Late-Onset Chronic Corneal Fistula Following Phototherapeutic Keratectomy: A Case Report and Importance of Early Detection

Background

Corneal fistula is a rare clinical finding that can occur during the corneal healing process and can be easily missed. It is defined as an abnormal communication between the anterior chamber and the corneal surface, which often fails to heal due to continuous flow of aqueous humor and an imperfect apposition between the internal and external surfaces [1]. In cases where a corneal fistula goes unnoticed, various complications can arise, including hypotony, anterior synechiae, and endophthalmitis [1]. We report a rare finding of positive Seidel test in a decompensated cornea with previous multiple surgeries and a recent phototherapeutic keratectomy (PTK). We provide a mechanistic explanation of the possible etiopatho-genesis of this presentation and highlight the essential role of anterior segment optical coherence tomography (AS-OCT) in the assessment of similar cases.

Case Report

A 73-year-old female patient, with asthma, hypertension, and ischemic heart disease presented for routine follow-up at King Khaled Eye Specialist Hospital (KKESH) as a case of bilateral chronic angle closure glaucoma and painful bullous keratopathy in the left eye.

Her past surgical history included an uneventful phacoemulsification cataract surgery in the right eye, and a combined trabeculectomy and phacoemulsification cataract surgery in the left eye. Surgery in the left eye was complicated by a posterior capsular tear and was converted to an extracapsular cataract extraction (ECCE) and anterior vitrectomy. A few months postoperatively, the patient had chronic pain and redness of the left eye, secondary to a decompensated cornea.

Given the advanced stage of glaucoma with guarded visual potential in the diseased eye, the patient underwent alternative palliative treatments to posterior lamellar keratoplasty including: PTK in 2012 (ablation depth: 120 μm, optical and transition zones: 6.00 and 8.00 mm, respectively) (VISX STAR S4-IR WaveScan excimer laser; Johnson and Johnson, Inc., New Brunswick, NJ, USA); stromal puncture with amniotic membrane transplant (AMT) in 2016; and a second deeper PTK with amniotic membrane transplant in 2019 due to persistence of symptoms and recurrence of corneal erosions and bullae (ablation depth: 200 μm, optical and transition zones: 6.00 and 8.00 mm, respectively) (Schwind Amaris 750 excimer laser; SCHWIND eye-tech-solutions GmbH, Kleinostheim, Germany).

Three years after her most recent PTK (2019), she presented for a regular follow-up at the cornea clinic, when a pinpoint cor-neal leak was noted on fluorescein staining of the left cornea.

Her corrected distance visual acuity was 20/40 in the right eye and hand motion in the left eye. Intraocular pressure (IOP) was 18 and 40 mmHg. Slit lamp examination (SLE) of the left eye showed a diffusely scarred cornea, peripheral corneal neovascularization, superficial punctate keratitis, and a paracentral area of slowly appearing, spontaneous, pinpoint corneal leak (Figure 1A–1C, Video 1) with an underlying intrastromal fluid pocket (lacunae). The anterior chamber was formed and there was no corneal epithelial defect. A multipiece posterior chamber intraocular lens (IOL) was well positioned in the sulcus, and the iris was normal except for a superior iridectomy. B-scan ultrasonography of the posterior pole indicated a flat retina with large optic disc cupping. Examination of the right eye was unremarkable.

AS-OCT of the left eye, showed a diffuse anterior stromal hyper-reflectivity corresponding to postoperative scarring, in addition to an area of intrastromal hypo-reflectivity at the inferior paracentral cornea and an irregular Descemet membrane (DM) with areas of discontinuity (Figure 1D, 1E).

A thin layer of n-Butyl-2 cyanoacrylate glue (Histoacryl, H.B. Fuller, Ann Arbor, MI, USA) was applied over the leaking area followed by bandage contact lens placement. The patient was started on topical moxifloxacin 0.5% QID (Vigamox, Alcon Laboratories Inc., Geneva, Switzerland), in addition to 3 topical glaucoma drops: dorzolamide 2% TID (Trusopt 2% eye drops, Merck & Co., Inc., Rahway, NJ, USA); brimonidine tartrate 0.15% TID (Alphagan P; Allergan, Inc., Dublin, Ireland); bimatoprost 0.01% qhs (Lumigan RC, Allergan, Inc., Dublin, Ireland).

Postoperatively, a thin layer of glue was well attached with no leak on Seidel test (Figure 2A, 2B). Intraocular pressure was digitally normal with a visual acuity of hand motion. Eight weeks later, a clinical exam showed a well-apposed thin layer of glue with no evidence of leak. The previously noted intrastromal fluid collection was resolved, but an area of inferior Descemet membrane detachment was noted with the aid of AS-OCT (Figure 2C). IOP was 28 mmHg, for which the patient was started on an oral ocular hypotensive agent (acetazolamide, 500 mg BID) and referred to the glaucoma service for optimum control of IOP. At the latest follow-up visit, the Descemet membrane had spontaneously reattached, IOP was well controlled, and there was no corneal leak (Figure 2D).

Discussion

Pseudophakic bullous keratopathy (PBK) is a postoperative corneal disease characterized by the development of irreversible corneal edema, secondary to endothelial trauma during cataract surgery. The corneal endothelial layer has Na-K-ATPase pumps that ensure the cornea is relatively dehydrated and transparent [2]. Intraoperative trauma that occurs from surgical instruments and endothelial burns resulting from high power during phacoemulsification can lead to permanent endothelial injury and subsequent loss of pump function. Studies have shown abnormalities of water channel proteins (AQPs) in PBK, mainly decreased AQP1, and increased AQP3 and AQP4 [3]. This leads to chronic corneal edema that occurs initially in the corneal stroma, and extends subsequently to involve the epithelium, forming bullae.

Managing PBK is challenging and can include medical and surgical interventions. Initial medical management consists of using hyperosmotic agents, lubricants, aqueous suppressants drugs, steroids and contact lenses [2].

In advanced cases, various surgical approaches are available depending upon the severity, the visual potential, and availability of keratoplasty. This includes Gunderson conjunctival flap, amniotic membrane grafting, anterior stromal puncture, corneal crosslinking, and PTK [2,4].

In an eye with good visual potential, a posterior lamellar or endothelial keratoplasty remains the criterion standard treatment, but it was discouraged in the reported case due to poor visual potential in the setting of end-stage glaucoma. A Gunderson conjunctival flap could have been used as an effective method to alleviate our patient’s bullous keratopathy symptoms, but it was not performed given her previous history of superior trabeculectomy and the possible need for a future glaucoma procedure where a healthy conjunctiva may be necessary. Moreover, given the uncontrolled intraocular pressure at presentation, a conjunctival flap could compromise the penetration and effectiveness of required topical anti-glaucoma medications.

Previous studies of PTK with an argon fluoride (ArF) excimer laser have reported effective long-term pain relief in 70% of treated patients with painful PBK, with]5[or without amniotic membrane transplant [6]. PTK works by ablating the superficial surface of the cornea, including the abnormal basement membrane [7[, as well as the preterminal neural plexus deep to Bowman’s membrane [6]. This laser is extremely precise in ablating 0.25 µm of tissue with a single pulse [8]. This would reduce the pain and promote corneal scarring, which stabilizes the epithelium and reduces the corneal edema [9]. Different ablation depths of PTK have been attempted for treating painful bullous keratopathy, and deep ablation (25% stromal thickness) seems to result in the best outcomes [6]. The procedure can be repeated if necessary, provided there is adequate corneal thickness [9]. Complications of PTK include infection, delayed healing of the epithelium, reactivation of herpes simplex virus, and recurrence of bullous keratopathy [8,10].

AS-OCT is a noninvasive noncontact imaging technique that enables detailed assessment of the corneal layers and provides strong clues to histological findings. Since its introduction to clinical practice, AS-OCT has allowed ophthalmologists to better assess various corneal and anterior segment pathologies [11].

Corneal fistula is a rare clinical finding, which was defined by Mannis et al as a chronic communication between the anterior chamber (AC) and the corneal surface [12]. An open fistula is a track through which aqueous humor has access to the corneal surface and tear film. A closed fistula has a similar track, but is closed at the external end with no access to the tear film. Corneal fistula has been described in some corneal conditions, including keratoconus with hydrops [13] and following a healed keratitis [1].

AlMaazmi et al evaluated fluid leaks in non-traumatic corneal perforations and they observed 2 mechanisms [14]. The first group (indirect leak) showed a formed AC, epithelial bullae, hydration of the corneal stroma, intrastromal accumulation of fluid in pockets (seen as dark hyporeflective spaces), and a lamellar separation of the stroma demonstrated by AS-OCT. This group of cases shared an indirect communication between the AC and the exterior of the cornea where the stromal lamellae acted like a valve, slowing the leak of aqueous humor and maintaining a formed AC. In contrast, the second group (direct leak) had a short and direct communication between the AC and the corneal surface and presented with a brisk leak and a shallow AC. We believe that our case falls under the group of indirect leaks, where Descemet’s membrane separation was also more often encountered [14].

Total ultrasound energy ]15[and preoperative nuclear firmness ]16,17[were reported as major intraoperative mechanical factors correlating with postoperative endothelial trauma and loss of endothelial cell density. Non-complicated cataract surgery has been observed to induce a 10-year endothelial cell loss rate of up to 20% ]17[, and this rate is expected to increase in an event of a complicated cataract surgery. Given a history of complicated cataract surgery converted to ECCE in the presented eye, potential source of endothelial damage includes the direct trauma to the endothelium by lens fragments and turbulent fluidics.

Bowman’s layer (BL) is highly resistant to penetration or damage, and provides tectonic support for the cornea [18]. Histopathological studies of PBK report breaking and loss of BL in diseased cornea [19]. Additionally, repeated sessions of PTK in the same patient can result in further damage and loss of Bowman’s layer [7]. We hypothesize that the mechanism involved in our patient was the presence of a weak endothelium with areas of discontinuity, which served as an entry point on the internal surface of an indirect fistula. This, coupled with the presence of uncontrolled intraocular pressure, allowed a slow inflow of aqueous humor into the stroma, where fluid was accumulating in intrastromal potential cystic spaces bounded anteriorly by the epithelium. The disturbance of the anterior stroma, including the Bowman’s layer after deep PTK, with loosely arranged and poorly apposed stromal tissue secondary to chronic PBK, resulted in anterior stromal weakness and allowed for a slow seep of fluid to the external corneal surface through a defective area during the healing process.

Although chronic slow fistulas can initially be managed conservatively with bandage contact lens and aqueous suppressants, we elected to apply cyanoacrylate gluing for this case, as patient compliance with close follow-p was not assured due to social reasons.

Conclusions

This report presents an uncommon finding of a non-traumatic corneal leak in a decompensated cornea in its healing process after multiple previous surgeries and a recent PTK. Our observations provide a mechanistic explanation of possible etiopatho-genesis behind this presentation and highlights the essential role of AS-OCT in assessing the corneal findings. Similar subtle leaks in the setting of a formed anterior chamber are often missed and carry a risk of infection. Keen observation and a habitual check for leakage using fluorescein stain should be practiced over the long term of compromised corneas during their healing process.