- Email: [email protected]
Short-term Intraocular Pressure Trends After Intravitreal Triamcinolone Injection
5. Oshitari T, Roy S. Diabetes: a potential enhancer of retinal injury in rat retinas. Neurosci Lett 2005;390:25–30. 6. Bonovas S, Peponis V, Filiousso K. Diabetes mellitus as a risk factor for primary open-angle glaucoma: a meta-analysis. Diabet Med 2004;21:609 – 614.
Short-term Intraocular Pressure Trends After Intravitreal Triamcinolone Injection Edward W. Lee, MD, Seenu M. Hariprasad, MD, William F. Mieler, MD, Tricia L. Newman, OD, and Rajendra S. Apte, MD, PhD FIGURE. Coefficient of correlation between HbA1c and intraocular pressure (IOP) in patients with diabetes with chronic hyperglycemia. To examine dose-response effect of chronic hyperglycemia on IOP, we calculated correlation between glycosylated hemoglobin A1c (HbA1c) and IOP in all patients who satisfied study criteria (n ⴝ 190). Linear regression line was fitted with data (r ⴝ .146; P ⴝ .044 by Pearson correlation coefficient).
addition, rats with diabetes have been reported to develop retinal injury and have a higher rate of retinal ganglion cell death.5 Long-term follow-up of the cohort to establish whether these patients with higher IOP and higher HbA1c levels are more likely to develop open-angle glaucoma is needed to demonstrate the clinical importance of our findings. In conclusion, our results showed that chronic hyperglycemia was associated with higher IOP in patients with diabetes, and we assumed that the increase of IOP was related to accumulation of fibronectin in trabecular meshwork tissue. THE AUTHORS INDICATE NO FINANCIAL SUPPORT OR FInancial conflict of interest. Involved in design of study (T.O., N.F., K.H., E.A.-U.); involved in collection, management, analysis and interpretation of data, and preparation of the data (T.O., N.F., K.H., E.A.-U.); and involved in management, statistical analysis, review and interpretation of the data, and preparation of the manuscript (T.O., N.F., K.H., E.A.-U.). REFERENCES
1. Sato T, Roy S. Effect of high glucose on fibronectin expression and cell proliferation in trabecular meshwork cells. Invest Ophthalmol Vis Sci 2002;43:170 –175. 2. Li AF, Tane N, Roy S. Fibronectin overexpression inhibits trabecular meshwork cell monolayer permeability. Mol Vis 2004;10:750 –757. 3. Dielemans I, de Jong PTVM, Stolk R, et al. Primary openangle glaucoma, intraocular pressure, and diabetes mellitus in the general elderly population: the Rotterdam Study. Ophthalmology 1996;103:1271–1275. 4. Iwase A, Suzuki Y, Araie M, et al. The prevalence of primary open-angle glaucoma in Japanese: the Tajimi Study. Ophthalmology 2004;111:1641–1648.
VOL. 143, NO. 2
To report the trends in intraocular pressures (IOP) within the first week after intravitreal injection of triamcinolone acetonide (Kenalog) for the treatment of retinal disease. DESIGN: Retrospective chart review. METHODS: Review of 43 consecutive patients and 50 intravitreal injections of 4 mg triamcinolone acetonide. Analysis of the effect on IOP was performed. RESULTS: The mean preinjection IOP was 14.60 ⴞ 3.71 mm Hg (mean ⴞ SD) (range, 9 to 26 mm Hg). The mean postinjection IOP (30 minutes after injection) was 19.64 ⴞ 7.43 mm Hg (range, 5 to 45 mm Hg). Mean IOP change before and after injection was 4.83 ⴞ 7.10 mm Hg. The mean IOP one to two days after injection was 15.32 ⴞ 4.41. mm Hg (range, 6 to 27 mm Hg). The mean IOP five to seven days after injection was 15.94 ⴞ 4.86 mm Hg (range, 5 to 28 mm Hg). CONCLUSIONS: Intravitreal triamcinolone acetonide injection in this limited series does not cause a marked increase in IOP within the first week after the procedure. (Am J Ophthalmol 2007;143:365–367. © 2007 by Elsevier Inc. All rights reserved.) PURPOSE:
T
HE USE OF INTRAVITREAL TRIAMCINOLONE ACE-
tonide (Kenalog, Bristol-Myers Squibb, New York, New York, USA) is a common treatment for a variety of vitreoretinal diseases. Although it has been shown that triamcinolone acetonide can cause a delayed increase in intraocular pressure (IOP), the change in IOP within one week after injection has not been investigated. We report the effect of 4 mg intravitreal triamcinolone acetonide on IOP in the first week after injection. Approval from the Institutional Review Board of the University of Chicago was obtained before initiating this Accepted for publication Aug 22, 2006. From the University of Chicago School of Medicine, Department of Ophthalmology and Visual Science, Chicago, Illinois (E.W.L., S.M.H., W.F.M.); Illinois Eye Institute, Chicago, Illinois (T.L.N.); and Washington University in St Louis School of Medicine, Department of Ophthalmology and Visual Science, Barnes Retina Institute, St Louis, Missouri (R.S.A.). Inquiries to Seenu M. Hariprasad, MD, Department of Ophthalmology and Visual Science, University of Chicago, 5841 South Maryland, MC 2114, Chicago, IL 60637; e-mail: [email protected]
BRIEF REPORTS
365
FIGURE. Short-term intraocular pressure (IOP) changes after intravitreal triamcinolone injection. Graph illustrates preinjection IOP and postinjection IOP at 30 minutes, one to two days, and five to seven days after injection.
study. We performed a retrospective chart review of 43 patients who underwent 50 consecutive intravitreal injections of 4 mg (0.1 ml of 40 mg/ml) triamcinolone acetonide at the University of Chicago Retina Clinic. Preinjection IOP (within one hour of the injection) and postinjection IOP (at 30 minutes, one to two days, and five to seven days) were recorded. All IOPs were obtained by Goldmann applanation tonometry. Mean preinjection IOP was 14.60 ⫾ 3.71 mm Hg (mean ⫾ SD) (range, 9 to 26 mm Hg). Mean postinjection IOP (approximately 30 minutes after injection) was 19.64 ⫾ 7.43 mm Hg (range, 5 to 45 mm Hg). Mean IOP change before and after injection was 4.83 ⫾ 7.10 mm Hg. The mean IOP one to two days after injection was 15.32 ⫾ 4.41 mm Hg (range, 6 to 27 mm Hg). The mean IOP at five to seven days after injection was 15.94 ⫾ 4.86 mm Hg (range, 5 to 28 mm Hg) (Figure). None of the patients was treated with topical IOPlowering medications after injection. Paracentesis to lower IOP was not required in any patient. Two patients had pressures ⬎30 mm Hg within 30 minutes after injection. Over the course of an hour, the IOP normalized in these two patients to the mid-20s without pharmacologic intervention. In one patient, digital massage was implemented. At one week, the IOP was ⬍20 mm Hg in both of these patients. Although it is well established that intravitreal triamcinolone acetonide can cause a marked increase in IOP several weeks after injection as a result of so-called steroid response, the short-term IOP trends within the first week have not been clearly identified.1–5 The results of our study suggest that intravitreal triamcinolone acetonide does not 366
AMERICAN JOURNAL
cause a sustained increase in IOP within the first week after injection. A transient increase in IOP ⬎30 mm Hg was seen in two patients; however, this normalized within one hour without pharmacologic or surgical intervention. Benz and associates6 recently reported that IOP changes within the initial 30 minutes after intravitreal triamcinolone acetonide injection correlate with the presence of vitreous reflux. In their study, patients who were noted to have no vitreous reflux after injection had a marked increase in mean IOP, which normalized within 30 minutes. Patients who were noted to have vitreous reflux did not have an increase in mean IOP within 30 minutes of the injection. Our findings are consistent with theirs. Our study further demonstrates that the mean IOP does not greatly change from baseline within one week after injection. Singh and associates7 described a case series of three patients who experienced an early rapid increase in IOP approximately four to seven days after intravitreal triamcinolone acetonide injection. It was speculated this was due to migration of triamcinolone acetonide particles into the trabecular meshwork. These cases required filtration surgery to achieve pressure control. Notably, all these patients were pseudophakic. Our study did not have any patients with a sustained increased of IOP at one week. However, it may be prudent to check patients’ IOP within the first week after injection to avoid possible, albeit rare, uncontrolled glaucoma in pseudophakes. On the basis of our results, pharmacologic or surgical intervention is not necessary for an increase in IOP within the first day after intravitreal triamcinolone acetonide injection. We advise against paracentesis for IOP increased within OF
OPHTHALMOLOGY
FEBRUARY 2007
this time frame because this procedure is associated with complications such as lens damage, patient discomfort, and theoretical risk of increased infection. Additionally, it may not be necessary for the patient to remain at the clinic immediately after intravitreal injection for an IOP check. THIS STUDY WAS SUPPORTED BY AN UNRESTRICTED GRANT from the Research to Prevent Blindness, Inc, New York, New York. The authors indicate no financial conflict of interest. Involved in design of study (E.L., S.H., W.M., R.A.) collection, management, analysis and interpretation of data, and preparation of the data (E.L., S.H., W.M., R.A.); involved in collection of data (E.L., S.H., T.N.); and involved in the review, approval, and preparation of the manuscript (E.L., S.H., T.N., W.M., R.A.). REFERENCES
1. Jonas JB, Degenring RF, Kreissig I, Akkoyun I, Kamppeter BA. Intraocular pressure elevation after intravitreal triamcinolone acetonide injection. Ophthalmology 2005;112:593–598. 2. Smithen LM, Ober MD, Maranan L, Spaide RF. Intravitreal triamcinolone acetonide and intraocular pressure. Am J Ophthalmol 2004;138:740 –743. 3. Wingate RJ, Beaumont PE. Intravitreal triamcinolone and elevated intraocular pressure. Aust N Z J Ophthalmol 1999; 27:431– 432. 4. Jonas JB, Kreissig I, Degenring R. Intraocular pressure after intravitreal injection of triamcinolone acetonide. Br J Ophthalmol 2003;87:24 –27. 5. Kreissig I, Degenring RF, Jonas JB. Intraocular pressure after intravitreal triamcinolone acetonide. Ophthalmologe 2005; 102:153–157. 6. Benz MS, Albini TA, Holz ER, et al. Short-term course of intraocular pressure after intravitreal injection of triamcinolone acetonide. Ophthalmology 2006;113:1174 –1178. 7. Singh IP, Ahmad SI, Yeh D, et al. Early rapid rise in intraocular pressure after intravitreal triamcinolone acetonide injection. Am J Ophthalmol 2004;138:286 –287.
Strong Association Between HLA-A*0206 and Stevens-Johnson Syndrome in the Japanese Mayumi Ueta, MD, PhD, Chie Sotozono, MD, PhD, Katsushi Tokunaga, PhD, Toshio Yabe, PhD, and Shigeru Kinoshita, MD, PhD To investigate the association between HLA class I antigens and Stevens-Johnson syndrome (SJS)/
PURPOSE:
Accepted for publication Sept 12, 2006. From the Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kawaramachi, Kamigyo-ku, Kyoto, Japan (M.U., C.S., S.K.); the Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan (K.T.); and the Tokyo Metropolitan Red Cross Blood Center, Tatumi, Koutou-ku, Tokyo, Japan (T.Y.). Inquiries to Mayumi Ueta, MD, PhD, Department of Ophthalmology, Kyoto Prefectural University of Medicine, 465 Kajiicho, Hirokoji, Kawaramachi, Kamigyoku, Kyoto 602-0841, Japan; e-mail: mueta@ophth. kpu-m.ac.jp
VOL. 143, NO. 2
toxic epidermal necrolysis (TEN) with ocular complications in Japanese. DESIGN: Case-control study. METHODS: We examined the histocompatibility antigen genes HLA-A, -B, and -C of 40 Japanese SJS/TEN patients with ocular complications and 113 healthy Japanese volunteers by polymerase chain reaction amplification and subsequent hybridization with sequencespecific oligonucleotide probes (PCR-SSO). RESULTS: We clarified that HLA-A*0206 is strongly associated with SJS/TEN with ocular complications in the Japanese. CONCLUSIONS: Because this finding is completely different from data reported elsewhere on Taiwanese Han Chinese patients and Caucasian patients, it suggests strong ethnic differences in the HLA-SJS association and points to the need for studies in other ethnic populations in order to obtain a global picture. (Am J Ophthalmol 2007;143: 367–368. © 2007 by Elsevier Inc. All rights reserved.)
S
TEVENS-JOHNSON SYNDROME (SJS) AND TOXIC EPIDER-
mal necrolysis (TEN) are acute-onset mucocutaneous diseases induced by infectious agents and/or inciting drugs. Based on a large international case-control study, SJS and TEN are considered as severity variants of a single entity1; developing acute exanthema that progresses to limited (SJS) or more widespread (TEN) blistering and erosion of the skin and mucous membranes. Although rare, these reactions carry high morbidity and mortality rates. Ophthalmologists recognize the serious ocular complications leading to severe, lifelong visual dysfunction. Conjunctival invasion into the cornea attributable to corneal epithelial stem cell deficiency progresses despite healing of the skin lesions, and corneal opacity, neovascularization, symblepharon, ankyloblepharon, and in some instances, keratinization, appears on the ocular surface at the chronic stage. Interestingly, we observed that more than 95% of three patients out of 61 SJS/TEN with ocular complications had lost their fingernails in the acute stage and transformed nails often continue even after healing of the skin lesions. The reported incidence of ocular complications is 50% to 69%. The pathobiological mechanisms underlying the onset of SJS/TEN have not been fully established, although the involvement of immune mechanisms and an altered drug metabolism have been suggested. Whatever the pathogenetic events, the extreme rarity of cutaneous and ocular surface reactions to drug therapies led us to suspect individual susceptibility. We studied the histocompatibility antigen genes HLA-A, -B, and -C of Japanese SJS/TEN patients with ocular complications. The study was approved by the institutional review board, and consent was obtained from all participants in written form. The diagnosis of SJS/TEN was based on a confirmed history of the acute onset of high fever, serious mucocutaneous illness with skin eruptions, and involvement of at least two mucosal sites including the
BRIEF REPORTS
367
Short-term Intraocular Pressure Trends After Intravitreal Triamcinolone Injection Edward W. Lee, MD, Seenu M. Hariprasad, MD, William F. Mieler, MD, Tricia L. Newman, OD, and Rajendra S. Apte, MD, PhD FIGURE. Coefficient of correlation between HbA1c and intraocular pressure (IOP) in patients with diabetes with chronic hyperglycemia. To examine dose-response effect of chronic hyperglycemia on IOP, we calculated correlation between glycosylated hemoglobin A1c (HbA1c) and IOP in all patients who satisfied study criteria (n ⴝ 190). Linear regression line was fitted with data (r ⴝ .146; P ⴝ .044 by Pearson correlation coefficient).
addition, rats with diabetes have been reported to develop retinal injury and have a higher rate of retinal ganglion cell death.5 Long-term follow-up of the cohort to establish whether these patients with higher IOP and higher HbA1c levels are more likely to develop open-angle glaucoma is needed to demonstrate the clinical importance of our findings. In conclusion, our results showed that chronic hyperglycemia was associated with higher IOP in patients with diabetes, and we assumed that the increase of IOP was related to accumulation of fibronectin in trabecular meshwork tissue. THE AUTHORS INDICATE NO FINANCIAL SUPPORT OR FInancial conflict of interest. Involved in design of study (T.O., N.F., K.H., E.A.-U.); involved in collection, management, analysis and interpretation of data, and preparation of the data (T.O., N.F., K.H., E.A.-U.); and involved in management, statistical analysis, review and interpretation of the data, and preparation of the manuscript (T.O., N.F., K.H., E.A.-U.). REFERENCES
1. Sato T, Roy S. Effect of high glucose on fibronectin expression and cell proliferation in trabecular meshwork cells. Invest Ophthalmol Vis Sci 2002;43:170 –175. 2. Li AF, Tane N, Roy S. Fibronectin overexpression inhibits trabecular meshwork cell monolayer permeability. Mol Vis 2004;10:750 –757. 3. Dielemans I, de Jong PTVM, Stolk R, et al. Primary openangle glaucoma, intraocular pressure, and diabetes mellitus in the general elderly population: the Rotterdam Study. Ophthalmology 1996;103:1271–1275. 4. Iwase A, Suzuki Y, Araie M, et al. The prevalence of primary open-angle glaucoma in Japanese: the Tajimi Study. Ophthalmology 2004;111:1641–1648.
VOL. 143, NO. 2
To report the trends in intraocular pressures (IOP) within the first week after intravitreal injection of triamcinolone acetonide (Kenalog) for the treatment of retinal disease. DESIGN: Retrospective chart review. METHODS: Review of 43 consecutive patients and 50 intravitreal injections of 4 mg triamcinolone acetonide. Analysis of the effect on IOP was performed. RESULTS: The mean preinjection IOP was 14.60 ⴞ 3.71 mm Hg (mean ⴞ SD) (range, 9 to 26 mm Hg). The mean postinjection IOP (30 minutes after injection) was 19.64 ⴞ 7.43 mm Hg (range, 5 to 45 mm Hg). Mean IOP change before and after injection was 4.83 ⴞ 7.10 mm Hg. The mean IOP one to two days after injection was 15.32 ⴞ 4.41. mm Hg (range, 6 to 27 mm Hg). The mean IOP five to seven days after injection was 15.94 ⴞ 4.86 mm Hg (range, 5 to 28 mm Hg). CONCLUSIONS: Intravitreal triamcinolone acetonide injection in this limited series does not cause a marked increase in IOP within the first week after the procedure. (Am J Ophthalmol 2007;143:365–367. © 2007 by Elsevier Inc. All rights reserved.) PURPOSE:
T
HE USE OF INTRAVITREAL TRIAMCINOLONE ACE-
tonide (Kenalog, Bristol-Myers Squibb, New York, New York, USA) is a common treatment for a variety of vitreoretinal diseases. Although it has been shown that triamcinolone acetonide can cause a delayed increase in intraocular pressure (IOP), the change in IOP within one week after injection has not been investigated. We report the effect of 4 mg intravitreal triamcinolone acetonide on IOP in the first week after injection. Approval from the Institutional Review Board of the University of Chicago was obtained before initiating this Accepted for publication Aug 22, 2006. From the University of Chicago School of Medicine, Department of Ophthalmology and Visual Science, Chicago, Illinois (E.W.L., S.M.H., W.F.M.); Illinois Eye Institute, Chicago, Illinois (T.L.N.); and Washington University in St Louis School of Medicine, Department of Ophthalmology and Visual Science, Barnes Retina Institute, St Louis, Missouri (R.S.A.). Inquiries to Seenu M. Hariprasad, MD, Department of Ophthalmology and Visual Science, University of Chicago, 5841 South Maryland, MC 2114, Chicago, IL 60637; e-mail: [email protected]
BRIEF REPORTS
365
FIGURE. Short-term intraocular pressure (IOP) changes after intravitreal triamcinolone injection. Graph illustrates preinjection IOP and postinjection IOP at 30 minutes, one to two days, and five to seven days after injection.
study. We performed a retrospective chart review of 43 patients who underwent 50 consecutive intravitreal injections of 4 mg (0.1 ml of 40 mg/ml) triamcinolone acetonide at the University of Chicago Retina Clinic. Preinjection IOP (within one hour of the injection) and postinjection IOP (at 30 minutes, one to two days, and five to seven days) were recorded. All IOPs were obtained by Goldmann applanation tonometry. Mean preinjection IOP was 14.60 ⫾ 3.71 mm Hg (mean ⫾ SD) (range, 9 to 26 mm Hg). Mean postinjection IOP (approximately 30 minutes after injection) was 19.64 ⫾ 7.43 mm Hg (range, 5 to 45 mm Hg). Mean IOP change before and after injection was 4.83 ⫾ 7.10 mm Hg. The mean IOP one to two days after injection was 15.32 ⫾ 4.41 mm Hg (range, 6 to 27 mm Hg). The mean IOP at five to seven days after injection was 15.94 ⫾ 4.86 mm Hg (range, 5 to 28 mm Hg) (Figure). None of the patients was treated with topical IOPlowering medications after injection. Paracentesis to lower IOP was not required in any patient. Two patients had pressures ⬎30 mm Hg within 30 minutes after injection. Over the course of an hour, the IOP normalized in these two patients to the mid-20s without pharmacologic intervention. In one patient, digital massage was implemented. At one week, the IOP was ⬍20 mm Hg in both of these patients. Although it is well established that intravitreal triamcinolone acetonide can cause a marked increase in IOP several weeks after injection as a result of so-called steroid response, the short-term IOP trends within the first week have not been clearly identified.1–5 The results of our study suggest that intravitreal triamcinolone acetonide does not 366
AMERICAN JOURNAL
cause a sustained increase in IOP within the first week after injection. A transient increase in IOP ⬎30 mm Hg was seen in two patients; however, this normalized within one hour without pharmacologic or surgical intervention. Benz and associates6 recently reported that IOP changes within the initial 30 minutes after intravitreal triamcinolone acetonide injection correlate with the presence of vitreous reflux. In their study, patients who were noted to have no vitreous reflux after injection had a marked increase in mean IOP, which normalized within 30 minutes. Patients who were noted to have vitreous reflux did not have an increase in mean IOP within 30 minutes of the injection. Our findings are consistent with theirs. Our study further demonstrates that the mean IOP does not greatly change from baseline within one week after injection. Singh and associates7 described a case series of three patients who experienced an early rapid increase in IOP approximately four to seven days after intravitreal triamcinolone acetonide injection. It was speculated this was due to migration of triamcinolone acetonide particles into the trabecular meshwork. These cases required filtration surgery to achieve pressure control. Notably, all these patients were pseudophakic. Our study did not have any patients with a sustained increased of IOP at one week. However, it may be prudent to check patients’ IOP within the first week after injection to avoid possible, albeit rare, uncontrolled glaucoma in pseudophakes. On the basis of our results, pharmacologic or surgical intervention is not necessary for an increase in IOP within the first day after intravitreal triamcinolone acetonide injection. We advise against paracentesis for IOP increased within OF
OPHTHALMOLOGY
FEBRUARY 2007
this time frame because this procedure is associated with complications such as lens damage, patient discomfort, and theoretical risk of increased infection. Additionally, it may not be necessary for the patient to remain at the clinic immediately after intravitreal injection for an IOP check. THIS STUDY WAS SUPPORTED BY AN UNRESTRICTED GRANT from the Research to Prevent Blindness, Inc, New York, New York. The authors indicate no financial conflict of interest. Involved in design of study (E.L., S.H., W.M., R.A.) collection, management, analysis and interpretation of data, and preparation of the data (E.L., S.H., W.M., R.A.); involved in collection of data (E.L., S.H., T.N.); and involved in the review, approval, and preparation of the manuscript (E.L., S.H., T.N., W.M., R.A.). REFERENCES
1. Jonas JB, Degenring RF, Kreissig I, Akkoyun I, Kamppeter BA. Intraocular pressure elevation after intravitreal triamcinolone acetonide injection. Ophthalmology 2005;112:593–598. 2. Smithen LM, Ober MD, Maranan L, Spaide RF. Intravitreal triamcinolone acetonide and intraocular pressure. Am J Ophthalmol 2004;138:740 –743. 3. Wingate RJ, Beaumont PE. Intravitreal triamcinolone and elevated intraocular pressure. Aust N Z J Ophthalmol 1999; 27:431– 432. 4. Jonas JB, Kreissig I, Degenring R. Intraocular pressure after intravitreal injection of triamcinolone acetonide. Br J Ophthalmol 2003;87:24 –27. 5. Kreissig I, Degenring RF, Jonas JB. Intraocular pressure after intravitreal triamcinolone acetonide. Ophthalmologe 2005; 102:153–157. 6. Benz MS, Albini TA, Holz ER, et al. Short-term course of intraocular pressure after intravitreal injection of triamcinolone acetonide. Ophthalmology 2006;113:1174 –1178. 7. Singh IP, Ahmad SI, Yeh D, et al. Early rapid rise in intraocular pressure after intravitreal triamcinolone acetonide injection. Am J Ophthalmol 2004;138:286 –287.
Strong Association Between HLA-A*0206 and Stevens-Johnson Syndrome in the Japanese Mayumi Ueta, MD, PhD, Chie Sotozono, MD, PhD, Katsushi Tokunaga, PhD, Toshio Yabe, PhD, and Shigeru Kinoshita, MD, PhD To investigate the association between HLA class I antigens and Stevens-Johnson syndrome (SJS)/
PURPOSE:
Accepted for publication Sept 12, 2006. From the Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kawaramachi, Kamigyo-ku, Kyoto, Japan (M.U., C.S., S.K.); the Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan (K.T.); and the Tokyo Metropolitan Red Cross Blood Center, Tatumi, Koutou-ku, Tokyo, Japan (T.Y.). Inquiries to Mayumi Ueta, MD, PhD, Department of Ophthalmology, Kyoto Prefectural University of Medicine, 465 Kajiicho, Hirokoji, Kawaramachi, Kamigyoku, Kyoto 602-0841, Japan; e-mail: mueta@ophth. kpu-m.ac.jp
VOL. 143, NO. 2
toxic epidermal necrolysis (TEN) with ocular complications in Japanese. DESIGN: Case-control study. METHODS: We examined the histocompatibility antigen genes HLA-A, -B, and -C of 40 Japanese SJS/TEN patients with ocular complications and 113 healthy Japanese volunteers by polymerase chain reaction amplification and subsequent hybridization with sequencespecific oligonucleotide probes (PCR-SSO). RESULTS: We clarified that HLA-A*0206 is strongly associated with SJS/TEN with ocular complications in the Japanese. CONCLUSIONS: Because this finding is completely different from data reported elsewhere on Taiwanese Han Chinese patients and Caucasian patients, it suggests strong ethnic differences in the HLA-SJS association and points to the need for studies in other ethnic populations in order to obtain a global picture. (Am J Ophthalmol 2007;143: 367–368. © 2007 by Elsevier Inc. All rights reserved.)
S
TEVENS-JOHNSON SYNDROME (SJS) AND TOXIC EPIDER-
mal necrolysis (TEN) are acute-onset mucocutaneous diseases induced by infectious agents and/or inciting drugs. Based on a large international case-control study, SJS and TEN are considered as severity variants of a single entity1; developing acute exanthema that progresses to limited (SJS) or more widespread (TEN) blistering and erosion of the skin and mucous membranes. Although rare, these reactions carry high morbidity and mortality rates. Ophthalmologists recognize the serious ocular complications leading to severe, lifelong visual dysfunction. Conjunctival invasion into the cornea attributable to corneal epithelial stem cell deficiency progresses despite healing of the skin lesions, and corneal opacity, neovascularization, symblepharon, ankyloblepharon, and in some instances, keratinization, appears on the ocular surface at the chronic stage. Interestingly, we observed that more than 95% of three patients out of 61 SJS/TEN with ocular complications had lost their fingernails in the acute stage and transformed nails often continue even after healing of the skin lesions. The reported incidence of ocular complications is 50% to 69%. The pathobiological mechanisms underlying the onset of SJS/TEN have not been fully established, although the involvement of immune mechanisms and an altered drug metabolism have been suggested. Whatever the pathogenetic events, the extreme rarity of cutaneous and ocular surface reactions to drug therapies led us to suspect individual susceptibility. We studied the histocompatibility antigen genes HLA-A, -B, and -C of Japanese SJS/TEN patients with ocular complications. The study was approved by the institutional review board, and consent was obtained from all participants in written form. The diagnosis of SJS/TEN was based on a confirmed history of the acute onset of high fever, serious mucocutaneous illness with skin eruptions, and involvement of at least two mucosal sites including the
BRIEF REPORTS
367