- Email: [email protected]
Glistenings in foldable intraocular lenses1
Glistenings in foldable intraocular lenses Daniele Tognetto, MD, Lisa Toto, MD, Giorgia Sanguinetti, MD, Giuseppe Ravalico, MD Purpose: To evaluate the formation of glistenings in foldable intraocular lenses (IOLs) of various materials after cataract surgery. Setting: University Eye Clinic of Trieste, Trieste, Italy. Methods: In this prospective study, 273 patients were randomized to have implantation of 1 of 7 types of foldable IOLs in the capsular bag after phacoemulsification. The IOLs were the CeeOn姞 Edge 911A (Pharmacia & Upjohn Co.), ACR6D姞 (Corneal), AcrySof姞 (Alcon), SI-40NB (AMO), Hydroview姞 H60M (Storz), Sensar姞 (AMO), and Stabibag姞 (Ioltech). The presence of glistenings in the IOL optic was assessed by slitlamp evaluation 7, 30, 90, 180, 360, and 720 days after surgery. The glistenings were graded at each control. Results: Glistenings were observed in all IOL groups. The percentage of patients with glistenings ranged from 40.0% to 67.5%, with the percentage increasing up to 90 days after surgery and then becoming stable in most groups. The AcrySof group had a continuous increase over time. The mean grade of glistenings increased up to 180 days after surgery and then became stable in most groups. The AcrySof and 911A groups had a continuous increase over time. Conclusions: Glistening formation was observed in 7 different foldable IOLs. The AcrySof group had a higher percentage and a greater density of glistenings. J Cataract Refract Surg 2002; 28:1211–1216 © 2002 ASCRS and ESCRS
T
he advent of small-incision cataract surgery led to an increased interest in foldable intraocular lenses (IOLs). The development of new foldable IOLs of various materials and shapes is the subject of continuing research.1–3 In 1994, the AcrySof威 (Alcon), an acrylic nonhydrogel IOL, was released on the market. It introduced considerable technical innovations including a high refractive index, square edges, and slow, controlled unfolding resulting from its plasticity.1,4 – 8
Accepted for publication February 25, 2002. From the Eye Clinic, University of Trieste, Trieste, Italy. Presented at the Symposium on Cataract, IOL and Refractive Surgery, Boston, Massachusetts, USA, May 2000. None of the authors has a financial or proprietary interest in any material or method mentioned. Reprint requests to Daniele Tognetto, MD, Istituto di Clinica Oculistica, Universita` di Trieste, Ospedale Maggiore, Piazza Ospedale, 1, 34129 Trieste, Italy. E-mail: [email protected]. © 2002 ASCRS and ESCRS Published by Elsevier Science Inc.
Several studies report the appearance of small intralenticular vacuoles in some IOLs. These vacuoles, termed glistenings because of their clinical appearance, have been noticed in the first weeks after IOL implantation.9 –15 According to various authors, glistenings are caused by water vacuoles visible because of differences in the refractive index. Reports say that the glistenings do not affect visual function or cause visual disturbances such as decreased contrast sensitivity, induced glare, or decreased visual acuity except in the most severe cases.15,16 Glistenings have been related to temperature changes in the IOL optic, especially in association with the AcryPak packaging system of AcrySof IOLs, and to modification of aqueous humor components.11,14 Intralenticular glistenings have been described as a phenomenon peculiar to AcrySof IOLs. However, glistenings were first reported in 1984 by Ballin,17 who describes the appearance of glistenings in an IOL with a poly(methyl methacrylate) (PMMA) optic. We have occasionally observed glistenings in IOLs of material other 0886-3350/02/$–see front matter PII S0886-3350(02)01353-6
GLISTENINGS IN FOLDABLE IOLS
than AcrySof. Thus, we wondered whether glistenings were not distinctive to AcrySof but are present in other materials as well. This study assessed the presence and the grade of glistenings in foldable IOLs of various materials after phacoemulsification and capsular bag implantation.
Patients and Methods This prospective randomized study comprised 273 consecutive cataract patients (273 eyes) referred to the University of Trieste Eye Clinic from January 1998 to March 1999. All patients had standardized small-incision phacoemulsification with IOL implantation in the capsular bag. Exclusion criteria were other ocular pathologies, previous anterior or posterior segment surgery, intraoperative or postoperative complications, diabetes, and systemic therapy with antiinflammatory agents. Patients were randomized to receive 1 of the following foldable IOLs: CeeOn威 Edge 911A (Pharmacia & Upjohn Co.), n ⫽ 39; ACR6D威 (Corneal) , n ⫽ 36; AcrySof, n ⫽ 41; SI-40NB威 (AMO), n ⫽ 45; Hydroview威 H60M (Storz), n ⫽ 36; Sensar威 (AMO), n ⫽ 42; Stabibag威 (Ioltech), n ⫽ 34. The randomization list was generated by random permutation of the 7 IOLs in each consecutive block. The mean age of patients was 76.21 years ⫾ 5.02 (SD) in the 911A group, 74.17 ⫾ 5.42 years in the ACR6D group, 74.81 ⫾ 5.82 years in the AcrySof group, 73.95 ⫾ 5.92 years in the SI-40NB group, 75.03 ⫾ 5.82 years in the Hydroview group, 75.93 ⫾ 5.11 years in the Sensar group, and 74.53 ⫾ 5.58 years in the Stabibag group. There were no statistically significant age differences among groups. All operations were performed by the same surgeon (D.T.) using the same technique. After a 3.2 mm near-clear corneal tunnel was made, a 4.5 to 5.0 mm capsulorhexis was created. Phacofracture in the capsular bag and automated irrigation/aspiration of the cortical remnants were performed. The IOL was implanted in the capsular bag and the incision closed with a single 10-0 nylon suture. Sodium hyaluronate 1.4% (Healon GV威) was used before the capsulorhexis was created and sodium hyaluronate 1.0% (Provisc威), before IOL implantation. All IOLs were implanted with a forceps except the Sensar, which was implanted with the AMO Unfolder Sapphire series. All patients received the same preoperative and postoperative treatment. Sodium diclofenac 0.1% and ofloxacin 0.3% eyedrops were instilled 4 times the day before and the morning of surgery. The pupil was dilated with topical tropicamide 0.5% and phenylephrine 10%. At the end of surgery, 4 mg of betamethasone was administered subconjunctivally. After surgery, dexamethasone 0.2% eyedrops were instilled 4 times daily for 2 weeks and then sodium diclofenac 0.1% eyedrops 4 times daily for 2 months. 1212
Twenty-four of the 273 patients recruited in the study dropped out; 22 because of a lack of cooperation and 2 because of intraoperative complications (capsule rupture and iris bleeding). Thirty-three of the remaining 249 patients were in the 911A group, 36 in the ACR6D group, 37 in the AcrySof group, 41 in the SI-40NB group, 32 in the Hydroview group, 40 in the Sensar group, and 30 in the Stabibag group. Patients were examined 7, 30, 90, 180, 360, and 720 days after surgery. Best corrected visual acuity (BCVA) was measured at each visit. After the pupil was dilated, the IOL optic was studied and the lens optic inspected for the presence of microvacuoles using slitlamp biomicroscopy. The observations were given a score on the following clinical scale: 0 ⫽ absence, 1 ⫽ traces (countable vacuoles), 2 ⫽ moderate (low density of uncountable vacuoles), and 3 ⫽ severe (high density of uncountable vacuoles). The data were recorded, and photographic images were captured at various magnifications using a photographic slitlamp. Data were expressed as the percentage of IOLs with glistenings and the mean grade of glistenings at each control. Statistical analysis was done by comparing the presence and grade of glistenings at 7, 30, 90, 180, 360, and 720 days. Age was analyzed using the t test. The Mann-Whitney test was used to compare BCVA, expressed as median and range. The n-way frequency and cross-tabulation tables with measures of association (proc freq/measures, SAS, 1988) were used to compare the presence of glistenings among the 7 groups. An analysis of variance for repeated measurements (proc glm, SAS, 1988) was used to compare the mean grades of glistenings among the 7 IOL groups.
Results Postoperatively, the median BCVA in all groups was 0.9 at 7 days and 0.8 at 720 days. The difference in BCVA among groups was not significant. Glistenings were present in all the IOLs (Figures 1 to 7). The percentage of patients with glistenings increased up to 90 days after surgery and then became stable in the 911A, ACR6D, SI-40NB, Hydroview, Sensar, and Stabibag groups. The AcrySof group had a continuous increase over time. At the last 2 examinations, the difference between AcrySof IOLs and Sensar and Stabibag IOLs was statistically significant (P ⬍ .05) by n-way frequency and cross-tabulation tables with measures of association (Figure 8). The mean grade of glistenings increased up to 180 days after surgery and then became stable in the ACR6D, SI-40NB, Hydroview, Sensar, and Stabibag groups. The AcrySof and 911A groups had a continuous
J CATARACT REFRACT SURG—VOL 28, JULY 2002
GLISTENINGS IN FOLDABLE IOLS
Figure 1. (Tognetto) Glistenings in a Pharmacia 911A CeeOn
Figure 2. (Tognetto) Glistenings in a Corneal ACR6D IOL.
Edge IOL.
Figure 3. (Tognetto) Glistenings in an Alcon AcrySof IOL.
Figure 4. (Tognetto) Glistenings in an AMO SI-40NB IOL.
Figure 5. (Tognetto) Glistenings in a Storz Hydroview H60M IOL.
Figure 6. (Tognetto) Glistenings in an AMO Sensar IOL.
increase over time. When all the groups were considered, it was found that time had a significant influence on glistening formation (P ⬍ .005).
The IOL type had a significant effect on the grade of the glistenings. The mean grade was significantly higher in the AcrySof group than in the 911A group at 180,
J CATARACT REFRACT SURG—VOL 28, JULY 2002
1213
GLISTENINGS IN FOLDABLE IOLS
Figure 7. (Tognetto) Glistenings in an Ioltech Stabibag IOL. Note that the figure has been rotated 90 degrees to the right.
360, and 720 days (P ⬍ .01) and than all the other IOLs at 180 days (P ⬍ .005), 360 days (P ⬍ .001), and 720 days (P ⬍ .0001) (Figure 9). No IOL in the ACR6D, SI-40NB, Hydroview, Sensar, or Stabibag group had glistenings higher than grade 1. In the AcrySof and 911A groups, some IOLs had grade 2 glistenings. Grade 3 glistenings were not observed in any IOL.
Discussion Several authors have reported the appearance of glistenings in some AcrySof lenses9 –14 since these IOLs were first implanted. This phenomenon has always been considered to be specific to the AcrySof IOL and the
result of microscopic water vacuoles inside the IOL optic. However, glistenings were first described in a PMMA IOL,17 and Ibaraki and Yaguchi recently reported the first case of glistenings in a silicone IOL (N. Ibaraki, MD, C. Yaguchi, MD, “Glistenings in Silicone IOLs,” presented at the Symposium on Cataract, IOL and Refractive Surgery, Boston, Massachusetts, USA, May 2000). In our study, glistenings were present in all 7 foldable IOLs evaluated. To our knowledge, this is the first evidence of glistenings in a series of IOLs made of materials other than AcrySof such as silicone and hydrophilic and hydrophobic acrylic. Our results show that the occurrence of glistenings is significantly influenced by time. In most groups, glistening formation increased up to 180 days after surgery and then became stable, while in the AcrySof and 911A groups, a continuous increase over time was noted. The type of IOL seems to have a significant effect on glistenings. The percentage of IOLs with glistenings at the 2-year control ranged from 40.0% in the Sensar group to 67.5% in the AcrySof group. The mean grade of glistenings ranged from 0.40 in the Sensar group to 1.08 in the AcrySof group at the 2-year control. The AcrySof group had the highest percentage of IOLs with glistenings and the highest grade of glistenings at the last 3 examinations, confirming that glistenings were most common in AcrySof IOLs. Although glistenings can often occur as occasional phenomena, severe glistenings can impair visual acuity
Figure 8. (Tognetto) Percentage of patients with glistenings by IOL group over time.
1214
J CATARACT REFRACT SURG—VOL 28, JULY 2002
GLISTENINGS IN FOLDABLE IOLS
Figure 9. (Tognetto) Mean grade of glistenings by IOL group over time.
and contrast sensitivity.15,16 In our series, most IOLs had only trace glistenings. Only in the AcrySof and 911A groups did some IOLs have moderate glistenings. We did not observe glistening density severe enough to impair visual acuity in any IOL group. As there were not enough severe opacities in our series, contrast sensitivity was not tested. Further studies are needed to evaluate the impact of severe glistenings on vision and contrast sensitivity. Glistenings were first thought to be related to the AcryPak packaging system.14 This plastic folding device allowed the IOL to be folded without an instrument. Alcon suggested that the sterilization of the IOL within the plastic case could cause changes in the IOL optic, enabling microvacuole formation. These findings led Alcon to voluntarily withdraw the AcryPak system from the market. Other studies report glistenings in WagonWheel-packaged AcrySof IOLs, suggesting that packaging is not the only factor in the formation of glistenings.14 Omar and coauthors14 hypothesize that the formation of glistenings is related to temperature changes. These changes might increase the free volume in acrylic material, allowing vacuoles to form. These minute pockets would then be filled with aqueous humor, creating the typical shining appearance. In an in vitro study, Kato et al.9 found that glistenings appeared in a Wagon-Wheel-packaged AcrySof IOLs as the medium temperature decreased. They suggest that temperature changes induce spinodal decomposition of the swollen polymer network, with
consequent formation of microvacuoles consisting of water and loosely packed network chains. A possible relationship between the appearance of glistenings and the composition of the aqueous humor has been suggested by others. In a clinical study, Mitooka reported a higher incidence of glistenings in patients with diabetes mellitus than in nondiabetic patients (K. Mitooka, MD, et al., “Glistenings in Acrylic IOLs,” poster presented at the Symposium on Cataract, IOL and Refractive Surgery, Seattle, Washington, USA, April 1999). Blood–aqueous barrier (BAB) breakdown would seem to be involved in the formation of glistenings. In an in vitro study, Dick et al.11 related the occurrence of glistenings to the lipid and protein concentration in the aqueous humor. The deposition of phospholipids on the IOL optic would seem to reduce the IOL–aqueous surface tension, allowing the formation of glistenings and penetration of hydrophobic substances. This is enhanced by the hydrophobic nature of the IOL polymer. In our study, patients with pathologies predisposing to BAB breakdown were excluded. Moreover, glistenings have been observed in different IOL materials, both hydrophobic and hydrophilic. The etiology of these findings remains unclear. The cause of glistenings in IOLs appears to be multifactorial. Previous studies agree that the glistenings in AcrySof IOLs are the result of the presence of free water in a hydrophobic material. The observation of intralenticular opacities in IOLs of hydrophobic or hydrophilic material other than AcrySof suggests the possibility that not
J CATARACT REFRACT SURG—VOL 28, JULY 2002
1215
GLISTENINGS IN FOLDABLE IOLS
5.
6.
7.
Figure 10. (Tognetto) Glistenings aligned in the direction of the
8.
folding axis in an AcrySof IOL.
all opacities are necessarily water. Further studies must be done to evaluate all opacities as they might not be examples of the same phenomenon. We noted glistenings were aligned in the direction of the folding axis in some cases. We do not discard the possibility that the mechanical stress of folding maneuvers could play a part in the development of glistenings. This manipulation might cause microdamage to the IOL surface, especially in correspondence to areas directly in contact with the forceps, facilitating the formation of glistenings and aqueous humor penetration within the IOL (Figure 10). Further investigations are necessary to assess the incidence and the mechanism of glistening formation in patients with IOLs of different materials.
9.
10.
11.
12.
13.
References 1. Anderson C, Koch DD, Green G, et al. Alcon Acrysof™ acrylic intraocular lens. In: Martin RG, Gills JP, Sanders DR, eds, Foldable Intraocular Lenses. Thorofare, NJ, Slack, Inc, 1993; 161–177 2. Leaming DV. Practice styles and preferences of ASCRS members—1995 survey. J Cataract Refract Surg 1996; 22:931–939 3. Oshika T, Masuda K, Majima Y, et al. Current trends in cataract and refractive surgery in Japan—1995 survey. Jpn J Ophthalmol 1996; 40:419 – 433 4. Peng Q, Visessook N, Apple DJ, et al. Surgical prevention of posterior capsule opacification. Part 3: intraocular
1216
14.
15.
16.
17.
lens optic barrier effect as a second line of defense. J Cataract Refract Surg 2000; 26:198 –213 Nishi O, Nishi K, Sakanishi K. Inhibition of migrating lens epithelial cells at the capsular bend created by the rectangular optic edge of a posterior chamber intraocular lens. Ophthalmic Surg Lasers 1998; 29:587–594 Nishi O, Nishi K, Akura J, Nagata T. Effect of roundedged acrylic intraocular lenses on preventing posterior capsule opacification. J Cataract Refract Surg 2001; 27: 608 – 613 Nishi O, Nishi K, Wickstro¨ m K. Preventing lens epithelial cell migration using intraocular lenses with sharp rectangular edges. J Cataract Refract Surg 2000; 26:1543– 1549 Kruger AJ, Schauersberger J, Abela C, et al. Two year results: sharp versus rounded optic edges on silicone lenses. J Cataract Refract Surg 2000; 26:566 –570 Kato K, Nishida M, Yamane H, et al. Glistening formation in an AcrySof lens initiated by spinodal decomposition of the polymer network by temperature change. J Cataract Refract Surg 2001; 27:1493–1498 Christiansen G, Durcan FJ, Olson RJ, Christiansen K. Glistenings in the AcrySof intraocular lens: pilot study. J Cataract Refract Surg 2001; 27:728 –733 Dick HB, Olson RJ, Augustin AJ, et al. Vacuoles in the Acrysof™ intraocular lens as factor of the presence of serum in aqueous humor. Ophthalmic Res 2001; 33: 61– 67 Allers A, Baumeister M, Steinkamp GWK, et al. Intraindividueller Vergleich von Intraokularlinsen aus hochrefractiven Silikon und hydrophoben Acrykat (Alcon Acrysof MA60BM); 1-Jahresergebnisse. Ophthalmologe 2000; 97:669 – 675 Dogru M, Tetsumoto K, Tagami Y, et al. Optical and atomic force microscopy of an explanted AcrySof intraocular lens with glistenings. J Cataract Refract Surg 2000; 26:571–575 Omar O, Pirayesh A, Mamalis N, Olson RJ. In vitro analysis of AcrySof intraocular lens glistenings in AcryPak and Wagon Wheel packaging. J Cataract Refract Surg 1998; 24:107–113 Dhaliwal DK, Mamalis N, Olson RJ, et al. Visual significance of glistenings seen in the AcrySof intraocular lens. J Cataract Refract Surg 1996; 22:452– 457 Oshika T, Shiokawa Y, Amano S, Mitomo K. Influence of glistenings on the optical quality of acrylic foldable intraocular lens. Br J Ophthalmol 2001; 85:1034 –1037 Ballin N. Glistenings in injection-molded lens. (letter) Am Intra-Ocular Implant Soc J 1984; 10:473
J CATARACT REFRACT SURG—VOL 28, JULY 2002
T
he advent of small-incision cataract surgery led to an increased interest in foldable intraocular lenses (IOLs). The development of new foldable IOLs of various materials and shapes is the subject of continuing research.1–3 In 1994, the AcrySof威 (Alcon), an acrylic nonhydrogel IOL, was released on the market. It introduced considerable technical innovations including a high refractive index, square edges, and slow, controlled unfolding resulting from its plasticity.1,4 – 8
Accepted for publication February 25, 2002. From the Eye Clinic, University of Trieste, Trieste, Italy. Presented at the Symposium on Cataract, IOL and Refractive Surgery, Boston, Massachusetts, USA, May 2000. None of the authors has a financial or proprietary interest in any material or method mentioned. Reprint requests to Daniele Tognetto, MD, Istituto di Clinica Oculistica, Universita` di Trieste, Ospedale Maggiore, Piazza Ospedale, 1, 34129 Trieste, Italy. E-mail: [email protected]. © 2002 ASCRS and ESCRS Published by Elsevier Science Inc.
Several studies report the appearance of small intralenticular vacuoles in some IOLs. These vacuoles, termed glistenings because of their clinical appearance, have been noticed in the first weeks after IOL implantation.9 –15 According to various authors, glistenings are caused by water vacuoles visible because of differences in the refractive index. Reports say that the glistenings do not affect visual function or cause visual disturbances such as decreased contrast sensitivity, induced glare, or decreased visual acuity except in the most severe cases.15,16 Glistenings have been related to temperature changes in the IOL optic, especially in association with the AcryPak packaging system of AcrySof IOLs, and to modification of aqueous humor components.11,14 Intralenticular glistenings have been described as a phenomenon peculiar to AcrySof IOLs. However, glistenings were first reported in 1984 by Ballin,17 who describes the appearance of glistenings in an IOL with a poly(methyl methacrylate) (PMMA) optic. We have occasionally observed glistenings in IOLs of material other 0886-3350/02/$–see front matter PII S0886-3350(02)01353-6
GLISTENINGS IN FOLDABLE IOLS
than AcrySof. Thus, we wondered whether glistenings were not distinctive to AcrySof but are present in other materials as well. This study assessed the presence and the grade of glistenings in foldable IOLs of various materials after phacoemulsification and capsular bag implantation.
Patients and Methods This prospective randomized study comprised 273 consecutive cataract patients (273 eyes) referred to the University of Trieste Eye Clinic from January 1998 to March 1999. All patients had standardized small-incision phacoemulsification with IOL implantation in the capsular bag. Exclusion criteria were other ocular pathologies, previous anterior or posterior segment surgery, intraoperative or postoperative complications, diabetes, and systemic therapy with antiinflammatory agents. Patients were randomized to receive 1 of the following foldable IOLs: CeeOn威 Edge 911A (Pharmacia & Upjohn Co.), n ⫽ 39; ACR6D威 (Corneal) , n ⫽ 36; AcrySof, n ⫽ 41; SI-40NB威 (AMO), n ⫽ 45; Hydroview威 H60M (Storz), n ⫽ 36; Sensar威 (AMO), n ⫽ 42; Stabibag威 (Ioltech), n ⫽ 34. The randomization list was generated by random permutation of the 7 IOLs in each consecutive block. The mean age of patients was 76.21 years ⫾ 5.02 (SD) in the 911A group, 74.17 ⫾ 5.42 years in the ACR6D group, 74.81 ⫾ 5.82 years in the AcrySof group, 73.95 ⫾ 5.92 years in the SI-40NB group, 75.03 ⫾ 5.82 years in the Hydroview group, 75.93 ⫾ 5.11 years in the Sensar group, and 74.53 ⫾ 5.58 years in the Stabibag group. There were no statistically significant age differences among groups. All operations were performed by the same surgeon (D.T.) using the same technique. After a 3.2 mm near-clear corneal tunnel was made, a 4.5 to 5.0 mm capsulorhexis was created. Phacofracture in the capsular bag and automated irrigation/aspiration of the cortical remnants were performed. The IOL was implanted in the capsular bag and the incision closed with a single 10-0 nylon suture. Sodium hyaluronate 1.4% (Healon GV威) was used before the capsulorhexis was created and sodium hyaluronate 1.0% (Provisc威), before IOL implantation. All IOLs were implanted with a forceps except the Sensar, which was implanted with the AMO Unfolder Sapphire series. All patients received the same preoperative and postoperative treatment. Sodium diclofenac 0.1% and ofloxacin 0.3% eyedrops were instilled 4 times the day before and the morning of surgery. The pupil was dilated with topical tropicamide 0.5% and phenylephrine 10%. At the end of surgery, 4 mg of betamethasone was administered subconjunctivally. After surgery, dexamethasone 0.2% eyedrops were instilled 4 times daily for 2 weeks and then sodium diclofenac 0.1% eyedrops 4 times daily for 2 months. 1212
Twenty-four of the 273 patients recruited in the study dropped out; 22 because of a lack of cooperation and 2 because of intraoperative complications (capsule rupture and iris bleeding). Thirty-three of the remaining 249 patients were in the 911A group, 36 in the ACR6D group, 37 in the AcrySof group, 41 in the SI-40NB group, 32 in the Hydroview group, 40 in the Sensar group, and 30 in the Stabibag group. Patients were examined 7, 30, 90, 180, 360, and 720 days after surgery. Best corrected visual acuity (BCVA) was measured at each visit. After the pupil was dilated, the IOL optic was studied and the lens optic inspected for the presence of microvacuoles using slitlamp biomicroscopy. The observations were given a score on the following clinical scale: 0 ⫽ absence, 1 ⫽ traces (countable vacuoles), 2 ⫽ moderate (low density of uncountable vacuoles), and 3 ⫽ severe (high density of uncountable vacuoles). The data were recorded, and photographic images were captured at various magnifications using a photographic slitlamp. Data were expressed as the percentage of IOLs with glistenings and the mean grade of glistenings at each control. Statistical analysis was done by comparing the presence and grade of glistenings at 7, 30, 90, 180, 360, and 720 days. Age was analyzed using the t test. The Mann-Whitney test was used to compare BCVA, expressed as median and range. The n-way frequency and cross-tabulation tables with measures of association (proc freq/measures, SAS, 1988) were used to compare the presence of glistenings among the 7 groups. An analysis of variance for repeated measurements (proc glm, SAS, 1988) was used to compare the mean grades of glistenings among the 7 IOL groups.
Results Postoperatively, the median BCVA in all groups was 0.9 at 7 days and 0.8 at 720 days. The difference in BCVA among groups was not significant. Glistenings were present in all the IOLs (Figures 1 to 7). The percentage of patients with glistenings increased up to 90 days after surgery and then became stable in the 911A, ACR6D, SI-40NB, Hydroview, Sensar, and Stabibag groups. The AcrySof group had a continuous increase over time. At the last 2 examinations, the difference between AcrySof IOLs and Sensar and Stabibag IOLs was statistically significant (P ⬍ .05) by n-way frequency and cross-tabulation tables with measures of association (Figure 8). The mean grade of glistenings increased up to 180 days after surgery and then became stable in the ACR6D, SI-40NB, Hydroview, Sensar, and Stabibag groups. The AcrySof and 911A groups had a continuous
J CATARACT REFRACT SURG—VOL 28, JULY 2002
GLISTENINGS IN FOLDABLE IOLS
Figure 1. (Tognetto) Glistenings in a Pharmacia 911A CeeOn
Figure 2. (Tognetto) Glistenings in a Corneal ACR6D IOL.
Edge IOL.
Figure 3. (Tognetto) Glistenings in an Alcon AcrySof IOL.
Figure 4. (Tognetto) Glistenings in an AMO SI-40NB IOL.
Figure 5. (Tognetto) Glistenings in a Storz Hydroview H60M IOL.
Figure 6. (Tognetto) Glistenings in an AMO Sensar IOL.
increase over time. When all the groups were considered, it was found that time had a significant influence on glistening formation (P ⬍ .005).
The IOL type had a significant effect on the grade of the glistenings. The mean grade was significantly higher in the AcrySof group than in the 911A group at 180,
J CATARACT REFRACT SURG—VOL 28, JULY 2002
1213
GLISTENINGS IN FOLDABLE IOLS
Figure 7. (Tognetto) Glistenings in an Ioltech Stabibag IOL. Note that the figure has been rotated 90 degrees to the right.
360, and 720 days (P ⬍ .01) and than all the other IOLs at 180 days (P ⬍ .005), 360 days (P ⬍ .001), and 720 days (P ⬍ .0001) (Figure 9). No IOL in the ACR6D, SI-40NB, Hydroview, Sensar, or Stabibag group had glistenings higher than grade 1. In the AcrySof and 911A groups, some IOLs had grade 2 glistenings. Grade 3 glistenings were not observed in any IOL.
Discussion Several authors have reported the appearance of glistenings in some AcrySof lenses9 –14 since these IOLs were first implanted. This phenomenon has always been considered to be specific to the AcrySof IOL and the
result of microscopic water vacuoles inside the IOL optic. However, glistenings were first described in a PMMA IOL,17 and Ibaraki and Yaguchi recently reported the first case of glistenings in a silicone IOL (N. Ibaraki, MD, C. Yaguchi, MD, “Glistenings in Silicone IOLs,” presented at the Symposium on Cataract, IOL and Refractive Surgery, Boston, Massachusetts, USA, May 2000). In our study, glistenings were present in all 7 foldable IOLs evaluated. To our knowledge, this is the first evidence of glistenings in a series of IOLs made of materials other than AcrySof such as silicone and hydrophilic and hydrophobic acrylic. Our results show that the occurrence of glistenings is significantly influenced by time. In most groups, glistening formation increased up to 180 days after surgery and then became stable, while in the AcrySof and 911A groups, a continuous increase over time was noted. The type of IOL seems to have a significant effect on glistenings. The percentage of IOLs with glistenings at the 2-year control ranged from 40.0% in the Sensar group to 67.5% in the AcrySof group. The mean grade of glistenings ranged from 0.40 in the Sensar group to 1.08 in the AcrySof group at the 2-year control. The AcrySof group had the highest percentage of IOLs with glistenings and the highest grade of glistenings at the last 3 examinations, confirming that glistenings were most common in AcrySof IOLs. Although glistenings can often occur as occasional phenomena, severe glistenings can impair visual acuity
Figure 8. (Tognetto) Percentage of patients with glistenings by IOL group over time.
1214
J CATARACT REFRACT SURG—VOL 28, JULY 2002
GLISTENINGS IN FOLDABLE IOLS
Figure 9. (Tognetto) Mean grade of glistenings by IOL group over time.
and contrast sensitivity.15,16 In our series, most IOLs had only trace glistenings. Only in the AcrySof and 911A groups did some IOLs have moderate glistenings. We did not observe glistening density severe enough to impair visual acuity in any IOL group. As there were not enough severe opacities in our series, contrast sensitivity was not tested. Further studies are needed to evaluate the impact of severe glistenings on vision and contrast sensitivity. Glistenings were first thought to be related to the AcryPak packaging system.14 This plastic folding device allowed the IOL to be folded without an instrument. Alcon suggested that the sterilization of the IOL within the plastic case could cause changes in the IOL optic, enabling microvacuole formation. These findings led Alcon to voluntarily withdraw the AcryPak system from the market. Other studies report glistenings in WagonWheel-packaged AcrySof IOLs, suggesting that packaging is not the only factor in the formation of glistenings.14 Omar and coauthors14 hypothesize that the formation of glistenings is related to temperature changes. These changes might increase the free volume in acrylic material, allowing vacuoles to form. These minute pockets would then be filled with aqueous humor, creating the typical shining appearance. In an in vitro study, Kato et al.9 found that glistenings appeared in a Wagon-Wheel-packaged AcrySof IOLs as the medium temperature decreased. They suggest that temperature changes induce spinodal decomposition of the swollen polymer network, with
consequent formation of microvacuoles consisting of water and loosely packed network chains. A possible relationship between the appearance of glistenings and the composition of the aqueous humor has been suggested by others. In a clinical study, Mitooka reported a higher incidence of glistenings in patients with diabetes mellitus than in nondiabetic patients (K. Mitooka, MD, et al., “Glistenings in Acrylic IOLs,” poster presented at the Symposium on Cataract, IOL and Refractive Surgery, Seattle, Washington, USA, April 1999). Blood–aqueous barrier (BAB) breakdown would seem to be involved in the formation of glistenings. In an in vitro study, Dick et al.11 related the occurrence of glistenings to the lipid and protein concentration in the aqueous humor. The deposition of phospholipids on the IOL optic would seem to reduce the IOL–aqueous surface tension, allowing the formation of glistenings and penetration of hydrophobic substances. This is enhanced by the hydrophobic nature of the IOL polymer. In our study, patients with pathologies predisposing to BAB breakdown were excluded. Moreover, glistenings have been observed in different IOL materials, both hydrophobic and hydrophilic. The etiology of these findings remains unclear. The cause of glistenings in IOLs appears to be multifactorial. Previous studies agree that the glistenings in AcrySof IOLs are the result of the presence of free water in a hydrophobic material. The observation of intralenticular opacities in IOLs of hydrophobic or hydrophilic material other than AcrySof suggests the possibility that not
J CATARACT REFRACT SURG—VOL 28, JULY 2002
1215
GLISTENINGS IN FOLDABLE IOLS
5.
6.
7.
Figure 10. (Tognetto) Glistenings aligned in the direction of the
8.
folding axis in an AcrySof IOL.
all opacities are necessarily water. Further studies must be done to evaluate all opacities as they might not be examples of the same phenomenon. We noted glistenings were aligned in the direction of the folding axis in some cases. We do not discard the possibility that the mechanical stress of folding maneuvers could play a part in the development of glistenings. This manipulation might cause microdamage to the IOL surface, especially in correspondence to areas directly in contact with the forceps, facilitating the formation of glistenings and aqueous humor penetration within the IOL (Figure 10). Further investigations are necessary to assess the incidence and the mechanism of glistening formation in patients with IOLs of different materials.
9.
10.
11.
12.
13.
References 1. Anderson C, Koch DD, Green G, et al. Alcon Acrysof™ acrylic intraocular lens. In: Martin RG, Gills JP, Sanders DR, eds, Foldable Intraocular Lenses. Thorofare, NJ, Slack, Inc, 1993; 161–177 2. Leaming DV. Practice styles and preferences of ASCRS members—1995 survey. J Cataract Refract Surg 1996; 22:931–939 3. Oshika T, Masuda K, Majima Y, et al. Current trends in cataract and refractive surgery in Japan—1995 survey. Jpn J Ophthalmol 1996; 40:419 – 433 4. Peng Q, Visessook N, Apple DJ, et al. Surgical prevention of posterior capsule opacification. Part 3: intraocular
1216
14.
15.
16.
17.
lens optic barrier effect as a second line of defense. J Cataract Refract Surg 2000; 26:198 –213 Nishi O, Nishi K, Sakanishi K. Inhibition of migrating lens epithelial cells at the capsular bend created by the rectangular optic edge of a posterior chamber intraocular lens. Ophthalmic Surg Lasers 1998; 29:587–594 Nishi O, Nishi K, Akura J, Nagata T. Effect of roundedged acrylic intraocular lenses on preventing posterior capsule opacification. J Cataract Refract Surg 2001; 27: 608 – 613 Nishi O, Nishi K, Wickstro¨ m K. Preventing lens epithelial cell migration using intraocular lenses with sharp rectangular edges. J Cataract Refract Surg 2000; 26:1543– 1549 Kruger AJ, Schauersberger J, Abela C, et al. Two year results: sharp versus rounded optic edges on silicone lenses. J Cataract Refract Surg 2000; 26:566 –570 Kato K, Nishida M, Yamane H, et al. Glistening formation in an AcrySof lens initiated by spinodal decomposition of the polymer network by temperature change. J Cataract Refract Surg 2001; 27:1493–1498 Christiansen G, Durcan FJ, Olson RJ, Christiansen K. Glistenings in the AcrySof intraocular lens: pilot study. J Cataract Refract Surg 2001; 27:728 –733 Dick HB, Olson RJ, Augustin AJ, et al. Vacuoles in the Acrysof™ intraocular lens as factor of the presence of serum in aqueous humor. Ophthalmic Res 2001; 33: 61– 67 Allers A, Baumeister M, Steinkamp GWK, et al. Intraindividueller Vergleich von Intraokularlinsen aus hochrefractiven Silikon und hydrophoben Acrykat (Alcon Acrysof MA60BM); 1-Jahresergebnisse. Ophthalmologe 2000; 97:669 – 675 Dogru M, Tetsumoto K, Tagami Y, et al. Optical and atomic force microscopy of an explanted AcrySof intraocular lens with glistenings. J Cataract Refract Surg 2000; 26:571–575 Omar O, Pirayesh A, Mamalis N, Olson RJ. In vitro analysis of AcrySof intraocular lens glistenings in AcryPak and Wagon Wheel packaging. J Cataract Refract Surg 1998; 24:107–113 Dhaliwal DK, Mamalis N, Olson RJ, et al. Visual significance of glistenings seen in the AcrySof intraocular lens. J Cataract Refract Surg 1996; 22:452– 457 Oshika T, Shiokawa Y, Amano S, Mitomo K. Influence of glistenings on the optical quality of acrylic foldable intraocular lens. Br J Ophthalmol 2001; 85:1034 –1037 Ballin N. Glistenings in injection-molded lens. (letter) Am Intra-Ocular Implant Soc J 1984; 10:473
J CATARACT REFRACT SURG—VOL 28, JULY 2002