CASE REPORT
A Case of Corneal Endothelial Dysfunction Due to Coxsackievirus A24 Corneal Endotheliitis After Cataract Surgery Dong Hui Lim, MD, Jaeryung Kim, MD, Jung Hye Lee, MD, Eui-Sang Chung, MD, PhD, and Tae-Young Chung, MD, PhD
Purpose: Corneal endotheliitis causes endothelial decompensation and is associated with significant visual impairment. The goal of this article is to report a case of corneal endotheliitis associated with coxsackievirus A24 infection after cataract surgery in a patient who had no previous symptoms indicative of conjunctivitis.
Methods: A 55-year-old man was admitted for cataract surgery when acute hemorrhagic conjunctivitis was prevalent. Because he did not show any signs of suspected conjunctivitis, the cataract surgery was performed. No intraoperative complications occurred, and he was discharged 1 day after the surgery. Three days later, he visited our clinic with complaints of ocular pain and decreased vision in the left eye. Slit-lamp examination showed corneal stromal edema and mild inflammatory reaction in the anterior chamber. On postoperative day 7, anterior chamber irrigation and viral culture from the aqueous humor sample were performed.
Results: Coxsackievirus A24 was detected in the viral culture. Electron photomicroscopic examination with immunohistochemical staining confirmed the presence of viral antigen. Conclusions: This is the first report of corneal endotheliitis caused by coxsackievirus A24 confirmed by viral antigen detection in the aqueous humor of an affected eye. Key Words: acute hemorrhagic conjunctivitis, cataract surgery, corneal endotheliitis, coxsackievirus A24 (Cornea 2014;33:533–535)
C
orneal endotheliitis is characterized by corneal stromal edema associated with destruction of the endothelium and keratic precipitates.1,2 Herpes simplex virus (HSV),3 varicella zoster virus (VZV),4 cytomegalovirus (CMV),5 or other viruses, including mumps,6 are reported as causative Received for publication September 10, 2013; revision received December 22, 2013; accepted January 20, 2014. Published online ahead of print March 7, 2014. From the Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. The authors have no funding or conflicts of interest to disclose. Reprints: Tae-Young Chung, Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Korea (e-mail: tychung@ skku.edu). Copyright © 2014 by Lippincott Williams & Wilkins
Cornea Volume 33, Number 5, May 2014
organisms. There has been no previous report of corneal endotheliitis caused by coxsackievirus A24 (CA24), whereas CA24 is known to be a common causative agent of acute hemorrhagic conjunctivitis (AHC).7 Thus, we had not been made aware of the clinical course, treatment, or prognosis for CA24-associated endotheliitis. Here, we report a case of corneal endothelial dysfunction due to CA24associated corneal endotheliitis that developed after cataract surgery.
CASE REPORT A 55-year-old man was admitted for cataract surgery during the season of AHC. At admission, his best-corrected visual acuity (BCVA) was 20/40 in the right eye and 20/50 in the left eye. The intraocular pressure (IOP) was 14 mm Hg in both eyes. The preoperative slit-lamp examination was normal except for the cataracts, and the specular microscopic finding showed normal endothelial cell density in both eyes: 2850 cells per square millimeter (right eye) and 2932 cells per square millimeter (left eye). Because he had no symptoms of conjunctivitis, such as conjunctival injection, itching sensation, or conjunctival discharge, phacoemulsification and posterior chamber intraocular lens implantation using 3.0-mm sized clear corneal incision was performed first in the right eye and then 3 days later in the left eye. No suture was placed after the surgery. The surgery was uneventful with no intraoperative complications. One day after cataract surgery in his left eye, the uncorrected visual acuity (UCVA) was 20/20 (right eye) and 20/25 (left eye), and the slit-lamp examination revealed slightly injected conjunctiva with mild anterior chamber reaction in both eyes, which were acceptable as immediate postoperative findings. The patient was discharged with routine postoperative topical antibiotics and steroids. Four days after cataract surgery in his left eye, the patient came to our clinic with complaints of ocular pain and decreased vision in the left eye. The UCVA of his left eye was decreased to 20/125, and the slit-lamp examination showed diffuse corneal stromal edema with Descemet folds and mild anterior chamber reaction (Fig. 1A). Considering the possibility of endophthalmitis, atypical toxic anterior segment syndrome (TASS), or corneal endotheliitis of viral origin, moxifloxacin 0.5% (Vigamox; Alcon, Fort Worth, TX) was started 6 times a day with prednisolone acetate 1% (Pred Forte; Allergan, Irvine, CA) every 1 hour, sodium chloride 5% (Muro 128; Bausch & Lomb, Tampa, FL) every 2 hours, 30 mg oral prednisolone per day (Nisolone Tab; Kukje Pharm, Seongnam, Korea), and 500 mg oral famciclovir (Famciclovir; Smithkline Beecham, Welwyn, UK) 2 times per day. He was observed daily; however, there was no sign of clinical improvement. www.corneajrnl.com |
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Cornea Volume 33, Number 5, May 2014
FIGURE 2. An electron microscope image reveals coxsackievirus A24 (CA24) viral antigens in a normal human fetal lung fibroblast (MRC-5) cell line through an indirect immunofluorescent technique (·200). The CA24 antigen is indicated by bright yellow fluorescence (red arrows) when examined under electron photomicroscopy (EPM).
DISCUSSION
FIGURE 1. A, An anterior segment photograph of the left eye taken on postoperative day 4 shows corneal stromal edema with Descemet folds. B, An anterior segment photograph of the left eye taken 6 months after surgery shows corneal stromal edema with Descemet folds. No improvement is seen compared with the photograph taken on postoperative day 4. Three days after the onset of symptoms (7 days after cataract surgery in his left eye), irrigation and aspiration of the anterior chamber were performed with virus culture and diagnostic polymerase chain reaction (PCR) of the aqueous humor for HSV-1, HSV-2, and VZV. Because other patients and their caregivers, including the patient’s caregivers, had been suffering from AHC when the patient was admitted for cataract surgery, viral culture, including adenoviruses, CA24, and enteroviruses was performed. PCR for HSV-1, HSV-2, and VZV were negative; however, viral particles were observed in viral culture. CA24 infection was confirmed by identification of viral antigens using electron photomicroscopic (EPM) examination of normal human fetal lung fibroblast (MRC-5) and human epidermoid carcinoma (Hep-2) cell lines through an indirect immunofluorescent technique using Light Diagnostics (EMD Millipore, Billerica, MA) (Fig. 2). The above-mentioned treatment regimen was continued for 1 month. However, neither the visual impairments nor the corneal edema showed improvement after 6 months (Fig. 1B). The BCVA was 20/200 in the left eye, and the endothelial cell count was not measured by specular microscopy because of severe corneal edema. Keratoplasty was recommended to restore vision, but the patient refused to receive the surgery.
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This is the first case of CA24-associated endotheliitis confirmed by viral culture from an aqueous humor sample. CA24 belongs to the enterovirus genus and consists of an icosahedral capsid made up of 4 structural proteins (VP1, VP2, VP3, and VP4).8 The outbreak of AHC in Korea was caused by CA24, which, together with adenoviruses and enterovirus70, comprises the major group of etiological agents involved in AHC outbreaks worldwide.9 The patient did not present any preoperative or immediate postoperative symptoms of AHC after the cataract surgery, although it was an endemic period of AHC. Corneal endotheliitis developed 4 days after the surgery, and CA24 was detected in the aqueous humor by anterior chamber paracentesis. Isolation of the causative virus in cell culture gives a definitive diagnosis of viral infection. In the case of corneal endotheliitis, detection of virus from corneal endothelium is an ideal method for diagnosis; however, it is practically difficult to obtain corneal endothelial tissue if the patient is not undergoing keratoplasty. Several previous reports suggested that viral detection in the aqueous humor helps the diagnosis of corneal endotheliitis.3,5,10,11 These reports demonstrated the usefulness of an aqueous humor sample to confirm the virus causative of corneal endotheliitis. In virological investigations using aqueous humor, both viral culture and PCR can be performed. Conventionally, viral culture is considered the gold standard for detecting viral antigen; however, it requires a relatively long time to detect slow-growing viruses. Conversely, PCR is easy to perform, reasonably sensitive, and highly specific for the diagnosis of viral infection.3,5,12 Confocal microscopy is useful in some cases.13,14 For example, an intranuclear inclusion body seen on confocal microscopy is characteristic of CMV infection.13 In this case, anterior chamber paracentesis and viral culture from the aqueous humor with immunostaining were performed. Subsequent EPM examination through an indirect 2014 Lippincott Williams & Wilkins
Cornea Volume 33, Number 5, May 2014
immunofluorescent technique using a monoclonal antibody detected CA24. There have been previous reports of corneal endotheliitis diagnosed by viral culture from an aqueous humor sample. Robin et al10 detected HSV type 1 antigen in cells from the anterior chamber of a patient with corneal endotheliitis in 1985. Madhavan et al11 detected a kind of vesicular virus (family Rhabdoviridae) in the aqueous humor of a patient with corneal endotheliitis by electron microscopy. However, to the best of our knowledge, CA24 has never been reported as a causative virus of corneal endotheliitis by either viral culture or PCR from aqueous humor. At present, the source of the CA24 infection causing corneal endotheliitis is unclear. If the origin were from solutions or instruments contaminated during the cataract surgery, it is expected that widely spread AHC or CA24 endotheliitis in contemporary patients who underwent cataract surgery, would occur because of extremely high contagiousness of CA24. However, other patients who underwent surgeries with the same instruments in the same operating room on the same day presented no abnormal postoperative findings. Therefore, the possibility of CA24 infection during the surgical procedure seems to be very low. Then, the possibility of contamination by CA24 inoculated in the conjunctival or corneal surface without clinical manifestations should be considered. Endotheliitis is not developed by viral infection only but by immune-mediated response. Khodadoust et al2 proposed an autoimmune mechanism acting against the corneal endothelium to be the etiology of corneal endotheliitis in 1982. They reported 2 cases of bilateral corneal endotheliitis that had peripheral corneal edema and linear keratic precipitates, and the presence of inflammatory cells in the anterior chamber and a good response to topical corticosteroids supported their hypothesis about the autoimmune mechanism of corneal endotheliitis. According to Zheng et al,15 an in vivo study of rabbits infected intracamerally with HSV-1 showed that anterior chamber-associated immune deviation due to viral antigen played a pivotal role in corneal endotheliitis development, permitting the virus to invade and damage corneal endothelial cells. The experiment demonstrated that intrastromal inoculation of viral antigen followed by sameeye intracameral viral infection could promote stromal keratitis or keratouveitis, but not corneal endotheliitis. Otherwise, if the fellow eye was intracamerally infected with the virus after inoculation of viral antigen, antigen-specific delayed hypersensitivity was selectively suppressed and showed a specific pattern of inflammation that greatly resembled clinical features of corneal endotheliitis. Herein, we can hypothesize that CA24 viral antigens innoculated in the conjunctival or corneal surface, entered the anterior chamber during the first cataract surgery of the right eye. In AHC, symptoms start after an incubation period of 12–48 hours, and the clinical signs usually disappear in 1–2 weeks.16 The patient underwent cataract surgery first in the right eye and then 3 days later in the left eye, so it could be a latent period for AHC, although no suspicious symptoms or signs for AHC were present at the surgery time. Postoperative first day slit-lamp
2014 Lippincott Williams & Wilkins
A Case of Coxsackievirus A24 Corneal Endotheliitis
examination revealed mild conjunctival injection only without ocular pain, foreign body sensation, irritation, epiphora, photophobia, or subconjunctival hemorrhage, which would seem unlikely in AHC, then the second cataract surgery of the left eye was conducted. At that time, the left eye might have been intracamerally infected with the virus and corneal endotheliitis was occurred by a viral antigen-specific immune mechanism. In conclusion, this is the first case of viral cultureconfirmed CA24-associated corneal endotheliitis of the affected eye after cataract surgery. We suggest that caution might help in the decision to conduct cataract surgery during AHC season, even if the patient does not show any symptoms indicative of conjunctivitis. We would in the future advise avoiding elective ophthalmic surgery on an individual whose family members are afflicted with AHC. The mechanism of corneal endotheliitis caused by the CA24 will require further investigation.
REFERENCES 1. Sutcliffe E, Baum J. Acute idiopathic corneal endotheliitis. Ophthalmology. 1984;91:1161–1165. 2. Khodadoust AA, Attarzadeh A. Presumed autoimmune corneal endotheliopathy. Am J Ophthalmol. 1982;93:718–722. 3. Ohashi Y, Yamamoto S, Nishida K, et al. Demonstration of herpes simplex virus DNA in idiopathic corneal endotheliopathy. Am J Ophthalmol. 1991;112:419–423. 4. Maudgal PC, Missotten L, De Clercq E, et al. Varicella-zoster virus in the human corneal endothelium: a case report. Bull Soc Belge Ophtalmol. 1980;190:71–86. 5. Koizumi N, Yamasaki K, Kawasaki S, et al. Cytomegalovirus in aqueous humor from an eye with corneal endotheliitis. Am J Ophthalmol. 2006; 141:564–565. 6. Singh K, Sodhi PK. Mumps-induced corneal endotheliitis. Cornea 2004; 23:400–402. 7. Yin-Murphy M, Baharuddin-Ishak, Phoon MC, et al. A recent epidemic of Coxsackie virus type A24 acute haemorrhagic conjunctivitis in Singapore. Br J Ophthalmol. 1986;70:869–873. 8. Lévêque N, Amine IL, Cartet G, et al. Two outbreaks of acute hemorrhagic conjunctivitis in Africa due to genotype III coxsackievirus A24 variant. Eur J Clin Microbiol Infect Dis. 2007;26:199–202. 9. Chatterjee S, Quarcoopome CO, Apenteng A. Unusual type of epidemic conjunctivitis in Ghana. Br J Ophthalmol. 1970;54:628–630. 10. Robin JB, Steigner JB, Kaufman HE. Progressive herpetic corneal endotheliitis. Am J Ophthalmol. 1985;100:336–337. 11. Madhavan HN, Goldsmith CS, Rao SK, et al. Isolation of a vesicular virus belonging to the family rhabdoviridae from the aqueous humor of a patient with bilateral corneal endotheliitis. Cornea. 2002;21: 333–335. 12. Yamamoto S, Pavan-Langston D, Kinoshita S, et al. Detecting herpesvirus DNA in uveitis using the polymerase chain reaction. Br J Ophthalmol. 1996;80:465–468. 13. Shiraishi A, Hara Y, Takahashi M, et al. Demonstration of “owl’s eye” morphology by confocal microscopy in a patient with presumed cytomegalovirus corneal endotheliitis. Am J Ophthalmol. 2007;143:715–717. 14. Hillenaar T, Weenen C, Wubbels RJ, et al. Endothelial involvement in herpes simplex virus keratitis: an in vivo confocal microscopy study. Ophthalmology. 2009;116:2077–2086.e1–2. 15. Zheng X, Yamaguchi M, Goto T, et al. Experimental corneal endotheliitis in rabbit. Invest Ophthalmol Vis Sci. 2000;41:377–385. 16. Tavares FN, Costa EV, Oliveira SS, et al. Acute hemorrhagic conjunctivitis and coxsackievirus A24v, Rio de Janeiro, Brazil, 2004. Emerg Infect Dis. 2006;12:495–497.
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A Case of Corneal Endothelial Dysfunction Due to Coxsackievirus A24 Corneal Endotheliitis After Cataract Surgery Dong Hui Lim, MD, Jaeryung Kim, MD, Jung Hye Lee, MD, Eui-Sang Chung, MD, PhD, and Tae-Young Chung, MD, PhD
Purpose: Corneal endotheliitis causes endothelial decompensation and is associated with significant visual impairment. The goal of this article is to report a case of corneal endotheliitis associated with coxsackievirus A24 infection after cataract surgery in a patient who had no previous symptoms indicative of conjunctivitis.
Methods: A 55-year-old man was admitted for cataract surgery when acute hemorrhagic conjunctivitis was prevalent. Because he did not show any signs of suspected conjunctivitis, the cataract surgery was performed. No intraoperative complications occurred, and he was discharged 1 day after the surgery. Three days later, he visited our clinic with complaints of ocular pain and decreased vision in the left eye. Slit-lamp examination showed corneal stromal edema and mild inflammatory reaction in the anterior chamber. On postoperative day 7, anterior chamber irrigation and viral culture from the aqueous humor sample were performed.
Results: Coxsackievirus A24 was detected in the viral culture. Electron photomicroscopic examination with immunohistochemical staining confirmed the presence of viral antigen. Conclusions: This is the first report of corneal endotheliitis caused by coxsackievirus A24 confirmed by viral antigen detection in the aqueous humor of an affected eye. Key Words: acute hemorrhagic conjunctivitis, cataract surgery, corneal endotheliitis, coxsackievirus A24 (Cornea 2014;33:533–535)
C
orneal endotheliitis is characterized by corneal stromal edema associated with destruction of the endothelium and keratic precipitates.1,2 Herpes simplex virus (HSV),3 varicella zoster virus (VZV),4 cytomegalovirus (CMV),5 or other viruses, including mumps,6 are reported as causative Received for publication September 10, 2013; revision received December 22, 2013; accepted January 20, 2014. Published online ahead of print March 7, 2014. From the Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. The authors have no funding or conflicts of interest to disclose. Reprints: Tae-Young Chung, Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Korea (e-mail: tychung@ skku.edu). Copyright © 2014 by Lippincott Williams & Wilkins
Cornea Volume 33, Number 5, May 2014
organisms. There has been no previous report of corneal endotheliitis caused by coxsackievirus A24 (CA24), whereas CA24 is known to be a common causative agent of acute hemorrhagic conjunctivitis (AHC).7 Thus, we had not been made aware of the clinical course, treatment, or prognosis for CA24-associated endotheliitis. Here, we report a case of corneal endothelial dysfunction due to CA24associated corneal endotheliitis that developed after cataract surgery.
CASE REPORT A 55-year-old man was admitted for cataract surgery during the season of AHC. At admission, his best-corrected visual acuity (BCVA) was 20/40 in the right eye and 20/50 in the left eye. The intraocular pressure (IOP) was 14 mm Hg in both eyes. The preoperative slit-lamp examination was normal except for the cataracts, and the specular microscopic finding showed normal endothelial cell density in both eyes: 2850 cells per square millimeter (right eye) and 2932 cells per square millimeter (left eye). Because he had no symptoms of conjunctivitis, such as conjunctival injection, itching sensation, or conjunctival discharge, phacoemulsification and posterior chamber intraocular lens implantation using 3.0-mm sized clear corneal incision was performed first in the right eye and then 3 days later in the left eye. No suture was placed after the surgery. The surgery was uneventful with no intraoperative complications. One day after cataract surgery in his left eye, the uncorrected visual acuity (UCVA) was 20/20 (right eye) and 20/25 (left eye), and the slit-lamp examination revealed slightly injected conjunctiva with mild anterior chamber reaction in both eyes, which were acceptable as immediate postoperative findings. The patient was discharged with routine postoperative topical antibiotics and steroids. Four days after cataract surgery in his left eye, the patient came to our clinic with complaints of ocular pain and decreased vision in the left eye. The UCVA of his left eye was decreased to 20/125, and the slit-lamp examination showed diffuse corneal stromal edema with Descemet folds and mild anterior chamber reaction (Fig. 1A). Considering the possibility of endophthalmitis, atypical toxic anterior segment syndrome (TASS), or corneal endotheliitis of viral origin, moxifloxacin 0.5% (Vigamox; Alcon, Fort Worth, TX) was started 6 times a day with prednisolone acetate 1% (Pred Forte; Allergan, Irvine, CA) every 1 hour, sodium chloride 5% (Muro 128; Bausch & Lomb, Tampa, FL) every 2 hours, 30 mg oral prednisolone per day (Nisolone Tab; Kukje Pharm, Seongnam, Korea), and 500 mg oral famciclovir (Famciclovir; Smithkline Beecham, Welwyn, UK) 2 times per day. He was observed daily; however, there was no sign of clinical improvement. www.corneajrnl.com |
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Lim et al
Cornea Volume 33, Number 5, May 2014
FIGURE 2. An electron microscope image reveals coxsackievirus A24 (CA24) viral antigens in a normal human fetal lung fibroblast (MRC-5) cell line through an indirect immunofluorescent technique (·200). The CA24 antigen is indicated by bright yellow fluorescence (red arrows) when examined under electron photomicroscopy (EPM).
DISCUSSION
FIGURE 1. A, An anterior segment photograph of the left eye taken on postoperative day 4 shows corneal stromal edema with Descemet folds. B, An anterior segment photograph of the left eye taken 6 months after surgery shows corneal stromal edema with Descemet folds. No improvement is seen compared with the photograph taken on postoperative day 4. Three days after the onset of symptoms (7 days after cataract surgery in his left eye), irrigation and aspiration of the anterior chamber were performed with virus culture and diagnostic polymerase chain reaction (PCR) of the aqueous humor for HSV-1, HSV-2, and VZV. Because other patients and their caregivers, including the patient’s caregivers, had been suffering from AHC when the patient was admitted for cataract surgery, viral culture, including adenoviruses, CA24, and enteroviruses was performed. PCR for HSV-1, HSV-2, and VZV were negative; however, viral particles were observed in viral culture. CA24 infection was confirmed by identification of viral antigens using electron photomicroscopic (EPM) examination of normal human fetal lung fibroblast (MRC-5) and human epidermoid carcinoma (Hep-2) cell lines through an indirect immunofluorescent technique using Light Diagnostics (EMD Millipore, Billerica, MA) (Fig. 2). The above-mentioned treatment regimen was continued for 1 month. However, neither the visual impairments nor the corneal edema showed improvement after 6 months (Fig. 1B). The BCVA was 20/200 in the left eye, and the endothelial cell count was not measured by specular microscopy because of severe corneal edema. Keratoplasty was recommended to restore vision, but the patient refused to receive the surgery.
534
| www.corneajrnl.com
This is the first case of CA24-associated endotheliitis confirmed by viral culture from an aqueous humor sample. CA24 belongs to the enterovirus genus and consists of an icosahedral capsid made up of 4 structural proteins (VP1, VP2, VP3, and VP4).8 The outbreak of AHC in Korea was caused by CA24, which, together with adenoviruses and enterovirus70, comprises the major group of etiological agents involved in AHC outbreaks worldwide.9 The patient did not present any preoperative or immediate postoperative symptoms of AHC after the cataract surgery, although it was an endemic period of AHC. Corneal endotheliitis developed 4 days after the surgery, and CA24 was detected in the aqueous humor by anterior chamber paracentesis. Isolation of the causative virus in cell culture gives a definitive diagnosis of viral infection. In the case of corneal endotheliitis, detection of virus from corneal endothelium is an ideal method for diagnosis; however, it is practically difficult to obtain corneal endothelial tissue if the patient is not undergoing keratoplasty. Several previous reports suggested that viral detection in the aqueous humor helps the diagnosis of corneal endotheliitis.3,5,10,11 These reports demonstrated the usefulness of an aqueous humor sample to confirm the virus causative of corneal endotheliitis. In virological investigations using aqueous humor, both viral culture and PCR can be performed. Conventionally, viral culture is considered the gold standard for detecting viral antigen; however, it requires a relatively long time to detect slow-growing viruses. Conversely, PCR is easy to perform, reasonably sensitive, and highly specific for the diagnosis of viral infection.3,5,12 Confocal microscopy is useful in some cases.13,14 For example, an intranuclear inclusion body seen on confocal microscopy is characteristic of CMV infection.13 In this case, anterior chamber paracentesis and viral culture from the aqueous humor with immunostaining were performed. Subsequent EPM examination through an indirect 2014 Lippincott Williams & Wilkins
Cornea Volume 33, Number 5, May 2014
immunofluorescent technique using a monoclonal antibody detected CA24. There have been previous reports of corneal endotheliitis diagnosed by viral culture from an aqueous humor sample. Robin et al10 detected HSV type 1 antigen in cells from the anterior chamber of a patient with corneal endotheliitis in 1985. Madhavan et al11 detected a kind of vesicular virus (family Rhabdoviridae) in the aqueous humor of a patient with corneal endotheliitis by electron microscopy. However, to the best of our knowledge, CA24 has never been reported as a causative virus of corneal endotheliitis by either viral culture or PCR from aqueous humor. At present, the source of the CA24 infection causing corneal endotheliitis is unclear. If the origin were from solutions or instruments contaminated during the cataract surgery, it is expected that widely spread AHC or CA24 endotheliitis in contemporary patients who underwent cataract surgery, would occur because of extremely high contagiousness of CA24. However, other patients who underwent surgeries with the same instruments in the same operating room on the same day presented no abnormal postoperative findings. Therefore, the possibility of CA24 infection during the surgical procedure seems to be very low. Then, the possibility of contamination by CA24 inoculated in the conjunctival or corneal surface without clinical manifestations should be considered. Endotheliitis is not developed by viral infection only but by immune-mediated response. Khodadoust et al2 proposed an autoimmune mechanism acting against the corneal endothelium to be the etiology of corneal endotheliitis in 1982. They reported 2 cases of bilateral corneal endotheliitis that had peripheral corneal edema and linear keratic precipitates, and the presence of inflammatory cells in the anterior chamber and a good response to topical corticosteroids supported their hypothesis about the autoimmune mechanism of corneal endotheliitis. According to Zheng et al,15 an in vivo study of rabbits infected intracamerally with HSV-1 showed that anterior chamber-associated immune deviation due to viral antigen played a pivotal role in corneal endotheliitis development, permitting the virus to invade and damage corneal endothelial cells. The experiment demonstrated that intrastromal inoculation of viral antigen followed by sameeye intracameral viral infection could promote stromal keratitis or keratouveitis, but not corneal endotheliitis. Otherwise, if the fellow eye was intracamerally infected with the virus after inoculation of viral antigen, antigen-specific delayed hypersensitivity was selectively suppressed and showed a specific pattern of inflammation that greatly resembled clinical features of corneal endotheliitis. Herein, we can hypothesize that CA24 viral antigens innoculated in the conjunctival or corneal surface, entered the anterior chamber during the first cataract surgery of the right eye. In AHC, symptoms start after an incubation period of 12–48 hours, and the clinical signs usually disappear in 1–2 weeks.16 The patient underwent cataract surgery first in the right eye and then 3 days later in the left eye, so it could be a latent period for AHC, although no suspicious symptoms or signs for AHC were present at the surgery time. Postoperative first day slit-lamp
2014 Lippincott Williams & Wilkins
A Case of Coxsackievirus A24 Corneal Endotheliitis
examination revealed mild conjunctival injection only without ocular pain, foreign body sensation, irritation, epiphora, photophobia, or subconjunctival hemorrhage, which would seem unlikely in AHC, then the second cataract surgery of the left eye was conducted. At that time, the left eye might have been intracamerally infected with the virus and corneal endotheliitis was occurred by a viral antigen-specific immune mechanism. In conclusion, this is the first case of viral cultureconfirmed CA24-associated corneal endotheliitis of the affected eye after cataract surgery. We suggest that caution might help in the decision to conduct cataract surgery during AHC season, even if the patient does not show any symptoms indicative of conjunctivitis. We would in the future advise avoiding elective ophthalmic surgery on an individual whose family members are afflicted with AHC. The mechanism of corneal endotheliitis caused by the CA24 will require further investigation.
REFERENCES 1. Sutcliffe E, Baum J. Acute idiopathic corneal endotheliitis. Ophthalmology. 1984;91:1161–1165. 2. Khodadoust AA, Attarzadeh A. Presumed autoimmune corneal endotheliopathy. Am J Ophthalmol. 1982;93:718–722. 3. Ohashi Y, Yamamoto S, Nishida K, et al. Demonstration of herpes simplex virus DNA in idiopathic corneal endotheliopathy. Am J Ophthalmol. 1991;112:419–423. 4. Maudgal PC, Missotten L, De Clercq E, et al. Varicella-zoster virus in the human corneal endothelium: a case report. Bull Soc Belge Ophtalmol. 1980;190:71–86. 5. Koizumi N, Yamasaki K, Kawasaki S, et al. Cytomegalovirus in aqueous humor from an eye with corneal endotheliitis. Am J Ophthalmol. 2006; 141:564–565. 6. Singh K, Sodhi PK. Mumps-induced corneal endotheliitis. Cornea 2004; 23:400–402. 7. Yin-Murphy M, Baharuddin-Ishak, Phoon MC, et al. A recent epidemic of Coxsackie virus type A24 acute haemorrhagic conjunctivitis in Singapore. Br J Ophthalmol. 1986;70:869–873. 8. Lévêque N, Amine IL, Cartet G, et al. Two outbreaks of acute hemorrhagic conjunctivitis in Africa due to genotype III coxsackievirus A24 variant. Eur J Clin Microbiol Infect Dis. 2007;26:199–202. 9. Chatterjee S, Quarcoopome CO, Apenteng A. Unusual type of epidemic conjunctivitis in Ghana. Br J Ophthalmol. 1970;54:628–630. 10. Robin JB, Steigner JB, Kaufman HE. Progressive herpetic corneal endotheliitis. Am J Ophthalmol. 1985;100:336–337. 11. Madhavan HN, Goldsmith CS, Rao SK, et al. Isolation of a vesicular virus belonging to the family rhabdoviridae from the aqueous humor of a patient with bilateral corneal endotheliitis. Cornea. 2002;21: 333–335. 12. Yamamoto S, Pavan-Langston D, Kinoshita S, et al. Detecting herpesvirus DNA in uveitis using the polymerase chain reaction. Br J Ophthalmol. 1996;80:465–468. 13. Shiraishi A, Hara Y, Takahashi M, et al. Demonstration of “owl’s eye” morphology by confocal microscopy in a patient with presumed cytomegalovirus corneal endotheliitis. Am J Ophthalmol. 2007;143:715–717. 14. Hillenaar T, Weenen C, Wubbels RJ, et al. Endothelial involvement in herpes simplex virus keratitis: an in vivo confocal microscopy study. Ophthalmology. 2009;116:2077–2086.e1–2. 15. Zheng X, Yamaguchi M, Goto T, et al. Experimental corneal endotheliitis in rabbit. Invest Ophthalmol Vis Sci. 2000;41:377–385. 16. Tavares FN, Costa EV, Oliveira SS, et al. Acute hemorrhagic conjunctivitis and coxsackievirus A24v, Rio de Janeiro, Brazil, 2004. Emerg Infect Dis. 2006;12:495–497.
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