Woman experiences previous ‘gush’ of fluid from right eye, now acute left eye pain
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A 28-year-old Latino woman presented to the University of New Mexico emergency department with the complaint of acute onset left eye pain, photophobia and visual decline.
She described the pain as sharp and constant with a severity of 7 out of 10. Her symptoms occurred abruptly in the middle of the day 1 day prior without any inciting trauma or injury to the eye. She had similar pain in her right eye more than 1 month before presentation and was diagnosed with a corneal abrasion at an outside emergency department. She was subsequently started on erythromycin ointment twice daily and scheduled for outpatient follow-up with an ophthalmologist. About 3 weeks ago, the patient noticed a “gush” of fluid from her right eye with visual decline. Since that event, vision, redness and pain have remained stable in her right eye.
Source: Allison Resnik, MD, and Alexander Davis, MD, PhD
Ocular history was notable for myopia with astigmatism for which she wears glasses. She denied prior or current contact lens wear. Notably, she denied a history of dry eyes, previous ocular infections or ophthalmic surgery. She did not use any ocular medications. The patient was previously healthy; however, over the past 4 months she developed new onset diffuse bilateral joint pain and swelling in which she was seen in and out of the emergency department with subsequent follow-up with a rheumatologist. Laboratory workup revealed leukopenia, anemia and thrombocytopenia. Inflammatory markers were elevated with a sed rate of 120 and C-reactive protein of 5.3. Antinuclear antibody was positive with a titer of 1:1280 with a homogenous pattern. Rheumatoid factor was elevated to 81. She was started on oral prednisone for these findings with improvement in her symptoms and was currently being tapered off the steroid. Her only medication was 10 mg of oral prednisone. Socially, she denied any tobacco or drug use and drank alcohol socially.
Examination
Visual acuity was 20/100 in the right eye and 20/150 in the left eye without spectacle correction. With pinhole, visual acuity improved in the right eye to 20/80-1 with no improvement in the left eye. IOP was 13 mm Hg in both eyes measured via iCare tonometry. The pupil in the right eye was irregular and nonreactive. The pupil in the left eye was round and reactive. Slit lamp exam of both eyes can be seen in Figure 1. The right eye revealed diffuse trace conjunctival injection with a paracentral corneal perforation at 5 o’clock with incarcerated iris, overlying epithelial growth and surrounding epithelial cysts with associated stromal haze. The anterior chamber was formed without cell, flare or hypopyon. The vitreous had no evidence of cells in either eye. The left eye revealed a central area of corneal depression with fluorescein staining and 20% corneal thinning encroaching on the visual axis with associated white blood cells clustering near the rolled edges of the area of depression. Dilated fundus exam was deferred for both eyes given the anterior segment findings.
What is your diagnosis?
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Corneal perforation, ulceration
The features of a chronic-appearing corneal perforation in the right eye and new unprovoked corneal ulceration in the left eye in a patient with new onset diffuse joint pain and swelling are most consistent with bilateral corneal melting due to a systemic disease process. Upon recognition of corneal thinning, it is important to rule out an infectious etiology. Other etiologies include trauma, noninfectious inflammatory processes or degenerative processes. However, in our patient, the highest on our differential was a systemic autoimmune disease contributing to bilateral corneal thinning.
Management
To better assess the extent of corneal thinning and develop a surgical plan, anterior segment OCT (AS-OCT) can be used. This confirmed perforation with iris incarceration in the right eye with overlying epithelial growth and adjacent significant corneal thinning (Figure 2a). The left eye demonstrated focal hyperreflectivity around the corneal ulceration with infiltration with inflammatory cells (Figure 2b).
The patient was started on topical moxifloxacin four times a day in both eyes and aggressive lubrication with artificial tears in the left eye. Systemically, she was instructed to increase her oral steroids and started on oral doxycycline and vitamin C. She was taken to the operating room later that week, and a full-thickness corneal patch graft was performed with overlying amniotic membrane and bandage contact lens.
The ophthalmic findings were communicated to the patient’s rheumatologist, prompting further laboratory workup. Additional labs demonstrated positive anti-Ro/SSA and anti-La/SSB, negative anti-cyclic citrullinated peptide and other testing negative for specific autoimmune markers. A CT scan was also performed and demonstrated parotid gland enhancement on the right side. The patient has presently received a diagnosis of undifferentiated connective tissue disease, attributed to the diverse serological and clinical manifestations of a systemic autoimmune condition. Treatment was initiated with high-dose systemic methotrexate and supplemental folate.
Discussion
Corneal perforations are ocular emergencies and characterized by full-thickness tissue loss in the cornea. These can occur from a variety of etiologies, and determining the cause is of vital importance for proper management.
Patients with corneal perforations may present with a decline in visual acuity, eye redness, mild pain, and increased leakage or a “gush” of fluid from the eye. They may report inciting trauma or recent infection or surgery. On clinical examination, there is typically a decline in visual acuity and low/normal IOP with an irregular pupil. Slit lamp examination may demonstrate conjunctival injection and flattening of the anterior chamber with a perforation site that may be acutely demonstrating aqueous leakage or may have iris incarcerated and plugging the perforation. For all corneal perforations, inspection of the other eye is vital, especially in nontraumatic cases, to further determine the underlying cause. In our case, finding evidence of corneal thinning in the left eye in a similar location where the perforation occurred in the right eye pointed us toward an inflammatory-mediated systemic process.
Once a corneal perforation is diagnosed, it is important to treat the underlying etiology and reconstitute the globe. Causes of corneal perforation can be classified into different categories such as trauma, iatrogenic, infectious or noninfectious keratitis, degenerative disorders or dystrophies. Specifically, in our case, there were a few findings that assisted us in narrowing down the etiology and managing further workup. First, this patient was found to have a self-sealing corneal perforation in the right eye that has been present for presumably 3 weeks, which raises high suspicion for a neurotrophic component. Additionally, she was found to have an irregular corneal ulceration in the left eye without preceding trauma or event. Given the presumed bilateral involvement, there was a high concern for a systemic process. On review of systems, the patient reported a 4-month history of bilateral joint pain and swelling for which she saw a rheumatologist and was started on oral prednisone.
After a cause is determined, medical treatments can be instituted to help optimize healing. If an autoimmune etiology is suspected, a systemic workup should be conducted, and systemic steroid therapy should be instituted. If the perforation was precipitated from an infectious ulcer, cultures should be obtained, and the patient should be started on aggressive topical antibiotics. Once the causative organism is determined, targeted antibiotics can be instituted. Lastly, if degeneration of the cornea is thought to be due to severe ocular surface disease, it is vital to institute ocular lubricating therapy. This can include lubricating eye drops and ointment, punctal occlusion with punctal plugs or cautery, placing a bandage contact lens or amniotic membrane, and autologous serum tears. In our patient, we were highly suspicious for a systemic process, thus prompting an increase in systemic steroids. Additionally, topical antibiotics were instituted to prevent infection in the setting of active ulceration. Lastly, aggressive lubrication of the left eye was instituted to help prevent further corneal thinning. Regardless of etiology, it is vital to institute therapy to promote corneal healing. Some providers argue that patients with corneal ulceration should be started on oral doxycycline and oral vitamin C to help facilitate the healing process. Doxycycline has been proven to inhibit collagenase and matrix metalloproteinases, and vitamin C facilitates collagen synthesis.
The pathophysiology behind corneal ulceration in autoimmune conditions is not fully understood. However, it is theorized that it is due to a combination of a poor ocular surface environment with an unregulated immune response against the body’s own antigens, which results in release of inflammatory cytokines and epithelial breakdown of the ocular surface. Chronic persistent epithelial destruction can stimulate infiltration of the corneal stroma by inflammatory cells and cause lysosomal enzymatic degradation of collagen and ground substance by collagenase and other proteases. This stimulation of collagenase production by corneal fibroblasts or stromal keratocytes may further contribute to stromal degradation. When the process infiltrates deep stroma, Descemet’s membrane may be exposed, opening an avenue for it to protrude anteriorly and form a descemetocele. Once a descemetocele is formed, any minor trauma or Valsalva maneuver can cause rupture of Descemet’s membrane, leading to a full-thickness corneal perforation. Reflecting on our case, we suspect the patient was likely having progressive corneal thinning in the right eye that was initially being treated by the emergency department as a corneal abrasion. When she was last seen and diagnosed with a “corneal cyst,” she likely had a descemetocele at that time. The episode in which she described a “gush” of fluid likely represented perforation of the descemetocele. In her case, the iris incarcerated the perforation, which allowed the globe to maintain an anterior chamber and normal IOP. The epithelial overgrowth overlying the iris favors the chronicity since the perforation.
Managing the perforation surgically depends on the size of the perforation and location. Microperforations may seal spontaneously and can be treated with a tight bandage contact lens to tamponade or amniotic membrane graft. Typically, if the perforation is less than 2 mm, it can be sealed with a tissue adhesive or glue. Other options include the use a conjunctival pedicle flap to provide fibrovascular tissue to cover the perforation and restore vital serum growth factors. A variety of grafts may also be used, such as amniotic membrane grafts or patch grafts. If the perforation is peripheral, these temporizing measures may be enough to seal the wound and allow for closure. However, if the perforation is more centrally located, definitive treatment ultimately requires a corneal transplant.
For larger perforations greater than 3 mm, an emergent corneal transplantation is typically indicated. Penetrating keratoplasty is typically the most common procedure performed as it allows for removal of unstable tissue and helps eliminate any active infection. However, in cases in which the systemic process is not fully understood, it may be beneficial to place a temporizing patch graft to reconstitute the globe with plans for a larger keratoplasty in the future once the systemic disease is under better control.
In our case, the perforation measured 3 mm × 5 mm with evidence of surrounding stromal thinning. The decision was made to place a 5 mm × 5 mm patch graft with a multilayer overlying amniotic membrane approach and bandage contact lens. A larger penetrating keratoplasty was deferred given the patient’s systemic condition was not adequately managed and the risk of graft failure was high.
Corneal manifestations can often provide insight into undiagnosed systemic disease processes and may be the first indicator of a systemic condition. Specifically, rheumatological conditions commonly associated with corneal thinning and perforation include rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s disease and granulomatosis with polyangiitis. Corneal melting and perforations associated with a systemic autoimmune disease are ocular emergencies as they typically represent a complex course with a guarded visual prognosis. It is important to immediately start these patients on systemic immunosuppressive treatment in addition to surgical intervention to reconstitute the globe and prevent further corneal melting.
Clinical course continued
Examination 1 month after the full-thickness corneal patch graft was performed in the right eye revealed an intact graft with no evidence of thinning (Figure 3a). Best corrected visual acuity is currently 20/150 in that eye. With regards to the left eye, the use of aggressive lubrication and increased systemic immunosuppression prevented further corneal thinning, and since then, the area of corneal ulceration has healed (Figure 3b). AS-OCT revealed re-epithelization of the previous corneal ulceration with residual stromal scarring (Figure 4). Systemically, the patient is being maintained on high-dose methotrexate with additional prednisone to help bridge with close comanagement between her ophthalmologist and rheumatologist.
- References:
- Deshmukh R, et al. Indian J Ophthalmol. 2020;doi:10.4103/ijo.IJO_1151_19.
- Lekskul M, et al. Cornea. 2000;doi:10.1097/00003226-200005000-00011.
- Ralph RA, et al. Cornea. 2000;doi:10.1097/00003226-200005000-00003.
- Shah R, et al. Exp Eye Res. 2021;doi:10.1016/j.exer.2021.108455.
- Smith VA, et al. Br J Ophthalmol. 2004;doi:10.1136/bjo.2003.025551.
- For more information:
- Edited by Jonathan T. Caranfa, MD, PharmD, and Angell Shi, MD, of New England Eye Center, Tufts University School of Medicine. They can be reached at jcaranfa@tuftsmedicalcenter.org and ashi@tuftsmedicalcenter.org.
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