Grand Rounds at the New England Eye Center

Woman presents with ocular pain, redness and photophobia

Exam reveals a corneal epithelial defect with surrounding edema and Descemet's folds, and a dense white ring infiltrate.

A 40-year-old woman with a medical history of acute myeloid leukemia treated with bone marrow transplant, complicated by ocular graft-versus-host disease and penetrating keratoplasty in the right eye, urgently presented to the New England Eye Center at Tufts Medical Center due to left ocular pain, redness and photophobia.

Initially, the patient presented with 3 weeks of pain, redness and light sensitivity in the right eye when she stopped using loteprednol in that eye. The left eye was asymptomatic. Vision in both eyes was at baseline. The patient was prescribed prednisolone acetate 1% taper, artificial tears and ointment in the right eye.

However, 1 week later, she returned with decreased vision, severe pain and photophobia in the left eye. Pain and redness in the right eye had resolved. She was followed closely over the next 2 weeks and had worsening vision, persistent pain and photophobia in the left eye.

large epithelial defect and ring infiltrate
Figure 1. Slit lamp photos of the left eye demonstrating a large epithelial defect and ring infiltrate.

Source: Christine L. Shen, MD, and Helen K. Wu, MD

The patient reported swimming in a lake once in the past several weeks. She did not wear glasses or contact lenses. She had no history of cold sores. She had been lost to follow-up to her primary care physician and oncologist but reported being in remission from acute myeloid leukemia. She also had a history of bipolar disorder and untreated hepatitis C. She had no family history of eye disease. She had no history of smoking, drinking alcohol or using illicit drugs. Review of systems was negative except as noted above.

Examination

The patient’s visual acuity on initial presentation was counting fingers in the right eye and 20/20 in the left eye. Pupils were symmetric with no afferent pupillary defect. IOPs were 13 mm Hg and 12 mm Hg in the right and left eyes, respectively. On anterior segment exam, the right eye was noted to have diffuse neovascularization over the PK graft with 2+ diffuse superficial punctate keratitis. The left eye had no abnormalities. Fundus exam was unremarkable.

HRT confocal images
Figure 2. HRT confocal images of the left eye demonstrating diffuse inflammatory cells and decreased nerve density.

At 1-week follow-up, the patient’s visual acuity was stable in the right eye but had decreased to 20/70 in the left eye. Her anterior exam was notable for diffuse conjunctival injection and chemosis in the left eye. A new central, oval-shaped corneal epithelial defect had also developed in the left eye, measuring 20% of the total corneal area with surrounding stromal edema and Descemet’s folds. There was 2+ anterior chamber cell present with no hypopyon. Corneal sensation testing was 0 over the epithelial defect and 6 superiorly. On subsequent exams over the next few weeks, visual acuity progressively decreased to hand motion in the left eye. The corneal epithelial defect in the left eye enlarged to cover 90% of the total corneal area (8 mm to 9 mm in height and width), sparing the superior 1 mm. She also developed a dense white ring infiltrate spanning 360° but most prominent from 4 to 11 o’clock (Figure 1). Exam of the right eye remained unchanged.

Heidelberg Retina Tomograph (HRT) confocal imaging of the left eye demonstrated nonspecific inflammatory cells and decreased nerve density (Figure 2).

What is your diagnosis?

See answer on next page.

Ring keratitis

The differential diagnosis of ring keratitis includes infectious keratitis related to gram-negative bacteria, Acanthamoeba, herpes simplex virus and fungus, as well neurotrophic keratitis. Recurrence of ocular graft-versus-host disease was also considered in our patient. Infectious workup included corneal cultures of the left eye, which were negative for bacteria, Acanthamoeba, mycobacteria and fungus. HSV-1 and HSV-2 PCR of the cornea was negative. HRT confocal microscopy may demonstrate double-walled cysts in Acanthamoeba infection or hyphae in fungal infection; however, the patient’s confocal images showed nonspecific inflammation. After exclusion of infectious etiology, further history was obtained and the patient finally admitted to frequent use of topical anesthetics. There was noted clinical improvement after cessation of anesthetic drops, and thus, the patient was diagnosed with toxic keratopathy from topical anesthetic abuse.

Discussion

Topical anesthetic abuse can present as a nonhealing corneal epithelial defect with peripheral ring infiltrate. While topical anesthetics are safely used in the office setting for testing purposes, chronic frequent use can precipitate corneal melting and permanent vision loss. In three case series of patients with topical anesthetic abuse keratopathy, almost all subjects were men in their 30s who sustained initial injury from a metallic foreign body or from ultraviolet keratitis. These studies also reported an association with psychiatric disorders in this population, including major depressive disorder, substance abuse and personality disorders. Other case reports of topical anesthetic abuse keratitis occurred in patients after laser refractive surgery. Patients obtain topical anesthetics from physicians who prescribed the medication, at pharmacies and by surreptitiously taking bottles from eye clinics. Some studies by emergency room physicians argue that a short course of topical anesthetics following corneal abrasions has not been shown to cause delayed healing or adverse outcomes. However, most ophthalmologists advise against prescribing topical anesthetics to patients.

Early topical anesthetic abuse presents as punctate epithelial keratitis. With continued use of anesthetics, the punctate areas can become confluent, forming a large circular persistent epithelial defect with stromal edema and haze. A peripheral ring infiltrate develops around the epithelial defect and often raises the suspicion for Acanthamoeba keratitis, especially when the patient demonstrates pain out of proportion to findings on exam. Robust anterior chamber inflammation can occur with keratic precipitates and hypopyon. Corneal endothelial cell damage has been noted as well. Topical anesthetics can cause damage to the corneal nerves, resulting in neurotrophic keratitis.

Diagnosis is often made only after patients admit to or are discovered using topical anesthetics. Infectious etiologies must be ruled out with corneal cultures for Acanthamoeba, fungus, HSV, bacteria and mycobacteria. Confocal images can assist with identifying Acanthamoeba cysts or fungal hyphae. Often, the diagnosis is made once the patient admits to topical anesthetic abuse or is found using the medication. Admission is frequently required both to closely monitor the patient and for adequate pain control. Even with the diagnosis of toxic keratitis, cultures should be obtained to evaluate for secondary bacterial superinfection.

Once topical anesthetic abuse is determined, the most important treatment is stopping these medications. It is important to establish a good rapport because patients become reliant on the topical anesthetics to treat ocular pain. Topical antibiotics are used to prevent secondary infection while epithelial defects are present. Serum tears or amniotic membrane placement can be used to promote epithelial regrowth. If permanent corneal scarring occurs, penetrating keratoplasty may be beneficial. Pressure patching the eye with antibiotic ointment can both decrease pain and prevent the patient from administering harmful medications. If neuropathic pain is suspected, the patient may be prescribed tricyclic antidepressants, gabapentin or low-dose naltrexone. Unfortunately, some patients do not regain vision and require enucleation for severe pain.

Clinical course continued

The patient was admitted for fortified topical antibiotics. She was also treated for possible HSV-related neurotrophic keratitis. The epithelial defect did not improve despite this therapy. During her admission, she admitted to using proparacaine drops over the last several weeks and was found to have topical lidocaine gel in her belongings. At this point, fortified topical antibiotics were discontinued. The patient was instructed to pressure patch the left eye with erythromycin ointment. She was then closely monitored to prevent further topical anesthetic abuse. The corneal epithelial defect in the left eye decreased to 5 mm in height by 7 mm in width at the time of discharge a few days later. She continued to have significant ocular pain in both eyes and was prescribed pregabalin and low-dose naltrexone for treatment of neuropathic pain. At a follow-up visit 8 weeks after initial presentation, the epithelial defect had resolved with residual inferior stromal scarring. The dense white infiltrate had resolved.

A 40-year-old woman with a medical history of acute myeloid leukemia treated with bone marrow transplant, complicated by ocular graft-versus-host disease and penetrating keratoplasty in the right eye, urgently presented to the New England Eye Center at Tufts Medical Center due to left ocular pain, redness and photophobia.

Initially, the patient presented with 3 weeks of pain, redness and light sensitivity in the right eye when she stopped using loteprednol in that eye. The left eye was asymptomatic. Vision in both eyes was at baseline. The patient was prescribed prednisolone acetate 1% taper, artificial tears and ointment in the right eye.

However, 1 week later, she returned with decreased vision, severe pain and photophobia in the left eye. Pain and redness in the right eye had resolved. She was followed closely over the next 2 weeks and had worsening vision, persistent pain and photophobia in the left eye.

large epithelial defect and ring infiltrate
Figure 1. Slit lamp photos of the left eye demonstrating a large epithelial defect and ring infiltrate.

Source: Christine L. Shen, MD, and Helen K. Wu, MD

The patient reported swimming in a lake once in the past several weeks. She did not wear glasses or contact lenses. She had no history of cold sores. She had been lost to follow-up to her primary care physician and oncologist but reported being in remission from acute myeloid leukemia. She also had a history of bipolar disorder and untreated hepatitis C. She had no family history of eye disease. She had no history of smoking, drinking alcohol or using illicit drugs. Review of systems was negative except as noted above.

Examination

The patient’s visual acuity on initial presentation was counting fingers in the right eye and 20/20 in the left eye. Pupils were symmetric with no afferent pupillary defect. IOPs were 13 mm Hg and 12 mm Hg in the right and left eyes, respectively. On anterior segment exam, the right eye was noted to have diffuse neovascularization over the PK graft with 2+ diffuse superficial punctate keratitis. The left eye had no abnormalities. Fundus exam was unremarkable.

HRT confocal images
Figure 2. HRT confocal images of the left eye demonstrating diffuse inflammatory cells and decreased nerve density.

At 1-week follow-up, the patient’s visual acuity was stable in the right eye but had decreased to 20/70 in the left eye. Her anterior exam was notable for diffuse conjunctival injection and chemosis in the left eye. A new central, oval-shaped corneal epithelial defect had also developed in the left eye, measuring 20% of the total corneal area with surrounding stromal edema and Descemet’s folds. There was 2+ anterior chamber cell present with no hypopyon. Corneal sensation testing was 0 over the epithelial defect and 6 superiorly. On subsequent exams over the next few weeks, visual acuity progressively decreased to hand motion in the left eye. The corneal epithelial defect in the left eye enlarged to cover 90% of the total corneal area (8 mm to 9 mm in height and width), sparing the superior 1 mm. She also developed a dense white ring infiltrate spanning 360° but most prominent from 4 to 11 o’clock (Figure 1). Exam of the right eye remained unchanged.

Heidelberg Retina Tomograph (HRT) confocal imaging of the left eye demonstrated nonspecific inflammatory cells and decreased nerve density (Figure 2).

What is your diagnosis?

See answer on next page.

PAGE BREAK

Ring keratitis

The differential diagnosis of ring keratitis includes infectious keratitis related to gram-negative bacteria, Acanthamoeba, herpes simplex virus and fungus, as well neurotrophic keratitis. Recurrence of ocular graft-versus-host disease was also considered in our patient. Infectious workup included corneal cultures of the left eye, which were negative for bacteria, Acanthamoeba, mycobacteria and fungus. HSV-1 and HSV-2 PCR of the cornea was negative. HRT confocal microscopy may demonstrate double-walled cysts in Acanthamoeba infection or hyphae in fungal infection; however, the patient’s confocal images showed nonspecific inflammation. After exclusion of infectious etiology, further history was obtained and the patient finally admitted to frequent use of topical anesthetics. There was noted clinical improvement after cessation of anesthetic drops, and thus, the patient was diagnosed with toxic keratopathy from topical anesthetic abuse.

Discussion

Topical anesthetic abuse can present as a nonhealing corneal epithelial defect with peripheral ring infiltrate. While topical anesthetics are safely used in the office setting for testing purposes, chronic frequent use can precipitate corneal melting and permanent vision loss. In three case series of patients with topical anesthetic abuse keratopathy, almost all subjects were men in their 30s who sustained initial injury from a metallic foreign body or from ultraviolet keratitis. These studies also reported an association with psychiatric disorders in this population, including major depressive disorder, substance abuse and personality disorders. Other case reports of topical anesthetic abuse keratitis occurred in patients after laser refractive surgery. Patients obtain topical anesthetics from physicians who prescribed the medication, at pharmacies and by surreptitiously taking bottles from eye clinics. Some studies by emergency room physicians argue that a short course of topical anesthetics following corneal abrasions has not been shown to cause delayed healing or adverse outcomes. However, most ophthalmologists advise against prescribing topical anesthetics to patients.

Early topical anesthetic abuse presents as punctate epithelial keratitis. With continued use of anesthetics, the punctate areas can become confluent, forming a large circular persistent epithelial defect with stromal edema and haze. A peripheral ring infiltrate develops around the epithelial defect and often raises the suspicion for Acanthamoeba keratitis, especially when the patient demonstrates pain out of proportion to findings on exam. Robust anterior chamber inflammation can occur with keratic precipitates and hypopyon. Corneal endothelial cell damage has been noted as well. Topical anesthetics can cause damage to the corneal nerves, resulting in neurotrophic keratitis.

PAGE BREAK

Diagnosis is often made only after patients admit to or are discovered using topical anesthetics. Infectious etiologies must be ruled out with corneal cultures for Acanthamoeba, fungus, HSV, bacteria and mycobacteria. Confocal images can assist with identifying Acanthamoeba cysts or fungal hyphae. Often, the diagnosis is made once the patient admits to topical anesthetic abuse or is found using the medication. Admission is frequently required both to closely monitor the patient and for adequate pain control. Even with the diagnosis of toxic keratitis, cultures should be obtained to evaluate for secondary bacterial superinfection.

Once topical anesthetic abuse is determined, the most important treatment is stopping these medications. It is important to establish a good rapport because patients become reliant on the topical anesthetics to treat ocular pain. Topical antibiotics are used to prevent secondary infection while epithelial defects are present. Serum tears or amniotic membrane placement can be used to promote epithelial regrowth. If permanent corneal scarring occurs, penetrating keratoplasty may be beneficial. Pressure patching the eye with antibiotic ointment can both decrease pain and prevent the patient from administering harmful medications. If neuropathic pain is suspected, the patient may be prescribed tricyclic antidepressants, gabapentin or low-dose naltrexone. Unfortunately, some patients do not regain vision and require enucleation for severe pain.

Clinical course continued

The patient was admitted for fortified topical antibiotics. She was also treated for possible HSV-related neurotrophic keratitis. The epithelial defect did not improve despite this therapy. During her admission, she admitted to using proparacaine drops over the last several weeks and was found to have topical lidocaine gel in her belongings. At this point, fortified topical antibiotics were discontinued. The patient was instructed to pressure patch the left eye with erythromycin ointment. She was then closely monitored to prevent further topical anesthetic abuse. The corneal epithelial defect in the left eye decreased to 5 mm in height by 7 mm in width at the time of discharge a few days later. She continued to have significant ocular pain in both eyes and was prescribed pregabalin and low-dose naltrexone for treatment of neuropathic pain. At a follow-up visit 8 weeks after initial presentation, the epithelial defect had resolved with residual inferior stromal scarring. The dense white infiltrate had resolved.