A 52-year-old Caucasian female with a history of ocular surface dysfunction presented with severe pain and decreased vision in her left eye. The patient’s medical history included an instance of severe corneal involvement while vacationing overseas that resulted in hospitalization and successful treatment with autologous serum. She also had a history of autoimmune disease relating to systemic lupus but no ocular trauma, and reported undergoing an evaluation for medical concerns in the past, none of which were positive.  

Initial examination demonstrated a relatively normal right eye with acuity of 20/25+ sans correction. The left eye displayed an area of epithelial loss inferiorly measuring 6mm horizontally by 1.5mm to 2mm vertically. Additionally, the anterior chamber demonstrated trace cellular reaction. No evidence of infiltrative keratopathy or neutrophil activity was present in either the abnormal zone or the area surrounding it. Tear osmolarity measured 316 in the right eye and 298 in the left.

The corneal area with epithelial damage stained actively with Fluress; however, no significant adjacent tissue involvement with the dye was identified. Lissamine stain showed notable bilateral conjunctival involvement, and the left eye also demonstrated a mild superior limbic keratoconjunctivitis. Applanation pressure in the right eye measured 16mm Hg and was deferred in the left side due to the corneal issue. The patient was dilated at the evaluation and demonstrated normal posterior poles in both eyes at 0.3 cup-to-disc ratios, flat optic nerves and non-remarkable posterior poles and peripheral retinas.

The patient reported she had awakened with the painful issue, which had been preceded by several days of a notable foreign body sensation in the left eye. Potential causes for the presentation included her history of severe dry eye for which she had been treated chronically over the years, recurrent corneal erosion, corneal dystrophy, trauma or toxicity; however, currently, she was not using any topical lubrication or active therapeutic agents. A bandage contact lens and a therapeutic regimen consisting of one drop of Ciloxan (ciprofloxacin 0.3%, Alcon) QID was initiated, and homatropine 5% was also administered twice in the chair. The patient was advised to use non-preserved artificial tears QID in alternation with the antibiotic. 

The Twist
The patient returned to the office on day three with a visual acuity of light perception. The involved eye was 4+ injected with intense ciliary flush and the epithelial lesion was unchanged from the previous examination. Additionally, the patient’s contact lens was no longer present and she reported avoiding use of the topical antibiotic, as her dog had “chewed the bottle” the day after it was prescribed.

Slit lamp examination revealed a 6mm by 2mm corneal wound consistent with the initial evaluation. The patient also demonstrated an anterior chamber hypopyon, which was accompanied by a 4+ cellular reaction and early fibrinoid activity. Dilation was performed with tropicamide, phenylephrine and homatropine 5% to maximize pupillary activity, and homatropine 5% was administered again 45 minutes later to relieve the patient’s discomfort.  

The dilated fundus exam did not show a view of the posterior pole, in part due to the hypopyon and anterior chamber reaction and secondary to a dense vitreous response. The cornea demonstrated multiple infiltrates approximately 1mm in size in an arc above the primary lesion, extending from 4 o’clock to approximately 10 o’clock. None of the infiltrates stained actively. B-scan ultrasonography demonstrated a 3+ cellular reaction in the posterior vitreous. A sonolucent zone was also present posterior to the hyaloid face with a crescent-like area of clarity.  

The patient was advised that the decline of her condition was significant and that her noncompliance with the treatment could be contributory. The keratouveitic response was a particularly notable point of concern and the possibility that an endophthalmitis was present should not be ruled out. In a somewhat comforting finding, the area posterior to the hyaloid face was sonolucent; a typical endophthalmitis would not respect an anatomic boundary that acutely. At this point, the patient was placed on Zymaxid (gatifloxacin, Allergan) q1hr and atropinized in the chair.

A consultation for the notable vitritis present yielded the conclusion that the presentation was not endophthalmitis. Instead, the problem was identified as a remarkable keratouveitic response to the primary lesion and subsequent corneal involvement. At this point, a Prokera amniotic membrane was placed on the eye and alternate dosing therapy with Zymaxid and vancomycin was initiated to provide full antibiotic coverage. The patient was also placed on a regimen of 500mg of oral Valtrex (valacyclovir, GlaxoSmithKline) PO TID, since the lesion was nonresponsive in the first four days and the etiology was unclear as to onset. The patient was also advised to use atropine QD to quiet the ciliary body. 

The patient continued to be monitored daily for the next three days, during which the hypopyon began to resolve and comfort improved by approximately 50%. The lesion itself was difficult to evaluate, so the membrane was removed under sterile conditions and stored in a sterile solution while the cornea was assessed. Observation demonstrated a 60% to 70% improvement in the size of the lesion and epithelial cellular development in the margins. A notable reduction in the hypopyon, as well as the overall level of inflammatory cellular activity, was also noted in the anterior chamber.

The Prokera was replaced using a sterile technique and the patient continued with current therapy. She returned to the clinic two days later exhibiting a completely sealed corneal defect with intensive staining at the margins, but good healing response. At this point, the hypopyon had cleared by over 90% and the anterior chamber had significantly improved. A B-scan assessment also revealed marginal improvement in the posterior segment and vitreous fluid. Visual acuity at this visit was 20/300, which did not improve on pinhole. This was consistent with the last several visits, including the assessment of visual function at the time when the Prokera was removed for review of the cornea.  

Given this good response, the decision was made to begin tapering the topical antibiotic therapy. The oral Valtrex regimen was maintained, however, as there was notable improvement in the patient’s condition following initiation. One drop of Durezol (difluprednate, Alcon) QID was also added. The patient was directed to return on a two-day cycle for the next 10 days. During this period, the cornea continued to improve, with a further decrease in staining; the infiltrates remained stable and nonprogressive; the hypopyon dissipated; and the anterior chamber reaction reduced to trace findings. Intraocular pressure measured on several occasions was within the normal range. Visual acuity improved to approximately 20/200, and pinholed to 20/150; there was also a substantial decrease in the number of vitreous cells present.

By the tenth day following intensive therapy, the antibiotics were being taken QID, the Valtrex had been reduced to QD and the Prokera membrane had been removed. The patient was also directed to use Refresh PM (Allergan) TID following application of the antibiotic and steroid drops. The patient was subsequently scheduled to return on a weekly basis. During her most recent examination, visual acuity was 20/40 in the treated eye, which pinholed to 20/25-. The epithelial lesion was completely closed and the re-epithelialization process had produced a relatively smooth epithelial surface. Stromal infiltrates were still present, but inactive. Additionally, the anterior chamber was quiet and there was a significant reduction in vitreous cells. At this point, all topical antibiotic therapy was discontinued and the patient was directed to continue taking oral antiviral therapy QD and Refresh PM TID, interspersed with nonpreserved artificial tears. She also continued using one drop of Durezol daily, with the expectation that the posterior cellular activity would clear more rapidly as a result.

This case shows a remarkable response with relatively ordinary initial factors, in that the patient’s history of dry eye and compromised autoimmune status likely produced a recurrent erosive episode and possible atypical HSK presentation. Subsequently, either of these—or both—ignited a 4+ keratouveitic cascade that progressed to a hypopyon and vitritis, ultimately requiring a month-long healing process back to improved visual function. 

Overall, it is important to remember that autoimmune deficiencies can induce a wide variety of unexpected responses, including the type seen in this patient. Other patients to keep an eye on for this type of response include those undergoing cataract or refractive surgery.