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Adenovirus detected by polymerase chain reaction in multidose eyedrop bottles used by patients with adenoviral keratoconjunctivitis
Kikuchi M. Ocular manifestations of adult T-cell leukemia/ lymphoma. A clinicopathologic study. Ophthalmology 1993; 100:1794 –1799.
Adenovirus Detected by Polymerase Chain Reaction in Multidose Eyedrop Bottles Used by Patients With Adenoviral Keratoconjunctivitis Eiichi Uchio, MD, PhD, Hiroaki Ishiko, DVM, PhD, Koki Aoki, MD, PhD, and Shigeaki Ohno, MD, PhD
FIGURE 1. Time course of adenovirus detection rate in multidose eyedrop bottles.
PURPOSE:
We investigated the potential of a multidose eyedrop bottle used by patients with adenoviral keratoconjunctivitis as a source for spreading infection. DESIGN: Prospective consecutive case series. METHODS: The contents of multidose eyedrop bottles given to patients with adenoviral conjunctivitis and in use for 1 week were analyzed by polymerase chain reaction for adenovirus after as long as 9 weeks of preservation at room temperature. RESULTS: Of 26 patients with adenoviral keratoconjunctivitis, the eyedrop bottles of 19 patients (73%) were positive for adenovirus. The maximum detection interval was 9 weeks. Significantly higher prevalences of intrafamilial infection (P ⴝ .0098) and of corneal subepithelial opacity (P ⴝ .046) were observed among cases with adenoviral contamination than among cases without contamination. CONCLUSIONS: Multidose bottles used by patients with adenoviral keratoconjunctivitis are a possible vector for viral transmission for as long as 9 weeks. (Am J Ophthalmol 2002;134:618 – 619. © 2002 by Elsevier Science Inc. All rights reserved.)
I
maximum length of time it survived in multidose eyedrop bottles used by patients with adenoviral keratoconjunctivitis. We used polymerase chain reaction (PCR) to investigate the potential of a multidose bottle as a source for spreading infection. The cases consisted of 26 consecutive patients with a mean age of 34.1 years from whose conjunctival swabs adenovirus was detected by PCR analysis4 and three patients without signs of acute conjunctivitis. This study was carried out with approval from the appropriate institutional review board and informed consent was obtained from the patients. Sixty-five bottles of three kinds of commercially available eyedrops—azulene sulfonate sodium 0.02% (45 bottles), dexamethasone metasulfobenzonate sodium 0.1% (13 bottles), and ofloxacin 0.3% (7 bottles)—that had been given to the patients at their first visit and had been used for 1 week were collected for virologic examination and preserved at room temperature. From each container, a swab was used to obtain a sample from the inside of the cap, the rim of the bottle, and the dispensing tip. Additionally, a drop was squeezed onto a cotton swab. Polymerase chain reaction restriction fragment length polymorphism analysis was performed to determine the serotypes of adenovirus as previously described.4 Swabbing was repeated in 12 bottles once a week for as long as 9 weeks. Of 26 patients with adenoviral keratoconjunctivitis, the eyedrop bottles of 19 patients (73%) were positive for adenovirus type 8 (Ad8, 10 cases), Ad3 (3), Ad4 (2), Ad 7 (2) and Ad37 (2). Serotypes detected from conjunctival swabs and eyedrop bottles were identical in all cases. No patient without signs of acute conjunctivitis showed a positive result for adenovirus. The maximum detection interval for multidose eyedrop bottles preserved at room temperature was 9 weeks in 4 bottles (40%; Figure 1). No significant difference was observed in the positive rate of adenovirus serotypes between the sites of sample collection (Table 1). A significantly higher prevalence of intrafamil-
T HAS BEEN DEMONSTRATED THAT ADENOVIRUS CAN
survive for 35 days on plastic surfaces,1 49 days on metal surfaces,2 and 10 days on cloth.1 Adenovirus has been recovered from multidose bottles of topical fluorescein for as long as 21 days in an experimental situation.3 In this study, we determined the presence of adenovirus and the Accepted for publication May 7, 2002. From the Department of Ophthalmology (E.U.), Yokohama City University Medical Center, Yokohama, Japan; Mitsubishi Kagaku Bioclinical Laboratories, Inc. (H. I.), Tokyo, Japan; and the Department of Ophthalmology (K.A., S.O.), Hokkaido University Graduate School of Medicine, Sapporo, Japan. Supported by a Grant-in-Aid for Encouragement of Scientists (11671752) from the Ministry of Education, Science, Sports and Culture of Japan. Inquiries to Eiichi Uchio, MD, Department of Ophthalmology, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama 232-0024, Japan; fax: (⫹81)45-253-8490; e-mail: euchio@ urahp.yokohama-cu.ac.jp
618
AMERICAN JOURNAL
OF
OPHTHALMOLOGY
OCTOBER 2002
TABLE 1. Detection of Different Serotypes of Adenovirus From Conjunctiva and Eyedrop Bottles by the Polymerase Chain Reaction Method
5. Azar MJ, Dhaliwal DK, Bower KS, Kowalski RP, Gordon YJ. Possible consequence of shaking hands with your patients with epidemic keratoconjunctivitis. Am J Ophthalmol 1996;121: 711–712.
Site of Specimen Collection
Serotype
Conjunctiva (Cases)
Eyedrop Bottles (Cases)
Ad 3 Ad 4 Ad 7 Ad 8 Ad 11 Ad 37 Total
3 2 1 15 1 2 24
2 2 1 10 0 2 17
Anna J. Park, MD, Guy F. Webster, MD, PhD, Robert B. Penne, MD, and Irving M. Raber, MD PURPOSE:
Ad ⫽ adenovirus.
ial infection of adenoviral conjunctivitis diagnosed by PCR analysis, 58% (11/19), was observed among cases with adenoviral contamination than among cases without contamination, 0% (0/7; P ⫽ .0098). Two cases had used eyedrops given to other family members from whom adenovirus was detected. The prevalence of corneal subepithelial opacity in cases using contaminated multidose bottles, 74% (14/19), was significantly higher than that in cases without contamination, 29% (2/7; P ⫽ .046). Our results indicate that multidose bottles used by patients are a possible vector for adenoviral transmission to at-risk persons, especially the family members of patients with adenoviral keratoconjunctivitis. Although there are many modes of transmission of adenovirus other than eyedrop bottles in domestic situations, such as hands,5 towels, and furniture, it is important that patients with adenoviral keratoconjunctivitis should be alerted to the risk of contamination with multidose bottles. The significantly higher prevalence of subepithelial corneal opacity among adenovirus-contaminated cases than among cases without contamination may have been due to the repeated challenge of adenovirus from eyedrops; however, the exact reason remains unclear. REFERENCES
1. Nauheim RC, Romanowski EG, Cruz TA, et al. Prolonged recoverability of desiccated adenovirus type 19 from various surfaces. Ophthalmology 1990;97:1450 –1453. 2. Gordon YJ, Gordon RY, Romanowski EG, Arullo-Cruz TP. Prolonged recovery of desiccated adenoviral serotypes 5, 8, and 19 from plastic and metal surfaces in vitro. Ophthalmology 1993;100:1835–1840. 3. Kowalski RP, Romanowski EG, Waikhom B, Gordon YJ. The survival of adenovirus in multidose bottles of topical fluorescein. Am J Ophthalmol 1998;126:835– 836. 4. Saitoh W, Itoh N, Uchio E, et al. Rapid diagnosis of adenoviral conjunctivitis with polymerase chain reaction and restriction fragment polymorphism analysis. J Clin Microbiol 1996;34:2113–2116.
VOL. 134, NO. 4
Porphyria Cutanea Tarda Presenting as Cicatricial Conjunctivitis
To report a case of porphyria cutanea tarda presenting as cicatricial conjunctivitis. DESIGN: Observational study. METHODS: A 31-year-old man presented with bilateral inferior symblepharon, superior tarsal conjunctival scarring and concretions, and recurrent conjunctival and episcleral injection. RESULTS: Four years after initial presentation, the patient developed hepatitis C, and 2 years later blisters on his scalp and hands. Direct immunofluorescence studies of biopsies taken from the palpebral conjunctiva of the right lower lid were negative for cicatricial pemphigoid. A twenty-four hour urine specimen analysis revealed elevated levels of uroporphyrins and polycarboxylated porphyrins, confirming the diagnosis of porphyria cutanea tarda. The patient was treated with repeated phlebotomies and oral hydroxychloroquine, which resulted in a significant decrease in the skin lesions, conjunctival injection, and concretions under the upper lids. CONCLUSIONS: Cicatricial conjunctivitis may be a manifestation of porphyria cutanea tarda. (Am J Ophthalmol 2002;134:619 – 621. © 2002 by Elsevier Science Inc. All rights reserved.)
T
HE PORPHYRIAS ARE A GROUP OF INHERITED OR AC-
quired disorders of specific enzymes involved in heme biosynthesis. Seven different porphyrias have been described, each with a unique pattern of excessive accumulation and excretion of porphyrins. Porphyria cutanea tarda is the most common form of porphyria.1 It occurs in either an autosomal dominant or a sporadic pattern and the biochemical defect is a deficiency of uroporphyrinogen decarboxylase in the liver. The onset of the disease is usually in the third to fourth decades. Precipitating factors include alcohol, hepatitis C, and estrogens (in oral contraceptives and hormone replacement therapy). Cutaneous manifestations of the disease include skin fragility, vesicles and bullae on sun-exposed surfaces, and hyperpigmentaAccepted for publication May 10, 2002. From the Cornea Service (A.J.P., I.M.R.), the Department of Dermatology (G.F.W.), and the Plastics Service (R.B.P.), Wills Eye Hospital, Jefferson Medical College, Philadelphia, Pennsylvania. Inquiries to Anna J. Park, MD, Cornea Service, Wills Eye Hospital, 900 Walnut St, Philadelphia, PA 19107; fax: (215) 928-3854; e-mail: [email protected]
BRIEF REPORTS
619
Adenovirus Detected by Polymerase Chain Reaction in Multidose Eyedrop Bottles Used by Patients With Adenoviral Keratoconjunctivitis Eiichi Uchio, MD, PhD, Hiroaki Ishiko, DVM, PhD, Koki Aoki, MD, PhD, and Shigeaki Ohno, MD, PhD
FIGURE 1. Time course of adenovirus detection rate in multidose eyedrop bottles.
PURPOSE:
We investigated the potential of a multidose eyedrop bottle used by patients with adenoviral keratoconjunctivitis as a source for spreading infection. DESIGN: Prospective consecutive case series. METHODS: The contents of multidose eyedrop bottles given to patients with adenoviral conjunctivitis and in use for 1 week were analyzed by polymerase chain reaction for adenovirus after as long as 9 weeks of preservation at room temperature. RESULTS: Of 26 patients with adenoviral keratoconjunctivitis, the eyedrop bottles of 19 patients (73%) were positive for adenovirus. The maximum detection interval was 9 weeks. Significantly higher prevalences of intrafamilial infection (P ⴝ .0098) and of corneal subepithelial opacity (P ⴝ .046) were observed among cases with adenoviral contamination than among cases without contamination. CONCLUSIONS: Multidose bottles used by patients with adenoviral keratoconjunctivitis are a possible vector for viral transmission for as long as 9 weeks. (Am J Ophthalmol 2002;134:618 – 619. © 2002 by Elsevier Science Inc. All rights reserved.)
I
maximum length of time it survived in multidose eyedrop bottles used by patients with adenoviral keratoconjunctivitis. We used polymerase chain reaction (PCR) to investigate the potential of a multidose bottle as a source for spreading infection. The cases consisted of 26 consecutive patients with a mean age of 34.1 years from whose conjunctival swabs adenovirus was detected by PCR analysis4 and three patients without signs of acute conjunctivitis. This study was carried out with approval from the appropriate institutional review board and informed consent was obtained from the patients. Sixty-five bottles of three kinds of commercially available eyedrops—azulene sulfonate sodium 0.02% (45 bottles), dexamethasone metasulfobenzonate sodium 0.1% (13 bottles), and ofloxacin 0.3% (7 bottles)—that had been given to the patients at their first visit and had been used for 1 week were collected for virologic examination and preserved at room temperature. From each container, a swab was used to obtain a sample from the inside of the cap, the rim of the bottle, and the dispensing tip. Additionally, a drop was squeezed onto a cotton swab. Polymerase chain reaction restriction fragment length polymorphism analysis was performed to determine the serotypes of adenovirus as previously described.4 Swabbing was repeated in 12 bottles once a week for as long as 9 weeks. Of 26 patients with adenoviral keratoconjunctivitis, the eyedrop bottles of 19 patients (73%) were positive for adenovirus type 8 (Ad8, 10 cases), Ad3 (3), Ad4 (2), Ad 7 (2) and Ad37 (2). Serotypes detected from conjunctival swabs and eyedrop bottles were identical in all cases. No patient without signs of acute conjunctivitis showed a positive result for adenovirus. The maximum detection interval for multidose eyedrop bottles preserved at room temperature was 9 weeks in 4 bottles (40%; Figure 1). No significant difference was observed in the positive rate of adenovirus serotypes between the sites of sample collection (Table 1). A significantly higher prevalence of intrafamil-
T HAS BEEN DEMONSTRATED THAT ADENOVIRUS CAN
survive for 35 days on plastic surfaces,1 49 days on metal surfaces,2 and 10 days on cloth.1 Adenovirus has been recovered from multidose bottles of topical fluorescein for as long as 21 days in an experimental situation.3 In this study, we determined the presence of adenovirus and the Accepted for publication May 7, 2002. From the Department of Ophthalmology (E.U.), Yokohama City University Medical Center, Yokohama, Japan; Mitsubishi Kagaku Bioclinical Laboratories, Inc. (H. I.), Tokyo, Japan; and the Department of Ophthalmology (K.A., S.O.), Hokkaido University Graduate School of Medicine, Sapporo, Japan. Supported by a Grant-in-Aid for Encouragement of Scientists (11671752) from the Ministry of Education, Science, Sports and Culture of Japan. Inquiries to Eiichi Uchio, MD, Department of Ophthalmology, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama 232-0024, Japan; fax: (⫹81)45-253-8490; e-mail: euchio@ urahp.yokohama-cu.ac.jp
618
AMERICAN JOURNAL
OF
OPHTHALMOLOGY
OCTOBER 2002
TABLE 1. Detection of Different Serotypes of Adenovirus From Conjunctiva and Eyedrop Bottles by the Polymerase Chain Reaction Method
5. Azar MJ, Dhaliwal DK, Bower KS, Kowalski RP, Gordon YJ. Possible consequence of shaking hands with your patients with epidemic keratoconjunctivitis. Am J Ophthalmol 1996;121: 711–712.
Site of Specimen Collection
Serotype
Conjunctiva (Cases)
Eyedrop Bottles (Cases)
Ad 3 Ad 4 Ad 7 Ad 8 Ad 11 Ad 37 Total
3 2 1 15 1 2 24
2 2 1 10 0 2 17
Anna J. Park, MD, Guy F. Webster, MD, PhD, Robert B. Penne, MD, and Irving M. Raber, MD PURPOSE:
Ad ⫽ adenovirus.
ial infection of adenoviral conjunctivitis diagnosed by PCR analysis, 58% (11/19), was observed among cases with adenoviral contamination than among cases without contamination, 0% (0/7; P ⫽ .0098). Two cases had used eyedrops given to other family members from whom adenovirus was detected. The prevalence of corneal subepithelial opacity in cases using contaminated multidose bottles, 74% (14/19), was significantly higher than that in cases without contamination, 29% (2/7; P ⫽ .046). Our results indicate that multidose bottles used by patients are a possible vector for adenoviral transmission to at-risk persons, especially the family members of patients with adenoviral keratoconjunctivitis. Although there are many modes of transmission of adenovirus other than eyedrop bottles in domestic situations, such as hands,5 towels, and furniture, it is important that patients with adenoviral keratoconjunctivitis should be alerted to the risk of contamination with multidose bottles. The significantly higher prevalence of subepithelial corneal opacity among adenovirus-contaminated cases than among cases without contamination may have been due to the repeated challenge of adenovirus from eyedrops; however, the exact reason remains unclear. REFERENCES
1. Nauheim RC, Romanowski EG, Cruz TA, et al. Prolonged recoverability of desiccated adenovirus type 19 from various surfaces. Ophthalmology 1990;97:1450 –1453. 2. Gordon YJ, Gordon RY, Romanowski EG, Arullo-Cruz TP. Prolonged recovery of desiccated adenoviral serotypes 5, 8, and 19 from plastic and metal surfaces in vitro. Ophthalmology 1993;100:1835–1840. 3. Kowalski RP, Romanowski EG, Waikhom B, Gordon YJ. The survival of adenovirus in multidose bottles of topical fluorescein. Am J Ophthalmol 1998;126:835– 836. 4. Saitoh W, Itoh N, Uchio E, et al. Rapid diagnosis of adenoviral conjunctivitis with polymerase chain reaction and restriction fragment polymorphism analysis. J Clin Microbiol 1996;34:2113–2116.
VOL. 134, NO. 4
Porphyria Cutanea Tarda Presenting as Cicatricial Conjunctivitis
To report a case of porphyria cutanea tarda presenting as cicatricial conjunctivitis. DESIGN: Observational study. METHODS: A 31-year-old man presented with bilateral inferior symblepharon, superior tarsal conjunctival scarring and concretions, and recurrent conjunctival and episcleral injection. RESULTS: Four years after initial presentation, the patient developed hepatitis C, and 2 years later blisters on his scalp and hands. Direct immunofluorescence studies of biopsies taken from the palpebral conjunctiva of the right lower lid were negative for cicatricial pemphigoid. A twenty-four hour urine specimen analysis revealed elevated levels of uroporphyrins and polycarboxylated porphyrins, confirming the diagnosis of porphyria cutanea tarda. The patient was treated with repeated phlebotomies and oral hydroxychloroquine, which resulted in a significant decrease in the skin lesions, conjunctival injection, and concretions under the upper lids. CONCLUSIONS: Cicatricial conjunctivitis may be a manifestation of porphyria cutanea tarda. (Am J Ophthalmol 2002;134:619 – 621. © 2002 by Elsevier Science Inc. All rights reserved.)
T
HE PORPHYRIAS ARE A GROUP OF INHERITED OR AC-
quired disorders of specific enzymes involved in heme biosynthesis. Seven different porphyrias have been described, each with a unique pattern of excessive accumulation and excretion of porphyrins. Porphyria cutanea tarda is the most common form of porphyria.1 It occurs in either an autosomal dominant or a sporadic pattern and the biochemical defect is a deficiency of uroporphyrinogen decarboxylase in the liver. The onset of the disease is usually in the third to fourth decades. Precipitating factors include alcohol, hepatitis C, and estrogens (in oral contraceptives and hormone replacement therapy). Cutaneous manifestations of the disease include skin fragility, vesicles and bullae on sun-exposed surfaces, and hyperpigmentaAccepted for publication May 10, 2002. From the Cornea Service (A.J.P., I.M.R.), the Department of Dermatology (G.F.W.), and the Plastics Service (R.B.P.), Wills Eye Hospital, Jefferson Medical College, Philadelphia, Pennsylvania. Inquiries to Anna J. Park, MD, Cornea Service, Wills Eye Hospital, 900 Walnut St, Philadelphia, PA 19107; fax: (215) 928-3854; e-mail: [email protected]
BRIEF REPORTS
619