Introduction

Topical nonsteroidal anti-inflammatory drugs (NSAIDs) have been widely employed in cataract surgery for many years and have been proven to be safe and effective [1]. Nonetheless, their use has been associated with several mild topical adverse events, the most common of which are ocular stinging, or a burning sensation after instillation, mild conjunctival hyperemia, local infection, and reduction of corneal sensation [1]. With regard to corneal complications, topical NSAIDs have been reported to cause superficial punctate keratitis, sterile corneal infiltrates, and persistent epithelial defects. However, in general these complications require frequent dosing and prolonged use [1]. Among rare adverse events, corneal melting is the most severe and potentially sight-threatening [2]. It is thought that corneal melting occurs due to collagen degradation triggered by defects of the corneal epithelium [2].

It should be noted that worldwide, except for topical NSAIDs, several topical formulations with antiseptic, lubricating, and moisturizing properties are also used preoperatively in cataract surgery to improve the health of the ocular surface and potentially to diminish the risk of postoperative infection [3]. It is well documented, however, that when preserved topical medications are employed the preservatives they contain (mainly benzalkonium chloride) exert a toxic effect upon the corneal epithelium [3].

We present a case of acute corneal melting in an elderly patient most likely induced by the brief, concomitant use of a topical NSAID (bromfenac) and antiseptic eyedrops, which were only briefly instilled in preparation for scheduled cataract surgery. Our patient did not provide any known history of ocular or corneal disease did not use any medication, did not manifest ocular surface disease, nor exhibit signs of a previous corneal epithelial defect, at the preoperative examination 4 days before the occurrence of corneal melting. To the best of our knowledge, topical NSAIDs have never been described as causing acute corneal melting when used briefly combined with antiseptic eyedrops prior to cataract surgery.

Case Report

A 70-year-old healthy female patient was urgently referred to our department due to acute corneal perforation in her left eye (OS). At the time of admission, she reported moderate ocular discomfort, tearing, and foreign body sensation. The patient did not give any known history of previous ocular or systemic disease and stated that until recently she had not used any topical or systemic therapy. She noticed a gradual reduction in her visual acuity affecting both eyes (OU) over a period of 1 year and she visited her local ophthalmologist who diagnosed bilateral senile cataract and scheduled her for cataract surgery OS. Her ophthalmologist prescribed bromfenac eye drops (Yellox® 0.9 mg/ml, Bauch&Lomb) twice daily and Desodrop® eye drops (Bauch&Lomb) four times daily in her left eye for 4 days prior to the day of phacoemulsification surgery. She had only used this preoperative regiment for 2 days prior to the development of acute visual loss OS, and was referred to us as an emergency case of corneal perforation OS. When seen, her uncorrected distant visual acuity in the affected eye was only hand motion. Slit-lamp examination revealed a very shallow anterior chamber, diffuse inferior corneal melting with an area of full-thickness perforation measured 1 × 2 mm, and a positive Seidel test (Fig. 1A). No sign of infection was observed. The patient was hospitalized and the eye drops she was using were discontinued. The corneal perforation was managed by the application of cyanoacrylate glue and a bandage contact lens was used in combination with moxifloxacin eye drops (Vigamox® 5 mg/ml, Alcon Inc) applied hourly. Two hours later, the anterior chamber started to reform; the following day, the anterior chamber depth was fully restored (Fig. 1B). Two weeks later, the bandage contact lens was removed, the glue was detached, and full epithelial re-growth was seen. The anterior chamber was deep without signs of inflammation (Fig. 1C). Her unaided vision improved to 20/80, while her best-corrected distant visual acuity was 20/40 (− 2.00, − 4.00 × 90), with an area of inferior corneal thinning. This case report followed the tenets of the Declaration of Helsinki. Informed consent was obtained from our patient.

Fig. 1
figure 1

Inferior corneal melting with an area (1 × 2 mm) of full-thickness perforation and shallow anterior chamber. No corneal neovascularization or infiltration observed (A). B Closure of the corneal perforation, and anterior chamber restoration after the application of cyanoacrylate glue. C Detachment of cyanoacrylate glue, following the full epithelial regrowth of the cornea

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Discussion

Worldwide, topical NSAIDs are commonly employed in preparation for cataract surgery to reduce perioperative ocular discomfort and inflammation. More importantly, by improving mydriasis, NSAIDs may also reduce the rate of surgical complications [1]. However, the remote possibility exists that in susceptible individuals, chronic NSAID therapy may induce unwanted, sight-threatening adverse events like corneal melting [2]. It is important to highlight that the use of ocular NSAIDs requires additional triggering factors to induce corneal melting. Certain ocular conditions, including severe dry eye disease, keratoconus, recent ocular surgery, and systemic immune-related diseases, such as rheumatoid arthritis, Sjögren’s syndrome, rosacea, and diabetes mellitus, predispose to the development of moderate-to-severe ocular surface disease with resultant epithelial defects.

The pathogenesis of corneal melting appears to begin with the development of a corneal epithelial defect, which, when not healed, can lead to a breakdown of the stroma through the hydrolysis of collagen fibers, resulting in corneal thinning, descemetocele formation and, in severe cases, corneal perforation. Eicosanoids and matrix metalloproteinases (MMPs) are the main signaling molecules in this process, while prostaglandin E2 (PGE2) is thought to be a protective influence for corneal integrity. Conceivably, by preventing the synthesis of this, or other similar protective molecules, NSAIDs facilitate corneal melting [2].

Bromfenac sodium, also known as 2-amino-3-(4-bromobenzoyl) benzeneacetic acid sodium salt, is a NSAID that has been approved in Europe for topical ocular use. It is widely recognized as a standard treatment option for ocular surface inflammation and various ocular conditions, including allergic conjunctivitis and postoperative inflammation. There have been several reported cases of corneal melting resulting from the chronic use of bromfenac eye drops in patients with pre-existing ocular surface disease [4].

The antiseptic Desodrop® solution contains polyhexamethylene biguanide (PHMB), which is recognized for its broad-spectrum antimicrobial and antifungal properties. Indeed, this agent is widely used as a standard treatment for acanthamoeba keratitis and is employed in multipurpose antiseptic eye drop regiments before cataract surgery. It should be noted, however, that a study that compared the effects of preoperative antiseptics before cataract surgery reported superficial punctate epitheliopathy to be a relatively common finding in the PHMB group [5]. Further evidence concerning the safety of intrastromal injection of PHMB suggested that it may have a harmful impact on ocular surface epithelia, particularly when administered at a concentration of 0.02% or more [6]. The need for using antiseptic eyedrops as a preoperative measure before cataract surgery remains uncertain. Further research is essential to comprehensively explore the composition and dynamics of the eye microbiota [7] and to assess the effectiveness of antiseptic eyedrops in preventing postoperative infections. It is crucial to determine whether such interventions are truly necessary while preserving the natural ocular microbiome, balancing potential benefits with potential risks or drawbacks.

Considering that the patient had no known prior ocular history, we assume that the combined use of these eyedrops resulted in the acute corneal melting. However, we cannot rule out the possibility of a pre-existing epithelial alteration due to ocular surface disease or a potential corneal abrasion caused while instilling the medications. It is plausible that the presence of a preexisting corneal defect or surface disease could have facilitated the acute corneal perforation, exacerbated by the interaction between NSAIDs and antiseptic drops, ultimately leading to corneal melting. In summary, our case suggests that the concurrent use of PHMB antiseptic and bromfenac eyedrops, even for a short duration, can rarely trigger corneal epithelial damage, especially if the epithelium has minor pre-existing damage or an asymptomatic ocular surface disease, which may culminate in acute corneal melting and perforation. Therefore, caution is advised when using NSAIDs and antiseptics in elderly individuals. These preoperative regimens may, in many cases, be unnecessary and their combined use can be avoided when preparing low-risk elderly individuals for cataract surgery. If such a regimen is chosen, additional monitoring may be necessary.