CASE STUDY

Conflicting Symptoms in Pediatric Patient

Patient's medical history offers few clues.

Mark T. Dunbar, O.D.

An eight-year-old Hispanic female presented with a two-year history of intermittent redness and itching in her left eye and similar, but milder symptoms in the fellow eye.

Her past social and medical history offered few clues: She reported a lifelong history of eczema, wasn't using any medications and had no known allergies. In addition, her family medical history was unremarkable.

Exam findings

On examination, the patient's uncorrected visual acuity measured 20/25 OD and 20/40 OS. At near, she was able to see J1 OU.

I was able to correct the patient to 20/20 OD with a -0.75 + 1.25 × 105. I was able to correct her to to 20/40 OS.

On retinoscopy, her reflex was dim and uninterpretable.

The patient's confrontation visual fields were full-to-careful finger counting OU.

Her extraocular motility testing was normal.

Stereo testing revealed the patient could see six out of nine circles.

Her pupils were equally round and reactive with no afferent pupillary defect.

Her anterior segment exam showed clear lid margins OU.

I noticed a 2+ follicular response in the lower fornix, which I perceived to be juvenile in nature. The upper tarsus showed 1+ papillae OU.

Figure 1: The inferior cornea of the right eye revealed fine punctate epithelial erosions and scattered subepithelial infiltrates.

Slit lamp exam revealed multiple, small corneal infiltrates scattered throughout the cornea, as well as fine punctate epithelial erosions (PEE), which were more prominent inferiorly (see figure 1).

I noted several small areas of pannus in this eye as well. No epithelial defects were present.

The patient's left eye revealed obvious subepithelial infiltrates of varying sizes as well more pronounced PEE and punctate epithelial keratitis (PEK) (see figure 2).

In addition, the patient's left eye had an area of corneal neovascularization inferior in two locations that encroached approximately 5mm to 6mm onto the cornea.

Of particular note: There was a large disciform area of corneal thinning in her central cornea associated with subepithelial and stroma haze.

A 3mm epithelial defect was present within the central haze, with an associated infiltrate.

The patient's anterior chamber was 4+ deep without cell or flare OU.

Her iris was flat without any mass or rubeosis, and her crystalline lens was clear. The patient's fundus exam was completely normal.

Diagnosis

Based on the clinical findings it was felt that she had a cornel ulcer in her left eye. What was more difficult to determine was the underlying etiology. Possible considerations included vernal keratoconjunctivitis (VKC), atopic keratoconjunctivitis (AKC) and even childhood ocular rosacea. She was seen by a dermatologist and we eventually settled on a diagnosis of atopic keratoconjunctivitis.

Discussion

Clearly this was not a straightforward diagnosis. Any of those in the above differential diagnosis list could be strong considerations for the underlying problem.

Atopic keratoconjunctivitis (AKC) is a bilateral chronic inflammation of the conjunctiva and lids associated with atopic dermatitis. A total of 3% of the population suffers from atopic dermatitis with 5% to 67.5% having ocular involvement.¹ The chief symptom of AKC, as it is with many of the allergic eye conditions, such as seasonal allergic conjunctivitis (SAC) and VKC, is itching.

The hallmark signs of the disease include scaling, flaking and dermatitis of the skin and lids.

In more severe cases, the eyelid changes can be very apparent, revealing a thick, leathery, lichenified appearance. Patients can also develop lateral canthal ulceration, skin cracking and loss of lashes. The bulbar conjunctiva may show only diffuse injection and chemosis, however, you can see papillae in the upper and lower fornix.

Interestingly, the papillae seen on the upper tarsus in AKC tend to be much smaller than that seen with VKC. In fact with AKC, the papillary hypertrophy is more prominent in the inferior conjunctival fornix than the upper tarsus.¹

Figure 2: The cornea of the patient's left eye revealed pronounced punctate epithelial erosions, punctate epithelial keratitis and numerous subepithelial infiltrates. Also present: An epithelial defect in the central cornea.

When loss of vision occurs, it's usually due to chronic punctate epithelial keratopatitis and corneal scarring. Patients can even develop decreased corneal sensitivity as well as persistent epithelial defects, ulceration, plaque formation, lipid infiltration and corneal neovascularization. In extreme cases, you may need to refer these patients for penetrating keratoplasty, however, the chronic disease state may result in continued ocular surface changes, which can lead to further surface irregularities and even graft failure.

Researchers believe that the pathophysiology of AKC is a result of a type I and type IV hypersensitivity reaction as well as the interplay of several complex immunological and inflammatory pathways.

One of the chief characteristics of all forms of ocular allergy is the presence of eosinophils, a key mediator for inflammation. Interestingly, researchers believe that loss of corneal sensitivity is an important barometer for disease progression. Even among corneal-ulcer patients, corneal sensitivity is further reduced compared with eyes that don't have a corneal ulcer. It's the loss of corneal sensitivity that strongly implies corneal epithelial and stromal disease and progression of the disease.^2-3

Distinguishing AKC from VKC is challenging given that each condition has similar features.

The age of onset for AKC is usually in the second through fifth decade, however, several reports show the age of onset as early as seven years old. The onset of VKC is typically prior to age 10. It's unusual to see VKC in patients older than age 20. VKC tends to appear earlier in males than in females, however in older patients it occurs equally between sexes.

The hallmark clinical findings in VKC include large "cobblestone papillae" under the upper tarsus that are associated with thick, ropy mucous strands. Patients can also develop limbal papillae that appear as areas of gelatinous thickening around the limbus. It's very unusual to see skin changes around the lids. VKC patients, like AKC patients, however, can suffer from other atopic conditions, such as eczema or asthma. VKC patients tend to develop shield ulcers, whereas AKC patients tend to develop persistent epithelial defects that can resemble shield ulcers, but differ in etiology.

Figure 3: The punctate epithelial erosions and scattered subepithelial infiltrates seen in the patient's right eye completely resolved after treatment.

Researchers believe shield ulcers develop from the release of mediators from the inflamed tarsal conjunctiva. These mediators on the cornea result in areas of punctate epithelial keratitis that can coalesce into epithelial erosions, and, finally, into round or oval shield ulcers that are located just superior to the visual axis¹.

Ocular rosacea typically manifests in adults. The medical literature, however, reports ocular rosacea occurring in the pediatric population.^4-5 In fact, one study reported 20 patients (ages 22 months to 17 years) who presented during childhood with corneal pathology, lid-margin disease and skin changes consistent with ocular rosacea.⁴

Another study reported four cases of childhood rosacea occurring in children between the ages of four and 12. All were females with bilateral disease.⁵ Clinical findings included meibomitis, blepharitis, conjunctival hyperemia and punctuate epitheliopathy in all cases. Limbal vascularization with subepithelial or stromal infiltrates was present in three cases (75%).

Figure 4: Note the resolution of the subepithelial infiltrates and complete re-epithelialization of the cornea ulcer. Also, note thinning of the cornea in the area of the scar.

Management

Interestingly, our patient didn't have any of the skin changes typically seen in patients with AKC. She didn't have the cobblestone papillae or thick, ropy discharge typically seen in VKC either. I felt that the patient's clinical history and findings were more consistent with AKC, but I wasn't absolutely certain. So, I obtained a consultation with a corneal specialist. Together, we decided to employ a treatment plan that was similar if not exactly the same had I determined that the patient had VKC.

In the meantime, the patient reported she had an existing appointment to see a dermatologist in two weeks. I asked the patient to keep the appointment and provided her with a note to give to the dermatologist, which described the eye findings in addition to what my considerations were with regard to the treatment.

Given that most of the corneal findings in both eyes were immune mediated and that an inflammatory component was clearly contributing to this patient's disease state, we started her on Restasis (cyclosporine 0.05%), a prescription therapy for dry eye, t.i.d., OU. This drop reduces inflammation by selectively supressing T-cells. I also prescribed a fourth-generation fluoroquinolone q.i.d. (gatifloxacin 0.3%) OS for coverage of any potential pathogens.

Ideally, I would have pre-scribed topical steroids to control the inflammation as well as modulate the autoimmune nature of her condition, but the presence of a corneal ulcer in her left eye obviously precluded their use. For this reason, Restasis was prescribed at a dose of t.i.d. compared with the traditional b.i.d. dosing.

Figure 5: The optic section of this patient's left eye reveals re-epithelialization and thinning of the central cornea.

Follow-up and outcome

The patient returned three weeks later. Clinical evaluation revealed marked improvement in her symptoms as well as her appearance (see figures 3 through 5), and she reported that both the redness and itching were gone.

Visual acuity OS improved from 20/40 to 20/25 with -1.25 + 0.50 × 015. Evaluation of her anterior segment OD revealed an almost complete resolution of the subepithelial infiltrates. A few small areas of corneal opacification remained, but there was no NaFl staining. The epithelial defect OS completely healed despite thinning over the affected area of approximately 20%. Significant subepithelial and anterior stromal scaring is evident over the affected area. Corneal neovascularization appeared less active than at the initial exam.

We recommended she continue with the dry-eye drop t.i.d., OU. We added a corticosteroid t.i.d. to minimize the formation of the scar. OM

1. Barney NP. Vernal and Atopic Keratoconjunctivitis. In: Cornea. Editors Jay Krachmer, Mark Mannis, Edward Holland. Elsevier 2004, Vol I, Section 2, Chapter 55, pgs 667-674.
2. Dogru M, Asano-Kato N, Tanaka M, et al. Ocular surface and MUC5AC alterations in atopic patients with corneal shield ulcers, Curr Eye Res., 2005 Oct;30 (10): 897-908.
3. Bacon, AS., Tuft, SJ, Metz, DM., et al. The origin of keratopathy in chronic allergic eye disease: a histopathological study. Eye 1993 7(3): 21-25.
4. Donaldson KE, Karp CL, Dunbar MT. Evaluation and treatment of children with ocular rosacea. Cornea. 2007 Jan;26(1):42-6.
5. Cetinkaya A, Akova YA. Pediatric ocular acne rosacea: long-term treatment with systemic antibiotics. Am J Ophthalmol. 2006 Nov;142(5):816-21.

Dr. Dunbar is the director of optometric services and optometry residency supervisor at the University of Miami's Bascom Palmer Eye Institute. You can e-mail him at mdunbar@med.miami.edu.