Case Report: Managing a case of Tubercular Phlycten presenting as Sterile Corneal Perforation

Introduction

Phlyctenular keratoconjunctivitis (PKC) is a cell-mediated allergic reaction of the conjunctiva or cornea. It might be caused by several antigens, including tubercular proteins and staphylococcal by-products.^1–3 Corneal phlyctens usually presents with a limbal nodule that ulcerates at the apex within 1-2 weeks. Phlyctens are acute but usually self-limiting and corneal phlyctens rarely perforate.⁴ In the literature, only a few cases of perforation have been reported after non-tubercular PKC.^5–7 In this paper, we present a unique case of tubercular PKC, presenting with corneal perforation and a brief review of the literature.

Case report

A 22-year-old Indian male farmer presented with complaints of a whitish mass that grew gradually and painlessly in the left eye. He consulted locally, where he was diagnosed with a limbal nodule. There was no relevant family history. Previous medical report have described the limbal nodule to be 2×2 mm with a leash of blood vessels migrating towards the cornea from 5 to 6 o’clock position. He was started on topical prednisolone acetate 1% (4 times/day) and moxifloxacin 0.3% (8 times/day). After one month, he developed diminution of vision and presented to our clinic. He was worried as his vision has decreased suddenly.

There was no history of ocular trauma. The right eye was functioning within normal limits. His uncorrected visual acuity (UCVA) was 20/20 and 20/80 in the right and left eyes, respectively. In the left eye, the conjunctiva was congested, and a 3×3 mm corneal perforation was observed at the 5 o’clock position, with iris tissue plugging the perforated site (Figure 1a). Both lids were healthy, with no signs of blepharitis. The fundus examination was also within normal limits.

Figure 1. (a): A 3×3 mm corneal perforation on presentation. (b): Postoperative day one picture showing corneal patch graft. (c): Persistence of surrounding stromal edema due to DMD (marked with an arrow in AS-OCT). (d): Picture showing the well-integrated patch graft (marked with an arrow in AS-OCT) on the last follow-up visit.

There was no infiltration or stromal cellularity around the perforated area, ruling out an infectious etiology. Peripheral ulcerative keratitis (PUK) with or without any autoimmune etiology was considered. However, the absence of an overhanging epithelium or stromal thinning in the adjacent area ruled out PUK. Considering the age, ethnic preponderance, and clinical picture, a provisional diagnosis of phlyctenular keratitis with perforation was suspected. The patient had no history of chronic cough, fever, weight loss, or night chills. He was advised investigations such as a total leukocyte count (TLC), erythrocyte sedimentation rate (ESR), and Mantoux intradermal tuberculin skin test (TST). In the meantime, he underwent a corneal patch graft to restore the anatomical integrity of the globe. The prolapsed iris tissue was abscised intraoperatively, and an unused anterior stromal cap (from the previous Descemet’s stripping keratoplasty procedure) was trephined and utilized. The 3.5 mm lamellar, circular, corneal cap was secured with six interrupted 10-0 nylon sutures. Postoperatively, the graft was in place, though mildly edematous, and the anterior chamber was well formed (Figure 1b). He was started on topical antibiotics (ofloxacin 0.3%, 4 times/day) and steroids (prednisolone acetate 1%, 8 times/day).

In the meantime, the patient’s blood investigation showed elevated TLC (11.7×10⁹/L) and ESR (69/mm³ in the 1^st h). TST was strongly positive, with 75 mm of induration read at 48 hours. The patient was also prescribed an interferon gamma release assay (IGRA, QuantiFERON Gold) for further confirmation. The IGRA was positive, and he was referred to a physician. The chest radiograph showed no active lesions, and a diagnosis of latent tubercular infection (LTBI) was established. The patient was started on a multi-drug anti-tubercular therapy (ATT) of oral Isoniazid (750 mg) and oral rifapentine (750 mg), once weekly for three months, and oral rifampicin (600 mg), once daily for four months for the LTBI.

At the 1-week postoperative visit, the stromal edema persisted (Figure 1c), and Descemet’s membrane detachment (DMD) was observed in a small area adjacent to the graft, which was managed using air descemetopexy. The DMD could have resulted from the reforming of the anterior chamber postoperatively. Topical steroids (prednisolone acetate 1%, in weekly tapering doses), topical antibiotics (ofloxacin 0.3%, 4 times/day), and oral ATT were continued. Subsequently, the stromal edema subsided, and all the sutures were removed after six weeks. The graft-host junction was well apposed (Figure 1d), and the patient regained a UCVA of 20/25, improving to 20/20 with glasses at the final visit. The perforated site healed with scar formation, and the integrity of the globe was maintained. Since the perforation was at the perilimbal site, the patient’s visual acuity was not affected much.

Discussion

PKC is a cell-mediated allergic reaction to antigens, such as-tubercular proteins, staphylococcal by-products, parasites, or other microbes.^1–3 It is usually seen in the low socio-economic strata during the first two decades of life, with a few reports suggesting female pre-ponderance (though some reports depict no gender predilection).^8–10 Reports from some Asian countries show that TB accounts for approximately 77% of cases of PKC. PKC is usually seen in pulmonary and lymph node TB; however, LTBI has also been implicated as an etiology.¹¹ The patient in our case report was also a young Indian male from a low socio-economic background. He had no suggestive symptoms or contact with an active case of TB infection. TB is an endemic disease in the Indian subcontinent; therefore, investigations were done to rule out a tubercular infection.

The clinical presentation depends on the location of the lesion and the underlying etiology. Corneal or TB-related phlyctenules are usually more symptomatic than conjunctival or staphylococcal-related phlyctenules.⁴ The most common site for phlyctenules is inferiorly (4-8 o’clock area). The infection presents either as a conjunctival or corneal gelatinous nodular lesion. As the lesion progresses, it ulcerates and shows positive fluorescein staining at the apex.^4,12 Conjunctival phlyctens are transient nodules that rarely cause permanent scarring. In contrast, corneal phlyctenules migrate from the limbus to the cornea, leaving a leash of pannus behind.¹³ In our case report, the documentation of the presence of a limbal nodule with a leash of blood vessels prior to presentation led to the suspicion of PKC. Moreover, most of the cornea was clear at presentation, ruling out an infectious cause or PUK as an etiology. No blepharitis or acne rosacea was observed in our case.

In TST, a standard dose of 5 tuberculin units (0.1 mL) of purified protein derivative is injected intradermally and the results are read between 48-72 h.¹⁴ Though it is a cheap and easy-to-perform test, the Bacille Calmette Guerin (BCG) vaccine is associated with a high risk of false positive results.¹⁵ Therefore, in countries (like India) where BCG is a part of childhood immunization, skin induration of >15 mm is more suggestive of tuberculosis infection.¹⁶ Moreover, IGRA increases the positive predictive value, as the BCG vaccine does not interfere with the test.^17,18 In our case, both TST and IGRA were strongly positive but symptoms of active TB or findings on the chest radiograph were negative. Therefore, he was started on an ATT regimen for LTBI, as per guidelines of the World Health Organization.¹⁴

Corneal perforation is rarely reported in corneal phlyctens, as most cases heal by scar formation. Topical steroids are the first-line treatment for PKC,³ with severe cases warranting topical immunomodulators.¹⁹ Our patient presented with a 3×3 mm perforation, and simply applying cyanoacrylate glue would not have sufficed. Therefore, a corneal patch graft was required.²⁰ The advantage of corneal patch graft is rapid closure of perforation, but one needs tissue to be readily available. Apart from support from the eyebank, there could be chances of suture-related complication, such as hyphema, DMD (as seen in our case) and infections in worst case scenarios.²¹ In literature, similar cases had been reported in non-tubercular PKC. The perforations had been treated with either cyanoacrylate glue, corneal patch graft, or left to heal with systemic tetracyclines or soft contact lenses based on the size of the perforation.^5–7 The location of the lesions is also important. Peripheral lesions close to the limbus usually heal well with scar formation. Even if a patch graft is performed, the visual acuity is mostly unaffected. Cases involving the visual axis are difficult to treat and may require an optimum-sized optical keratoplasty. In a previous case report, the corneal patch graft led to opacification in the visual axis, requiring penetrating keratoplasty later.⁷ Table 1 shows the published case reports of perforations in PKC. Among the five reported cases of PKCs with perforations, none had TB as the etiology.^5–7

To the best of our knowledge, this is a unique case of tubercular PKC, presenting as a perforation. As perforations are rare in PKC, such cases can be overlooked, and other differentials, such as sterile melts in PUK, trauma, or infective perforations, may be considered. However, careful examination of the surrounding epithelium, stroma, and lids will help in reaching the correct diagnosis. In endemic countries, once the diagnosis of PKC is considered, the subject should be tested for TB. The risk of LTBI is approximately 33%. Therefore, these cases should be investigated for any active disease. Even if no active disease is present, timely ATT reduces the risk of reactivation.²² Timely ATT is also important as the close differential is PUK. Supposedly systemic immunosuppression were started in this case (as the perforations are common in PUK than PKC and also ESR was raised), it would have wreaked havoc leading to reactivation of the latent TB infection.

Therefore, in young patients from low socio-economic strata presenting with inferior conjunctival or corneal lesions, a diagnosis of PKC should always be kept in mind. In such patients, a thorough examination of the lids and laboratory analyses helps to establish the etiology. Once TB is established as an etiology, a multidisciplinary approach should be planned. An immediate referral to the nearest pulmonologist/physician can prevent systemic complications. Hence, appropriate evaluation and timely ocular and systemic intervention remains the key to successful management. This case report also emphasizes the role of an ophthalmologist in finding a serious systemic infection lurking underneath the mask of ocular pathologies.

Consent

Written informed consent for the publication of the case report and any associated images was obtained from the patient prior to submission.

Author contributions

AJK contributed to the study conceptualization, study investigation, methodology, manuscript editing, and revision. SD and SMR contributed to the original draft preparation, study methodology, and revisions.

Author roles

Kaur A: Data Curation, Methodology, Visualization, Writing – Original Draft Preparation.

Das S and Priyadarshini SR: Conceptualization, Data Curation, Funding Acquisition, Investigation, Methodology, Project Administration, Supervision, Validation, Visualization, Writing –Review & Editing.