The differential diagnoses would include inflammatory and infectious causes of pediatric ocular surface disease. Infectious etiologies could include herpes simplex, although it most commonly presents unilaterally there are more severe cases with bilateral disease [1]. Allergic or immune causes include vernal keratoconjunctivitis, although vernal is more common in boys and is typically associated with giant papillae and shield ulcers [2]. From the description we know that the process is bilateral with involvement of the eyelids, conjunctivae, and corneas. The most likely diagnosis is phlyctenular keratoconjunctivitis in the setting of chronic blepharitis, which is very prevalent in children [3, 4].

There are a few more relevant historical questions to ask. You would want to know if this child has a history of oral cold sores and whether she has a history of rosacea. You would also ask if any history of contact lens wear. A history of recurrent chalazia is also consistent with the diagnosis of phlyctenulosis and frequently present.

The most important element to recognize is the significant inflammation. The severe vision impairment in the left eye along with the dramatic corneal appearance of stromal haze, lipid deposition, and angry neovascularization does make one concerned for possible destructive infectious processes, but antibiotics or antivirals alone will not treat this vision-threatening condition. Anti-inflammatory activity is necessary to dampen the immune reaction that is causing lipid deposition, loss of corneal clarity, and neovascularization. The best initial approach includes topical steroids and oral anti-inflammatory and antibiotic therapy appropriate for this age group in addition to eyelid hygiene (preferably with eyelid cleansers) with warm compresses.

Oral erythromycin can be an effective systemic agent for ocular surface inflammation in the pediatric age group. The macrolides’ bacteriostatic properties have been found to inhibit production of pro-inflammatory cytokines and thus have been useful as an anti-inflammatory agent for the eye [5]. The challenges in compliance are tied to its requirement of multiple daily dosing.

Doxycycline , which is an inexpensive, effective option in adults and older children for ocular inflammation, has been generally contraindicated in children less than 9 years of age due to concerns of deposition of the drug in bone and teeth. However, it has been used safely in many children with manifestations of ocular rosacea with good control of their disease [6]. Due to the petite frame of this child and the other alternatives, we decided to defer the option of doxycycline for management of her disease until she is older.

Topical antibiotics are not necessary in this child because clinically her exam is consistent with inflammatory processes and there is no ulceration or epithelial breakdown to suggest ocular surface compromise with microbes. As discussed below, there may be a role for topical antibiotics to the lid (to reduce the microbial flora); however we prefer to start with systemic medications.

The goals of therapy include suppression of the ocular surface inflammation and resultant vision-threatening scars. However, one must recognize the significant side effects of the medications involved and carefully titrate to effect while also minimizing potential adverse effects. Topical steroid therapy is well known to elevate intraocular pressures, and children are more vulnerable to this problem than adults [7]. In addition, lenticular changes that can cause vision loss are also a potential concern. However, one must realize that when balancing the competing factors involved in visual preservation, corneal destruction and scarring can often be much more difficult to ultimately treat compared with the resources we have to mitigate intraocular pressure rises and cataracts. Corneal transplantation in children is fraught with challenges [8], especially in the postoperative period, and in an eye prone to inflammation the risk of graft rejection is increased.

Cyclosporine has become widely used to mediate the inflammatory component of dry eye and has been shown to increase tear production [9]. It is commercially available in a 0.05% formulation but can be compounded in a 2% formulation for more severe ocular surface disease. In a series of children with a mean age of 9 years old, the cyclosporine 2% was given four times a day for an average of 1 year with significant resolution of ocular surface inflammation. These children were selected due to poor response to topical steroids and oral antibiotics, and the topical cyclosporine was found to be well tolerated in this age group [10]. The steroid-sparing effect is clearly advantageous. Although it is not FDA approved for the treatment of phlyctenular disease in children, the literature confirms its utility for this indication as an off-label ophthalmic use.

She was not tolerating the oral erythromycin, so we switched her to oral azithromycin in addition to continuing the topical anti-inflammatory therapy. She was able to get the cyclosporine 0.05% covered. Her vision within 2 months of treatment was improved to 20/50 in the left eye (Fig. 16.1c , d ).

As discussed earlier, doxycycline and erythromycin have been used in children when age and dose appropriate for the control of ocular surface inflammation. If these agents are poorly tolerated or contraindicated, another option that has recently been highlighted for the pediatric population is azithromycin. Oral azithromycin, dosed 5 mg/kg/day with a single daily dose, has been shown to have effective anti-inflammatory effect on the ocular surface in children with phlyctenular disease [11]. It is commonly given at that dose for approximately 1 month and then given at half dose for another month. It is well tolerated, and the once a day dosing in our experience has been great for compliance in the pediatric population.

Azithromycin has also been utilized in its topical form to treat children with this disease. One formulation studied was azithromycin topical ophthalmic solution 1.5%, and in a series of 16 children ranging in age from 4 to 16 years old who had disease poorly responsive to other typical therapies, the majority of children were found to have tolerated the eye drops (two stopped therapy due to ocular irritation), and only one child required additional therapy for disease control [12].

Any ocular surface disease has the potential to cause scarring or vision-threatening opacities. In the amblyopic age group, it is critical to remember that early intervention is the key to preservation of vision. Therefore, when a child presents with corneal scarring or severe keratitis that is primarily unilateral or asymmetric, they should be assessed for the risk of development or presence of amblyopia. Sometimes this requires early patching or more aggressive therapy than one might institute in an adult with the same findings, so as to prevent deprivational amblyopia.

She continues to have recurrent episodes of ocular inflammation ( Fig. 16.2 ) in the left eye with deeper corneal neovascularization, despite topical and oral steroids, topical cyclosporine, and oral azithromycin .

Recalcitrant phlyctenular disease can be approached using localized therapy to the eyelids, which are often the source of the inflammation. Topical tacrolimus applied to the eyelids has been proven efficacious in reduction of ocular inflammation in these more challenging cases. Tacrolimus has been shown to have a potency 30 times more than cyclosporine. The formulation evaluated in the pediatric age group for this indication is 0.03% tacrolimus ointment to the lower fornices twice daily for a few weeks with good results and was well tolerated [13].

Our patient did not initially tolerate the tacrolimus preparation available, but we recommended dilution of the ointment with artificial tear lubricating gel, and she was able to tolerate it and achieve good effect. With institution of the above alternative therapy, the robust inflammation in her left eye became quiescent, and her vision measured 20/30 ( Fig. 16.3 ).

Phlyctenular keratoconjunctivitis is a common inflammatory ocular surface condition in children with many available therapies. In many literature series, the larger spectrum of blepharokeratoconjunctivitis, of which phlyctenular disease is a subset, represents the most common referral diagnosis for pediatric patients to ophthalmic referral centers. Phlyctenular disease has traditionally been associated with a hypersensitivity reaction of the ocular surface, namely, the cornea and the conjunctiva, to bacterial antigens. The most common agents implicated are tuberculosis, Staphylococcus, and chlamydial antigens, although other less common antigens can also trigger this disease process [14]. In patients with recalcitrant disease, it may be reasonable to check for tuberculosis (Quantiferon Gold). Phlyctenular disease can also occur in the setting of chronic eyelid inflammation, and therefore a multipronged approach to the ocular surface destruction, eyelid inflammation, and bacterial hypersensitivity is critical. Another condition that must be considered in recalcitrant disease is demodex. Diagnosis requires examining lashes under light microscope. Current treatments for demodex include eyelid scrubs with 50% tea tree oil or oral or topical ivermectin [15].

Vision-threatening and amblyogenic scarring can occur, especially since the average age of presentation of these children is reported to be around 6 years old [14–17]. Therefore, we must consider visual development in the context of therapeutic decisions and potentially involve pediatric ophthalmologists in the disease management process if the child is perhaps being managed by an internist or ophthalmic subspecialist who may not treat amblyopia as part of their daily practice.

AA is a 5-day-old infant female transferred to the neonatal ICU from an outside hospital for escalation of clinical care. You are consulted for further ophthalmic evaluation and management by the ICU team. Prenatal history is significant for poor prenatal care and alcohol abuse during pregnancy. She was born at 37 weeks without complications, but birth weight was noted to be in the third percentile ( Fig. 16.4a , b ).

On general examination, the patient has multiple, severe malformed features. Facial abnormalities include a sloped forehead, hypertelorism, flattened nasal bridge, macrostomia, micrognathia, deformed ear lobes, thin upper lip with long philtrum, and reduced hair of the scalp and eyebrows (Fig. 16.4a ). She also has absent nipples, abnormal skin tension throughout her entire body with absence of hair or lanugo, and abnormal genitalia.

On ophthalmic examination, she is found to be averse to light in either eye. There is full extraocular motility, and intraocular pressures measured by portable Tonopen are 10 mmHg in both eyes. On external exam, there is an absence of eyelids, eyelashes, and eyebrows with scant orbicularis muscle present with retraction of the globe when blinking (Fig. 16.4b ). There is marked conjunctival injection and chemosis bilaterally. The corneas are found to be opacified with infiltration and 60% thinning bilaterally and with associated corneal epithelial defects of 5 and 6 mm in the right and left eyes, respectively. Corneal diameters are 7 mm OD and 8 mm OS. There is no view to the anterior chamber, iris, or lens. B-scan ultrasonography does not reveal any posterior abnormalities.