- Email: [email protected]
Late-onset toxic anterior segment syndrome
CASE REPORT
Late-onset toxic anterior segment syndrome Goichiro Miyake, MD, Ichiro Ota, MD, Kensaku Miyake, MD, Masahiro Zako, MD, PhD, Masayoshi Iwaki, MD, PhD, Akihiko Shibuya
We describe 6 cases that developed intraocular inflammation between 42 days and 137 days after implantation of an acrylic foldable intraocular lens (IOL) (ISert model 251) and failed to respond to antibiotic treatment. One eye required a vitrectomy and IOL removal, 2 eyes required irrigation of the capsule, and 5 eyes required systemic administration of steroids. The healing process took 30 to 108 days after onset. Simultaneous with our cases was an epidemic outbreak of sterile anterior segment inflammation with the same characteristics associated with the same IOL. The clinical features indicated late-onset toxic anterior segment syndrome. Analysis of the outbreak strongly suggested that toxicity of the aluminum used in the IOL production process was the cause. This contamination risk exists even with modern manufacturing technology. Financial Disclosure: Mr. Shibuya is an employee of Hoya Corporation Medical Division. No other author has a financial or proprietary interest in any material or method mentioned. J Cataract Refract Surg 2015; 41:666–669 Q 2015 ASCRS and ESCRS
Toxic anterior segment syndrome (TASS) is a type of sterile anterior segment inflammation that occurs after cataract extraction and intraocular lens (IOL) implantation surgery.1 Toxins of agents and instruments used intraoperatively are thought to be the cause of this syndrome.1 We describe 6 cases that presented symptoms similar to those of TASS; however, the time of onset and presumed cause led us to conclude the eyes experienced late-onset TASS. The anterior chamber cell flare grading reported by Hogan et al.2 is used in the case descriptions. CASE REPORTS The 6 eyes had senile cataract and had uneventful phacoemulsification and intracapsular implantation of a foldable
Submitted: October 17, 2014. Final revision submitted: November 27, 2014. Accepted: December 2, 2014. From the Department of Ophthalmology (G. Miyake, Zako, Iwaki), Aichi Medical University, Aichi, the Shohzankai Medical Foundation (G. Miyake, Ota, K. Miyake), Miyake Eye Hospital, Nagoya, and Hoya Corporation Medical Division (Shibuya), Tokyo, Japan. Corresponding author: Kensaku Miyake, MD, Shohzankai Medical Foundation, Miyake Eye Hospital, 3-15-68, Ozone, Kita-ku, Nagoya 462-0825 Japan. E-mail: [email protected].
666
Q 2015 ASCRS and ESCRS Published by Elsevier Inc.
acrylic IOL (iSert, model 251, Hoya Surgical Optics). Table 1 summarizes the findings, features, and treatments in each case.
Case 1 A 79-year-old woman presented with corneal edema and anterior flare and cells of grade 3 C accompanied by hypopyon. Chemosis and ciliary injection were relatively mild. The corrected distance visual acuity (CDVA) was 20/200 and the endothelial cell density (ECD), 2363 cells/mm2. Antibiotic eyedrops (2 months), subconjunctival injection of antibiotics (2 weeks), and intravenous (IV) administration of antibiotics (3 weeks) were started immediately. One day after the onset of symptoms, the anterior chamber was irrigated; the anterior aqueous culture was negative. The CDVA continued to decrease. Because the patient showed no improvement, vitrectomy was performed 1 week after the onset; the vitreous culture was negative. As the patient continued to show no improvement, the IOL with the lens capsule was removed. Thirty-five days after the onset, the symptoms and the CDVA began to improve. At 108 days, scleral suturing of the IOL was performed; the CDVA was 20/100 and the inflammation decreased. At the 11-month follow-up, the ECD was 1370 cells/mm2, a 42% decrease.
Case 2 A 75-year-old man presented with corneal edema, anterior flare and cells grade 3C, and mild ciliary injection. The CDVA was 20/200 and the ECD, 2560 cells/mm2. Antibiotic eyedrops, steroidal eyedrops, and subconjunctival injection of antibiotics were started immediately after the onset and continued for 10 days, but there was no improvement. The http://dx.doi.org/10.1016/j.jcrs.2015.01.002 0886-3350
CASE REPORT: LATE ONSET OF TASS
lens capsule was irrigated; the anterior aqueous culture was negative. At the time of this case, antibiotics were limited to eyedrops only; steroidal eyedrops were continued together with systemic administration of steroids (starting with six 5 mg prednisolone tablets) tapered over 45 days. Sixty-two days after the onset, the anterior inflammation resolved and the CDVA improved to 20/30. At the 10-month follow-up, the ECD was 15877 cells/mm2, a 38% decrease.
Case 3 A 86-year-old woman presented with confirmed flare and cells of grade 4C with fibrin and hypopyon. The ciliary injection was mild. The CDVA was 20/40 and the ECD, 2289 cells/mm2. Antibiotic eyedrops (35 days), steroidal and nonsteroidal antiinflammatory drug (NSAID) eyedrops (35 days), subconjunctival injection of antibiotics (14 days), and IV administration of antibiotics (10 days) were started immediately. Because the patient showed no improvement, the lens capsule was irrigated; the anterior chamber aqueous culture was negative. Fourteen days after the onset, systemic administration of steroids (8 prednisolone tablets initially) was started and tapered over 40 days. Anterior flare and cells gradually diminished and 42 days after the onset, the CDVA improved. At 58 days, flare and cells had almost completely resolved and the CDVA was 20/30. At the 12-month followup, the ECD was 1740 cells/mm2, a 24% decrease.
Case 4 A 69-year-old man presented with anterior flare and cells of grade 2C and slight corneal edema. The ciliary injection and chemosis were mild. The CDVA was 20/25 and the ECD, 2657 cells/mm2. Antibiotic eyedrops (1 week), subconjunctival injection of antibiotics (1 week), and IV administration of antibiotics (1 week) were started immediately. Four days after the onset, systemic administration of steroids (8 tablets daily for 40 days) was started. Anterior flare and cells remained at grade 2C at 2 weeks, decreased to grade 1C at 3 weeks, and had almost completely resolved by 4 weeks; the CDVA improved to 20/20. At the 12-month follow-up, the ECD was 2258 cells/mm2, a 15% decrease.
Case 5 A 46-year-old woman presented with anterior flare and cells of grade 2C and mild corneal edema. Ciliary injection was mild, and chemosis was not confirmed. The CDVA was 20/22 and the ECD, 2678 cells/mm2. Intravenous administration of antibiotics was started immediately and continued for 1 week, and systemic administration of steroids (8 tablets daily) was given for 4 weeks. Anterior flare and cells decreased to grade 1C at 1 week and resolved by 4 weeks; the CDVA improved to 20/15. At the 8-month follow-up, the ECD was 2348 cells/mm2, a 14% decrease.
Case 6 A 74-year-old woman presented with grade 2C anterior flare and cells and mild corneal edema. The CDVA was 20/29 and the ECD, 2864 cells/mm2. Steroidal and NSAID eyedrops were started immediately and continued for 2 months, and systemic administration of steroids was started (8 tablets initially) and tapered over 1 month. At 14 days, the anterior flare and cells decreased to grade 1C; the CDVA improved to 20/15. At 2 months, anterior flare and cells
667
had resolved. At the 7-month follow-up, the ECD was 2348 cells/mm2, an 18% decrease.
Laboratory Analysis From July to December 2012, the iSert IOL was implanted in 852 eyes at our surgical center and 6 eyes (0.7%) developed sterile anterior segment inflammation. At approximately the same time, there was an epidemic outbreak of sterile anterior segment inflammation in Japan associated with the same IOL. To determine the cause of the outbreak, the IOL manufacturer analyzed the residual ethylene oxide concentration of the IOLs and of the injector cartridge, as well as the bioburden and endotoxin level of the nonsterile products (ie, cartridge-coating material in the manufacturing process and IOL surface contaminants), the raw material extractables of the lens material, the polymerization processes, and the final products. In each quantitative analysis, the residual ethylene oxide concentration of the IOLs and injector cartridge was equal to or less than 10 mg/g, the endotoxin level of nonsterile products was equal to or less than 2.0 endotoxin unit/device, the IOL extractables were equal to or less than 0.1 absorbance, and the final products endotoxin level was equal to or less than 0.5 endotoxin unit/device. Next, the manufacturer checked the surface of 17 IOLs explanted from sterile anterior segment inflammation eyes in patients at an external testing center. A scanning electron microscope energy-dispersive X-ray detector (Figure 1) was used and found aluminum on the haptics of 11 IOLs. The aluminum in the washing fixture (ie, the device that fastens the IOL for washing), which adhered to the lens surface and exhibited toxicity, was identified as a potential cause. The speculation is that aluminum, the base material of the washing fixture that was covered with a polytetrafluoroethylene (PTFE) (Teflon) coating, adhered to the IOL haptics because the PTFE coating came off (Figure 2). A change in the IOL manufacturing process that occurred around the time of the epidemic and the prominent increase in sterile anterior segment inflammation associated with IOLs manufactured during this time further suggest that aluminum was the cause. To improve washing efficiency, the alumite coating had been changed to a PTFE coating, and this is thought to be related to the incidence of sterile anterior segment inflammation; only 75 of 340 266 eyes (0.022%) developed anterior segment inflammation before the coating was changed in October 2011. This incidence is not significantly different from the overall incidence of postoperative endophthalmitis in Japan. The incidence increased to 51 of 41 576 eyes (0.122%) during the time that both PTFE and alumite coatings were used and to 328 of 123 368 eyes (0.266%) when only the PTFE coating was used. The conclusion is that the toxicity of the aluminum in the washing fixtures caused the sterile anterior segment inflammation.
DISCUSSION We reported 6 cases of TASS that occurred 2 to 3 months after surgery, a significantly later onset than previously reported.1 Although 1 of the cases had a vitrectomy, the case is considered to have TASS because the eye failed to respond to antibiotic treatment, had no retinal vascular lesions, and
J CATARACT REFRACT SURG - VOL 41, MARCH 2015
668
CASE REPORT: LATE ONSET OF TASS
Table 1. Findings and treatments of the 6 cases.
Case
Time from Surgery to Onset (Days)
1
Slitlamp Biomicroscopic Findings Complaints
Corneal Edema
Flare/Cell2
Hypopyon
42
Heaviness sensation; blurred vision
CC
3
C
2
64
Mild ocular pain; blurred vision
CC
3
C
3
137
Mild ocular pain; blurred vision
CC
4
C
4
46
Mild burning sensation; blurred vision
C
3
d
5
45
Foreign-body sensation; blurred vision
C
2
d
6
70
Heaviness sensation; blurred vision
C
2
d
AMK Z amikacin sulfate; Bf Z bromfenac sodium hydrate 0.1%; CAZ Z ceftazidime hydrate; CMZ Z cefmenoxime hydrochloride; Df Z diclofenac sodium 0.1%; ED Z eyedrops; F Z fluorometholone 0.1%; IC Z intracapsular injection; IV Z intravenous injection; LVFX Z levofloxacin hydrate; OR Z oral administration; Pr Z prednisolone tablet (5 mg); SC Z subconjunctival injection; VCM Z vancomycin hydrochloride
eventually recovered the CDVA. An epidemic outbreak of late-onset TASS following implantation of the same IOL occurred in Japan during the same period as the case series we describe and is worth noting.
The IOL manufacturer conducted an analysis to determine the cause of the outbreak and concluded it to be aluminum in the washing fixture that detached and adhered to the IOL. In the early days of IOL implantation, the toxicity of residual polishing agents including silicone and aluminum on dry-packed IOLs was a clinically significant issue.3,4 Recent animal studies also suggest the toxicity of aluminum.5 In our report, aluminum was detected quantitatively from IOLs explanted due to delayed TASS. Although
Figure 1. A scanning electron microscopic finding of an IOL extracted because of sterile anterior segment inflammation (original magnification 500). Note the metal-like residues at the root of the IOL haptic (*). This site was analyzed using an energy-dispersive X-ray detector.
Figure 2. This X-ray analysis shows that among several peaks of residual materials such as carbon (C), oxygen (O), fluorine (F), copper (Cu), aluminum (Al), magnesium (Mg), silicon (Si), and platinum (Pt), the aluminum peak was notably high.
J CATARACT REFRACT SURG - VOL 41, MARCH 2015
669
CASE REPORT: LATE ONSET OF TASS
Table 1. (Cont.) Treatments
Time from Onset to Resolution (Days)
Follow-up to the Present (Mo)
Vitrectomy; IOL removal
108
11
Intralens capsular irrigation Intralens capsular irrigation
62
10
56
12
Antibiotics
Antiinflammatory
Surgical
ED: LVFX, CMZ SC: VCM, CAZ IV: VCM, CAZ IC: VCM, AMK ED: LVFX, CMZ SC: VCM, CAZ IC: VCM, AMK ED: VCM, CMZ SC: VCM, CAZ IV: VCM, CAZ IC: VCM, CAZ ED: VCM, CMZ SC: VCM, CAZ IV: VCM, AMK ED: VCM, CMZ SC: VCM, CAZ IV: VCM, AMK
ED: Bf, F, Df
ED: Bf, Df OR: Pr ED: Bf, Df OR: Pr
OR: Pr
d
32
12
ED: Bf OR: Pr
d
61
8
ED: Bf, Df OR: Pr
d
30
7
the toxicity of aluminum has been recognized,3–5 the degree of the toxicity varies depending on the amount and whether it is pure aluminium or alumina (oxidized aluminium). In our case series, the severity and duration of delayed TASS varied among the cases but are presumed to be associated with the amount of aluminum that adhered to the IOLs. The U.S. Food and Drug Administration recently developed a proactive TASS prevention program.6 The program involves steps such as assessment of potential causes of TASS using rabbits, methods for detecting relevant contaminants, improvement of clinical data collection, standardized testing of medical devices, and enhanced communication among participants. We believe the cases reported here and the epidemic outbreak could have been prevented by incorporating these steps.
2. Hogan MJ, Kimura SJ, Thygeson P. Signs and symptoms of uveitis. I. Anterior uveitis. Am J Ophthalmol 1959; 47(5, part 2):155–170 3. Alpar JJ, Fechner PU. Sterile endophthalmitisdtoxic lens syndrome. In: Alpar JJ, Fechner PU, eds, Fechner’s Intraocular Lenses. New York, NY, Thieme, 1986; 155–162 4. Meltzer DW. Sterile hypopyon following intraocular lens surgery. Arch Ophthalmol 1980; 98:100–104 5. Calogero D, Buchen SY, Tarver ME, Hilmantel G, Lucas AD, Eydelman MB. Evaluation of intraocular reactivity to metallic and ethylene oxide contaminants of medical devices in a rabbit model. Ophthalmology 2012; 119:e36–e42 6. Eydelman MB, Tarver ME, Calogero D, Buchen SY, Alexander KY. The Food and Drug Administration’s proactive toxic anterior segment syndrome program. Ophthalmology 2012; 119:1297–1302
REFERENCES 1. Mamalis N, Edelhauser HF, Dawson DG, Chew J, LeBoyer RM, Werner L. Toxic anterior segment syndrome. J Cataract Refract Surg 2006; 32:324–333
J CATARACT REFRACT SURG - VOL 41, MARCH 2015
First author: Goichiro Miyake, MD Department of Ophthalmology, Aichi Medical University, Aichi, Japan
Late-onset toxic anterior segment syndrome Goichiro Miyake, MD, Ichiro Ota, MD, Kensaku Miyake, MD, Masahiro Zako, MD, PhD, Masayoshi Iwaki, MD, PhD, Akihiko Shibuya
We describe 6 cases that developed intraocular inflammation between 42 days and 137 days after implantation of an acrylic foldable intraocular lens (IOL) (ISert model 251) and failed to respond to antibiotic treatment. One eye required a vitrectomy and IOL removal, 2 eyes required irrigation of the capsule, and 5 eyes required systemic administration of steroids. The healing process took 30 to 108 days after onset. Simultaneous with our cases was an epidemic outbreak of sterile anterior segment inflammation with the same characteristics associated with the same IOL. The clinical features indicated late-onset toxic anterior segment syndrome. Analysis of the outbreak strongly suggested that toxicity of the aluminum used in the IOL production process was the cause. This contamination risk exists even with modern manufacturing technology. Financial Disclosure: Mr. Shibuya is an employee of Hoya Corporation Medical Division. No other author has a financial or proprietary interest in any material or method mentioned. J Cataract Refract Surg 2015; 41:666–669 Q 2015 ASCRS and ESCRS
Toxic anterior segment syndrome (TASS) is a type of sterile anterior segment inflammation that occurs after cataract extraction and intraocular lens (IOL) implantation surgery.1 Toxins of agents and instruments used intraoperatively are thought to be the cause of this syndrome.1 We describe 6 cases that presented symptoms similar to those of TASS; however, the time of onset and presumed cause led us to conclude the eyes experienced late-onset TASS. The anterior chamber cell flare grading reported by Hogan et al.2 is used in the case descriptions. CASE REPORTS The 6 eyes had senile cataract and had uneventful phacoemulsification and intracapsular implantation of a foldable
Submitted: October 17, 2014. Final revision submitted: November 27, 2014. Accepted: December 2, 2014. From the Department of Ophthalmology (G. Miyake, Zako, Iwaki), Aichi Medical University, Aichi, the Shohzankai Medical Foundation (G. Miyake, Ota, K. Miyake), Miyake Eye Hospital, Nagoya, and Hoya Corporation Medical Division (Shibuya), Tokyo, Japan. Corresponding author: Kensaku Miyake, MD, Shohzankai Medical Foundation, Miyake Eye Hospital, 3-15-68, Ozone, Kita-ku, Nagoya 462-0825 Japan. E-mail: [email protected].
666
Q 2015 ASCRS and ESCRS Published by Elsevier Inc.
acrylic IOL (iSert, model 251, Hoya Surgical Optics). Table 1 summarizes the findings, features, and treatments in each case.
Case 1 A 79-year-old woman presented with corneal edema and anterior flare and cells of grade 3 C accompanied by hypopyon. Chemosis and ciliary injection were relatively mild. The corrected distance visual acuity (CDVA) was 20/200 and the endothelial cell density (ECD), 2363 cells/mm2. Antibiotic eyedrops (2 months), subconjunctival injection of antibiotics (2 weeks), and intravenous (IV) administration of antibiotics (3 weeks) were started immediately. One day after the onset of symptoms, the anterior chamber was irrigated; the anterior aqueous culture was negative. The CDVA continued to decrease. Because the patient showed no improvement, vitrectomy was performed 1 week after the onset; the vitreous culture was negative. As the patient continued to show no improvement, the IOL with the lens capsule was removed. Thirty-five days after the onset, the symptoms and the CDVA began to improve. At 108 days, scleral suturing of the IOL was performed; the CDVA was 20/100 and the inflammation decreased. At the 11-month follow-up, the ECD was 1370 cells/mm2, a 42% decrease.
Case 2 A 75-year-old man presented with corneal edema, anterior flare and cells grade 3C, and mild ciliary injection. The CDVA was 20/200 and the ECD, 2560 cells/mm2. Antibiotic eyedrops, steroidal eyedrops, and subconjunctival injection of antibiotics were started immediately after the onset and continued for 10 days, but there was no improvement. The http://dx.doi.org/10.1016/j.jcrs.2015.01.002 0886-3350
CASE REPORT: LATE ONSET OF TASS
lens capsule was irrigated; the anterior aqueous culture was negative. At the time of this case, antibiotics were limited to eyedrops only; steroidal eyedrops were continued together with systemic administration of steroids (starting with six 5 mg prednisolone tablets) tapered over 45 days. Sixty-two days after the onset, the anterior inflammation resolved and the CDVA improved to 20/30. At the 10-month follow-up, the ECD was 15877 cells/mm2, a 38% decrease.
Case 3 A 86-year-old woman presented with confirmed flare and cells of grade 4C with fibrin and hypopyon. The ciliary injection was mild. The CDVA was 20/40 and the ECD, 2289 cells/mm2. Antibiotic eyedrops (35 days), steroidal and nonsteroidal antiinflammatory drug (NSAID) eyedrops (35 days), subconjunctival injection of antibiotics (14 days), and IV administration of antibiotics (10 days) were started immediately. Because the patient showed no improvement, the lens capsule was irrigated; the anterior chamber aqueous culture was negative. Fourteen days after the onset, systemic administration of steroids (8 prednisolone tablets initially) was started and tapered over 40 days. Anterior flare and cells gradually diminished and 42 days after the onset, the CDVA improved. At 58 days, flare and cells had almost completely resolved and the CDVA was 20/30. At the 12-month followup, the ECD was 1740 cells/mm2, a 24% decrease.
Case 4 A 69-year-old man presented with anterior flare and cells of grade 2C and slight corneal edema. The ciliary injection and chemosis were mild. The CDVA was 20/25 and the ECD, 2657 cells/mm2. Antibiotic eyedrops (1 week), subconjunctival injection of antibiotics (1 week), and IV administration of antibiotics (1 week) were started immediately. Four days after the onset, systemic administration of steroids (8 tablets daily for 40 days) was started. Anterior flare and cells remained at grade 2C at 2 weeks, decreased to grade 1C at 3 weeks, and had almost completely resolved by 4 weeks; the CDVA improved to 20/20. At the 12-month follow-up, the ECD was 2258 cells/mm2, a 15% decrease.
Case 5 A 46-year-old woman presented with anterior flare and cells of grade 2C and mild corneal edema. Ciliary injection was mild, and chemosis was not confirmed. The CDVA was 20/22 and the ECD, 2678 cells/mm2. Intravenous administration of antibiotics was started immediately and continued for 1 week, and systemic administration of steroids (8 tablets daily) was given for 4 weeks. Anterior flare and cells decreased to grade 1C at 1 week and resolved by 4 weeks; the CDVA improved to 20/15. At the 8-month follow-up, the ECD was 2348 cells/mm2, a 14% decrease.
Case 6 A 74-year-old woman presented with grade 2C anterior flare and cells and mild corneal edema. The CDVA was 20/29 and the ECD, 2864 cells/mm2. Steroidal and NSAID eyedrops were started immediately and continued for 2 months, and systemic administration of steroids was started (8 tablets initially) and tapered over 1 month. At 14 days, the anterior flare and cells decreased to grade 1C; the CDVA improved to 20/15. At 2 months, anterior flare and cells
667
had resolved. At the 7-month follow-up, the ECD was 2348 cells/mm2, an 18% decrease.
Laboratory Analysis From July to December 2012, the iSert IOL was implanted in 852 eyes at our surgical center and 6 eyes (0.7%) developed sterile anterior segment inflammation. At approximately the same time, there was an epidemic outbreak of sterile anterior segment inflammation in Japan associated with the same IOL. To determine the cause of the outbreak, the IOL manufacturer analyzed the residual ethylene oxide concentration of the IOLs and of the injector cartridge, as well as the bioburden and endotoxin level of the nonsterile products (ie, cartridge-coating material in the manufacturing process and IOL surface contaminants), the raw material extractables of the lens material, the polymerization processes, and the final products. In each quantitative analysis, the residual ethylene oxide concentration of the IOLs and injector cartridge was equal to or less than 10 mg/g, the endotoxin level of nonsterile products was equal to or less than 2.0 endotoxin unit/device, the IOL extractables were equal to or less than 0.1 absorbance, and the final products endotoxin level was equal to or less than 0.5 endotoxin unit/device. Next, the manufacturer checked the surface of 17 IOLs explanted from sterile anterior segment inflammation eyes in patients at an external testing center. A scanning electron microscope energy-dispersive X-ray detector (Figure 1) was used and found aluminum on the haptics of 11 IOLs. The aluminum in the washing fixture (ie, the device that fastens the IOL for washing), which adhered to the lens surface and exhibited toxicity, was identified as a potential cause. The speculation is that aluminum, the base material of the washing fixture that was covered with a polytetrafluoroethylene (PTFE) (Teflon) coating, adhered to the IOL haptics because the PTFE coating came off (Figure 2). A change in the IOL manufacturing process that occurred around the time of the epidemic and the prominent increase in sterile anterior segment inflammation associated with IOLs manufactured during this time further suggest that aluminum was the cause. To improve washing efficiency, the alumite coating had been changed to a PTFE coating, and this is thought to be related to the incidence of sterile anterior segment inflammation; only 75 of 340 266 eyes (0.022%) developed anterior segment inflammation before the coating was changed in October 2011. This incidence is not significantly different from the overall incidence of postoperative endophthalmitis in Japan. The incidence increased to 51 of 41 576 eyes (0.122%) during the time that both PTFE and alumite coatings were used and to 328 of 123 368 eyes (0.266%) when only the PTFE coating was used. The conclusion is that the toxicity of the aluminum in the washing fixtures caused the sterile anterior segment inflammation.
DISCUSSION We reported 6 cases of TASS that occurred 2 to 3 months after surgery, a significantly later onset than previously reported.1 Although 1 of the cases had a vitrectomy, the case is considered to have TASS because the eye failed to respond to antibiotic treatment, had no retinal vascular lesions, and
J CATARACT REFRACT SURG - VOL 41, MARCH 2015
668
CASE REPORT: LATE ONSET OF TASS
Table 1. Findings and treatments of the 6 cases.
Case
Time from Surgery to Onset (Days)
1
Slitlamp Biomicroscopic Findings Complaints
Corneal Edema
Flare/Cell2
Hypopyon
42
Heaviness sensation; blurred vision
CC
3
C
2
64
Mild ocular pain; blurred vision
CC
3
C
3
137
Mild ocular pain; blurred vision
CC
4
C
4
46
Mild burning sensation; blurred vision
C
3
d
5
45
Foreign-body sensation; blurred vision
C
2
d
6
70
Heaviness sensation; blurred vision
C
2
d
AMK Z amikacin sulfate; Bf Z bromfenac sodium hydrate 0.1%; CAZ Z ceftazidime hydrate; CMZ Z cefmenoxime hydrochloride; Df Z diclofenac sodium 0.1%; ED Z eyedrops; F Z fluorometholone 0.1%; IC Z intracapsular injection; IV Z intravenous injection; LVFX Z levofloxacin hydrate; OR Z oral administration; Pr Z prednisolone tablet (5 mg); SC Z subconjunctival injection; VCM Z vancomycin hydrochloride
eventually recovered the CDVA. An epidemic outbreak of late-onset TASS following implantation of the same IOL occurred in Japan during the same period as the case series we describe and is worth noting.
The IOL manufacturer conducted an analysis to determine the cause of the outbreak and concluded it to be aluminum in the washing fixture that detached and adhered to the IOL. In the early days of IOL implantation, the toxicity of residual polishing agents including silicone and aluminum on dry-packed IOLs was a clinically significant issue.3,4 Recent animal studies also suggest the toxicity of aluminum.5 In our report, aluminum was detected quantitatively from IOLs explanted due to delayed TASS. Although
Figure 1. A scanning electron microscopic finding of an IOL extracted because of sterile anterior segment inflammation (original magnification 500). Note the metal-like residues at the root of the IOL haptic (*). This site was analyzed using an energy-dispersive X-ray detector.
Figure 2. This X-ray analysis shows that among several peaks of residual materials such as carbon (C), oxygen (O), fluorine (F), copper (Cu), aluminum (Al), magnesium (Mg), silicon (Si), and platinum (Pt), the aluminum peak was notably high.
J CATARACT REFRACT SURG - VOL 41, MARCH 2015
669
CASE REPORT: LATE ONSET OF TASS
Table 1. (Cont.) Treatments
Time from Onset to Resolution (Days)
Follow-up to the Present (Mo)
Vitrectomy; IOL removal
108
11
Intralens capsular irrigation Intralens capsular irrigation
62
10
56
12
Antibiotics
Antiinflammatory
Surgical
ED: LVFX, CMZ SC: VCM, CAZ IV: VCM, CAZ IC: VCM, AMK ED: LVFX, CMZ SC: VCM, CAZ IC: VCM, AMK ED: VCM, CMZ SC: VCM, CAZ IV: VCM, CAZ IC: VCM, CAZ ED: VCM, CMZ SC: VCM, CAZ IV: VCM, AMK ED: VCM, CMZ SC: VCM, CAZ IV: VCM, AMK
ED: Bf, F, Df
ED: Bf, Df OR: Pr ED: Bf, Df OR: Pr
OR: Pr
d
32
12
ED: Bf OR: Pr
d
61
8
ED: Bf, Df OR: Pr
d
30
7
the toxicity of aluminum has been recognized,3–5 the degree of the toxicity varies depending on the amount and whether it is pure aluminium or alumina (oxidized aluminium). In our case series, the severity and duration of delayed TASS varied among the cases but are presumed to be associated with the amount of aluminum that adhered to the IOLs. The U.S. Food and Drug Administration recently developed a proactive TASS prevention program.6 The program involves steps such as assessment of potential causes of TASS using rabbits, methods for detecting relevant contaminants, improvement of clinical data collection, standardized testing of medical devices, and enhanced communication among participants. We believe the cases reported here and the epidemic outbreak could have been prevented by incorporating these steps.
2. Hogan MJ, Kimura SJ, Thygeson P. Signs and symptoms of uveitis. I. Anterior uveitis. Am J Ophthalmol 1959; 47(5, part 2):155–170 3. Alpar JJ, Fechner PU. Sterile endophthalmitisdtoxic lens syndrome. In: Alpar JJ, Fechner PU, eds, Fechner’s Intraocular Lenses. New York, NY, Thieme, 1986; 155–162 4. Meltzer DW. Sterile hypopyon following intraocular lens surgery. Arch Ophthalmol 1980; 98:100–104 5. Calogero D, Buchen SY, Tarver ME, Hilmantel G, Lucas AD, Eydelman MB. Evaluation of intraocular reactivity to metallic and ethylene oxide contaminants of medical devices in a rabbit model. Ophthalmology 2012; 119:e36–e42 6. Eydelman MB, Tarver ME, Calogero D, Buchen SY, Alexander KY. The Food and Drug Administration’s proactive toxic anterior segment syndrome program. Ophthalmology 2012; 119:1297–1302
REFERENCES 1. Mamalis N, Edelhauser HF, Dawson DG, Chew J, LeBoyer RM, Werner L. Toxic anterior segment syndrome. J Cataract Refract Surg 2006; 32:324–333
J CATARACT REFRACT SURG - VOL 41, MARCH 2015
First author: Goichiro Miyake, MD Department of Ophthalmology, Aichi Medical University, Aichi, Japan