve   is also involved, the condition is called oculodermal   melanosis, or nevus of Ota. Ocular melanosis may cause   glaucoma and is associated with a higher than normal   risk of malignant transformation to melanoma. Sturge-   Weber syndrome is a phakomatosis that is characterized   by a port-wine stain of the face (generally in the ophthalmic   division of the trigeminal nerve), glaucoma,   seizures, mental retardation, intracranial calcifications   that are typically paired (often referred to as trolley   tracks), and ipsilateral leptomeningeal angiomatosis.

Heterochromia as a manifestation of Horner syndrome   is a result of interrupted sympathetic innervation   of the eye.

Patients with Horner syndrome have mild to   moderate ptosis, slight elevation of the lower lid, miosis,   and dilation lag with removal of light stimuli-regardless   of the level of sympathetic interruption. The affected iris   is generally lighter because of the role sympathetics play   in melanin production in the superficial stroma. In children   who have Horner syndrome with heterochromia,   especially those with increasing iris hypopigmentation,   imaging must be performed to rule out neuroblastoma.

Acquired heterochromia may be caused by injury   (eg, a retained iron-containing foreign body can cause   siderosis and darkening of the iris), inflammation   (Fuchs heterochromic iridocyclitis),

 medications (certain   glaucoma medications, specifically prostaglandin   analogues),


 This boy’s parents were most concerned about   Horner syndrome, of all the associated conditions, because   they thought his iris may have changed color.   The parents were reassured that the child’s heterochromia   was a benign variation in iris color that was   probably inherited. On examination of the father’s eyes,   the central aspect of his iris appeared darker than the   periphery, consistent with central heterochromia.

 Swann PG. Heterochromia signs & symptoms. 

 Renard D, Jeanjean L, Labauge P. Heterochromia iridis in congenital Horner’s  syndrome. 

 Beynat J, Soichot P, Bidot S, et al. Iris heterochromia in acquired Horner’s  syndrome [in French]. 

 Jones NP. Fuchs’ Heterochromic uveitis: a reappraisal of the clinical spectrum.  

Camras CB. Comparison of latanoprost and timolol in patients with ocular  hypertension and glaucoma: a six-month masked, multicenter trial in the United  States. The United States Latanoprost Study Group. 

 Skalicky SE, Giblin M, Conway RM. Diffuse iris melanoma: report of a case  with review of the literature. Clin Ophthalmol. 2007;1:339-342.  8. Demirci H, Shields CL, Shields JA, et al. Diffuse iris melanoma: a report of  25 cases. 

A 6-month-old boy with different colored eyes since birth. The parents are concerned that the eye anomaly may be associated with an underlying condition after reading about eye disorders online.

Young Boy With Different Colored Eyes

A 16-year-old boy presented for evaluation of his worsening behavior at school. He was very hyperactive and had difficulty in paying attention. He had always required help with reading and language. Maternal pregnancy and birth history were unremarkable.

During the physical examination, the patient was noted to have 8 hyperpigmented macules ranging from 2 to 8 cm with smooth margins, 7 or 8 flesh-colored, nontender papules, and 3 nodules on the trunk (

). His mother had numerous similar lesions on her trunk (

). Neither son nor mother had any changes in vision, heart murmur, or bony deformity. A diagnosis of neurofibromatosis had been suspected by a previous physician but had not been confirmed.

Neurofibromatosis type I, first described by von Recklinghausen in 1882, is one of the most common autosomal dominant neurocutaneous conditions. The estimated incidence is 1 in 2500 to 3000 persons, independent of ethnicity, race, and gender.

Formal diagnostic criteria were established by the Health Consensus Development Conference in 1987. Currently, the diagnosis is made when 2 or more of the following clinical features are present

Neurocognitive deficits, including gross and fine motor delays, visuospatial and language disorders, attention-deficit/hyperactivity disorder, autism spectrum disorder, and behavior and psychosocial issues, are very common in patients with neurofibromatosis type I. All children with neurofibromatosis type I should have a developmental and neuropsychological assessment before school entry for educational planning.

Associated cardiovascular issues include congenital heart disease, vasculopathy (renal artery stenosis, coronary heart disease, cerebrovascular disease, arteriovenous malformations), and hypertension. Annual blood pressure screening and cardiovascular examination are recommended.

Scoliosis is present in 10% to 25% of patients and, depending on severity, may be treated by braces, corrective surgery, or early spinal fusion.

 Short stature is seen in about 15% of patients.

Consultation with cardiac, orthopedic, and ophthalmological specialists may be indicated to rule out or manage conditions associated with neurofibromatosis.

This patient was enrolled in a behavior modification program. He was also placed in the individualized education program at school for children with learning disabilities. At last checkup, he was making good progress.

 Williams VC, Lucas J, Babcock MA, et al. Neurofibromatosis type 1 revisited. 

 Ferner RE, Huson SM, Thomas N, et al. Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. 

 Tsirikos AI, Saifuddin A, Noordeen MH. Spinal deformity in neurofibromatosis type-1: diagnosis and treatment. 

 Alwan S, Armstrong L, Joe H, et al. Associations of osseous abnormalities in neurofibromatosis 1. 

Maria Kelley, MD

Articles

Young Girl With “Bumpy” Red Eye

Young Boy With Different Colored Eyes

Developmental Delay in a Teen With Neurofibromatosis Type I