Secondary Corneal Myxoma After DMEK (Descemet Membrane Endothelial Keratoplasty)

Background

Myxomas are rare benign tumors that appear in mesenchymal tissue, mainly in peripheral muscles and the heart, particularly the left atrium [1,2]. Myxomas can also develop in periarticular areas and in the skin. They can be isolated or in association with Carney complex [3–6]. In ophthalmology, myxomas can be found under the eyelid [7], in the conjunctiva, and in the cornea, and only 20 cases of corneal myxoma have been reported [8–13].

In the cornea, myxomas are divided into categories of primary tumoral lesions and secondary lesions, following a pre-existent corneal or conjunctival lesion, also known as secondary myxomas, or myxomatous corneal degeneration.

Here, we report a case of secondary corneal myxoma, which developed following a viral endotheliitis, treated with a Descemet membrane endothelial keratoplasty (DMEK) lamellar graft.

Case Report

A 52-year-old male, with no prior clinical history, presented in March 2016, with an endotheliitis in the left eye. The endotheliitis seemed to have evolved over several months, and the patient mainly complained of visual acuity loss.

The initial slit-lamp examination showed an important conjunctival hyperemia, an altered ocular surface with superficial keratitis and corneal hypesthesia, an inflammatory reaction in the anterior chamber with a grade 3+ Tyndall effect according to the SUN (Standardization of Uveitis Nomenclature), and an endothelial decompensation, with corneal edema and Descemet folds.

Paraclinical explorations did not allow the etiology to be determined. The genome of herpes simplex virus was searched by polymerase chain reaction (PCR) after a puncture of the anterior chamber, which yielded negative results. The hypothesis of an undetected herpes infection was favored, and an anti-viral treatment was prescribed, using valacyclovir (1 g orally, 3 times daily).

After 3 months of antiviral treatment, the endotheliitis was successfully controlled and a combined intervention of DMEK endothelial graft and phacoemulsification was performed. The best corrected visual acuity (BCVA) of the left eye prior to the intervention was 1.3 logmar.

The inflammatory reaction in the anterior chamber was controlled, but there was still a pathologic ocular surface with conjunctival hyperemia, despite treatment with lubricants.

Postoperative treatment consisted of Cosopt® (eye drop, dorzolamide 2%+timolol 0.5%; Santen France), Tobradex® (eye drop, tobramycin and dexamethasone, Alcon, Novartis Pharmaceuticals, France), and antiviral treatment, valacyclovir (1 g orally, 3 times daily).

A rapid improvement of BCVA was observed 15 days after the intervention (0.05 logmar), and after 6 weeks (0 logmar). Tonus was normalized after reinforced hypotonic treatment with Ganfort® (eye drop, bimatoprost 0.3 mg/mL+timolol 5 mg/mL; Allergan France) and Simbrinza® (eye drop, brinzolamide 10 mg/mL+brimonidine 2 mg/mL; Alcon, Novartis Pharmaceuticals, France). Nevertheless, the patient’s left eye still presented an altered ocular surface.

Satisfactory postoperative results allowed for a diminution of the corticosteroid therapy after 3 months, which then was replaced by Flucon® (eye drop, Fluorométholone Alcon, Novartis Pharmaceuticals, France). Antiviral treatment was also lowered to a residual dose, valacyclovir (500 mg orally, once daily).

Fifteen months after the intervention, the patient complained of a decline in visual acuity in the left eye. His BCVA was then 0.3 logmar for the left eye, with persistent conjunctival hyperemia. This eye presented with corneal edema as well as supranasal neovascularization and stromal haze, but there was no visible inflammation in the anterior chamber.

An injection of betamethasone was performed under the conjunctiva, associated with local corticosteroid therapy, with no clinical improvement. A new puncture of the anterior chamber was undertaken in order to search for the herpes simplex virus in the aqueous humour, with negative results. A complete check-up revealed the development of Crohn’s disease, which was treated with azathioprine, orally (2 mg/kg short term, 50 mg daily long term).

Three months later, the ocular lesion became white and opaque, with round and well-defined edges (Figures 1, 2). It measured 9×5 mm and covered almost the entire upper half of the cornea.

Some vascularization was visible in the interior of the lesion. An anterior segment optical coherence tomography (AS-OCT) (OCT NIDEK RS 3000, NIDEK SA, 94042 Créteil, France) was performed, revealing a round and homogenous form that developed in the corneal epithelium and Bowman’s membrane, without affecting the stroma (Figure 3). Visual acuity was 1.3 logmar. A surgical dissection with a Crescent knife (Beaver™Xstar™Safety Crescent Knife, Becton Dickinson France S.A., F-38801 Le Pont-de-Claix Cedex) was performed, revealing a cleavage plane and a seemingly healthy cornea.

Histological analysis showed a myxoid lesion projecting from the stroma, between the epithelium and Bowman’s membrane (HES ×2.5; Figure 4A). The lesion was made of spindle or star-shaped fibroblastic elements, without cytonuclear atypia or mitosis (HES ×40; Figure 4B). The lesion was colored with Alcian blue (×2.5; Figure 4C). Immunohistochemistry analysis showed that tumoral cells were not targeted by anti-CD34 (×4; Figure 4D), anti-PS100, or anti-Actin smooth muscle antibodies. Proliferation index was estimated to under 1%, using Ki67 antibody.

The conclusion of the diagnostic was a secondary myxoma or a myxomatous corneal degeneration.

Postoperatively, the aspect became satisfactory one month after the intervention, both with biomicroscopy (Figure 5) and AS-OCT (Figure 6).

Discussion

Corneal myxomas are rare ophthalmologic lesions. Primary corneal myxomas are extremely rare and affect young people under the age of 15 years old, with no particular clinical background. On the other hand, most of corneal myxoid lesions occur in patients who have previously developed a corneal lesion such as traumatic or infectious corneal ulcers or keratoconus, or after a surgical treatment such as cataract surgery, keratoplasty, or photorefractive keratectomy [1–5,8–14] (See Table 1 [8–22]).

Secondary myxoma can affect patients of all ages, from 4 months to 80 years, with the average age of 52 years, and there seems to be a male predominance (15 males: 6 females). The delay between the presumed original lesion, or treatment, and the appearance of the myxoma can be very long, up to 10 years. Clinically, this lesion is characterized by a white, gelatinous tumor in the cornea. Differential diagnosis can be made with Salzmann nodular degeneration, keloid scar, pannus, amyloid deposition, or squamous cell carcinomas [10].

The evoked physiopathological hypothesis consists of a degenerative process, following the rupture of Bowman’s membrane, because of the transformation of corneal stromal keratocytes into myofibroblasts with significant secretory activity. Indeed, cells from the lesion usually express smooth muscle actin, suggesting cell differentiation towards myofibroblasts, as they cease to express CD34, a characteristic of normal keratocytes. Chronic corneal edema also seems to be a common physiopathological marker of these type of lesions [10].

The link between Crohn’s disease and the development of the corneal myxoid lesion is unknown, and to the best of our knowledge, such a link has never been reported. Crohn’s disease is known for provoking peripheral ulcerative keratitis (PUK), but the ocular surface of our patient did not show any ulcer that could evoke a PUK. This is also the first report of a secondary myxoma following a DMEK. Two stitches (nylon 10/0) secondary to the DMEK, present under the tumor, might have been the starting point for the irritation causing the tumor, but this hypothesis remains uncertain.

The treatment of secondary myxomas consists of a surgical excision of the lesion, normally without recurrence. Surgery can be limited to the tumor, or it can include a reconstruction by penetrating keratoplasty or anterior lamellar graft keratoplasty, which seems to lead to satisfactory results [14]. To our knowledge, pharmacological treatments, including topical treatments, are not effective for this kind of lesion.

In ophthalmology, myxomas have also been reported in the conjunctiva, in the orbit, and under the eyelid. In the conjunctiva, lesions are always isolated, while up to 15% of myxomas under the eyelid are associated with Carney complex. This is an autosomal dominant genetic disorder, which associates cardiac myxomas, lentigines, naevi, Cushing’s syndrome, acromegaly, and mucous pigmentation, which can affect the conjunctiva [3,4,6,7]. The major risk is a cardiac myxoma, which can be worsened by emboli, heart failure, or arrhythmia. Therefore, any diagnostic of ocular myxoma should lead to cardiac examination.

Conclusions

Corneal myxomas are rare lesions, often secondary to trauma in the Bowman’s membrane, which is why it is often called a myxomatous corneal degeneration. In this instance, there is no link with Carney complex. However, myxomas under the eyelid or within the orbit are often associated with cardiac myxomas. Treatment is strictly surgical, either by simple excision or by surgical excision followed by graft DMEK. To the best of our knowledge, this is the first time that such an association between DMEK and secondary corneal myxoma has been described in the literature.