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Postsurgical inflammation after phacoemulsification and extracapsular extraction with soft or conventional intraocular lens implantation
Postsurgical inflammation after phacoemulsification and extracapsular extraction with soft or conventional intraocular lens implantation Tetsuro Oshika, M.D., Koichi Yoshimura, M.D., Norio Miyata, M.D. ' .'
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,', ABSTRACT prospective study was conducted in 120 patients to ::~s~¢$s .;tiietiine course of changes in intraocular inflammation after , ':i tlt~eellt3raet: strrgeryprQcedures: planned extracapsular extraction :·'.wi~~pply{Pt~h.ylmethacrylate) , (PMMA) intraocular lens (IOL) im;':~p!~d9_n(Ummincis.iongr.oup), phacoemulsificationwithPMMA :... lgl} mip:~~:JI.'~3ti~n(7ml1l 'incisiongroup), and phacoemulsificatiQn ::~th :f~lda.l?l~siUcone single-pieceIO L i'mplantation (4 mm incision ?,~~p.)-: :~chga;~~pwascarefullymatched for patients' ophthaltno:·;l()gj~ }ill\d, systel'nicbackgrounds. Patients with hard nuclei were : ~cl1;tded~ The degree ofiilflammation was evaluated by quantitatipg ,:;·;~qu~~1:li\1are .in'te~sityand cell count with the ~er flare-cell 'meter. ~~·.m1Jl.t,';~~tJyp~~t()perilti\(eperiod; both aqueous flare intensity and · ~I :£ount :were ; highest, in the II mm incision group followed, in .:.~ecf~{lS~gorder,bythe7 mmand 4 mm incisiongroups. Significant :. b¢~e¢Ji-grl)up differences were observed at one, two, and seven ·, p,oslQperativ.ed"ysf()l'fiare andone day through one week for cells. : ~o,thpilrame~ersineachgroup decreased to a similar level one .lli,Qnth3fter s~rgery,but flare intensity in all groups remained sig~iIicaijtlyhjgher than that of age-matched normal controls up to six ~~iltltspostoperatively. . -.-".:., Ac: Qne~y~ar
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' li~YWords~extr~capsular ' extraction, flare~cell meter, intraocular
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It is known that surgical trauma to the eye induces blood-aqueous barrier breakdown, leading to augmented protein leakage and cellular reaction in the aqueous humor. Modern cataract surgery, even with advances in surgical techniques and instrumentation and the efficacy of postsurgical remedies, can also induce this breakdown. In 1983, Sanders et aU demonstrated that a large penetrating limbal incision exerted a great degree of postsurgical blood-aqueous barrier breakdown using anterior segment fluorophotom-
etry in experimental surgical models. A morphological study in monkey eyes has shown that repeated paracentesis caused more severe disruption of the blood-aqueous barrier than a single paracentesis, 2 indicating that recurring ocular hypotony would result in greater damage to the barrier. These findings suggest that smaller incision cataract surgery, associated with a lower chance of ocular hypotony, may provoke a smaller degree of blood-aqueous barrier breakdown, helping to retain the postsurgical physiological environment within the eye.
From the Department of Ophthalmology, Tokyo Kosei Nenkin Hospital, Tokyo, japan (Oshika) and Miyata Eye Hospital, Miyazaki, japan (Yoshimura, Miyata). Presented in part at the Symposium on Cataract, IOL and Refractive Surgery, Boston, April 1991. Reprint requests to Tetsuro Oshika, MD" Department ofOphthalmology, Tokyo Kosei Nenkin Hospital, 5-1 Tsukudo-cho, Shinjuku-ku, Tokyo 162, japan. 356
J CATARACT REFRACT SURG-VOL 18, JULY 1992
Clinical observations indicate that phacoemulsification causes less postsurgical intraocular inflammation than planned extracapsular cataract extraction. 3 •4 However, no quantitative studies of the postsurgical inflammation and/or bloodaqueous barrier breakdown in these two procedures have been done. Despite the increasing interest in small incision cataract surgery using phacoemulsification and foldable intraocular lenses (IOLs), we do not know whether this new technique is more advantageous than the conventional techniques in lessening the degree of postoperative inflammation or quickening the process of blood-aqueous barrier re-establishment. We undertook the current study to assess the time course of changes in intraocular inflammation after cataract surgery performed by three procedures in groups of patients whose ophthalmologic and systemic backgrounds were as similar as possible. SUBJECTS AND METHODS Healthy patients scheduled for cataract extraction with posterior chamber IOL implantation were enrolled in the study. To enable random assignment of the patients to extracapsular extraction or phacoemulsification, those with a very hard and brunescent cataract, which was considered to be a contraindication of phacoemulsification,5,6 were excluded prior to initiating the study. Those who had any preoperative pathology which would confound the results were also excluded. Surgeries were performed using one of the following three procedures: (1) extracapsular cataract extraction and poly(methyl methacrylate) (PMMA) posterior chamber IOL implantation (11 mm incision group); (2) phacoemulsification and PMMA posterior chamber IOL implantation (7 mm incision group); (3) phacoemulsification and silicone posterior chamber IOL implantation (4 mm incision group). In Groups 1 and 2 (extracapsular extraction or phacoemulsification with PMMA IOL), the study was carried out in a randomized-parallel design; in Group 3 (phacoemulsification with silicone IOL) it was conducted in a similar group of patients at a later period because of the availability of the lens. Surgeries were performed by the authors in two facilities, Tokyo Kosei Nenkin Hospital (T.O.) and Miyata Eye Hospital (K.Y. and N.M.), from February 1989 to January 1990 for the PMMA lens series and from March to July 1990 for the silicone lens series. Ninety eyes of 90 patients fulfilling the criteria for cataract surgery were selected for the first series (Groups A and B). They were randomly assigned to the extracapsular extraction or phaco-
emulsification groups; 45 patients were in each group. The average age was 70.5 ± 1.2 and 71.3 ± 1.1 (mean ± SE) years, respectively. Randomization was done using a serial list of random numbers. In the extracapsular extraction group, nuclei were extracted through an 11 mm limbal incision after capsulorhexis. Following removal of residual cortex with an automated irrigation/aspiration unit, a 6.5 mm optic three-piece PMMA IOL (unmodified surface) was inserted into the capsular bag. Sodium hyaluronate was used to facilitate lens insertion and was aspirated as completely as possible at the end of surgery. The limbal incision was closed with a shoelace suture using 10-0 nylon. No patient received a peripheral iridectomy. Phacoemulsification was performed with capsulorhexis and emulsification of the nuclei in the posterior chamber. An IOL similar to the one in the extracapsular extraction group was inserted through a 7 mm incision into the capsular bag. Except for the method of nuclei removal and incision size, the surgical techniques were the same as in the extracapsular extraction procedure. The latter series (Group C) included 30 eyes of an additional 30 patients (71.1 ± 1.0 years) having phacoemulsification and silicone single-piece IOL implantation. The same admission criteria as in the previous series was applied for the selection of patients, and no significant difference in patient age between the two series was found. Following capsulorhexis and in situ emulsification of the nuclei, the cortex was removed with an automated irrigation/aspiration unit. The IOL was inserted into the capsular bag through a 4 mm limbal incision using a silicone lens injector. The wound was closed with a single 10-0 horizontal suture. Other surgical techniques were similar to those used in the first series. Patients in each group received the same routine preoperative and postoperative medications. Preoperative pupillary dilation was accomplished using topical 5% phenylephrine, 0.5% tropicamide, and 0.5% indomethacin, each given three times with a 30 minute interval between applications. Postoperative medications included topical 0.1 % betamethasone and 0.3% ofloxacin three times a day for two to three months. An anti prostaglandin agent, i.e., 0.5% indomethacin, was also instilled twice daily for one week and once daily thereafter up to two months. No steroids were injected subconjunctivally at the end of or after surgery. Patients were excluded if they, because of preoperative or postoperative intraocular pressure elevation, were treated by topical or systemic ocular hypotensive agents, which are known to affect
J CATARACT REFRACT SURG-VOL 18, JULY 1992
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aqueous flare intensity (aqueous protein concentration).7-Y Flare intensity and cell count in the aqueous humor were measured with the laser flare-cell meter; this apparatus and sensitivity have been described elsewhere. 10 -I.5 Measurements were taken before surgery (baseline) and 1, 2, 3 days, 1,2 weeks, and 1, 3, 6, and 12 months after surgery. Each measurement was made 30 to 60 minutes after topical application of O.S% phenylephrine and O.S% tropicamide. 16 Fifteen normal volunteers (7l.0 ± l.S years) were recruited to serve as age-matched controls (30 eyes). They received topical mydriatics and were measured with the laser flare-cell meter 30 minutes after instillation.) 6 Obtained data for flare intensity and cell count were compared among groups by the Friedman rank test of variance to test the null hypothesis that there was no difference among procedures. Specific differences in mean values between groups were tested for significance with the Wilcoxon rank-sum test.
RESULTS One hundred twenty patients entered the study. One patient in the 11 mm incision group and one in the 4 mm incision group were excluded because of surgical complications. After surgery, four patients were treated with ocular hypotensive agents for raised intraocular pressure. According to the protocol, studies in these cases were discontinued and the data were discarded. During the one-year postoperative course of the study, a few patients missed some of the predetermined follow-up visits . Eleven patients, who failed to appear on more than three occasions of nine scheduled examination periods, were eventually excluded from our analysis. Data from the remaining 103 patients were collected and analyzed: 39 eyes in the 11 mm incision group (extracapsular extraction and PMMA lens), 38 in the 7 mm incision group (phacoemulsification and PMMA lens), and 26 in the 4 mm incision group (phacoemulsification and silicone lens). Figure 1 compares preoperative and postoperative flare intensity in each group. Preoperative flare values were 6.2 ± 0.4,6.0 ± 0.3, and 6.4 ± 0.3 (mean ± SE) photon count/msec for the 11 mm, 7 mm and 4 mm incision groups, respectively; these were comparable to those of the age-matched normal controls, 6.3 ± 0.2 photon count/msec. In the immediate postoperative period, the 11 mm incision group had the highest flare intensity, followed, in decreasing order, by the 7 mm and 4 mm incision groups. Significant differences among the 358
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(Oshika) Changes in aqueous flare intensity follOWing cataract surgery performed with different procedures: 11 mm-planned extracapsular extraction with PMMA lens implantation; 7 mm-phacoemulsification with PMMA lens implantation; 4 mmphacoemulsification with silicone single-piece lens implantation; control-age-matched normal controls .
three procedures were observed at one and two days and one week postoperatively (Table 1). Flare intensity in each group decreased to a similar level one month after surgery. However, values remained significantly higher than those of the normal controls until three months postoperatively (P < .01). At the 6 and 12 month postoperative examinations, this difference was not statistically apparent. Postoperative cell count exhibited a tendency similar to that ofthe flare measurements (Figure 2). There were significant between-group differences from the first postoperative day and these persisted through one week after surgery (Table 1). No significant differences were noted at the one month and later observation periods. . Following the initial high flare intensity and cell count immediately after surgery, both parameters declined steadily. But flare intensity in the 4 mm incision group (silicone lens) displayed a slight rebound at two weeks postoperatively, forming a small second peak which was significantly higher than the values at one week postoperatively (P < .OS). DISCUSSION The current study compared the degree of intraocular inflammation after three different procedures of cataract surgery. Because of different methods of nucleus removal and dissimilar IOL materials in each group, the data obtained may not directly reflect the influence of incision size and/or
J CATARACT REFRACT SURG-VOL 18, JULY 1992
Table 1. Statistical analysis of Hare intensity and cell count. Flare Intensity Time Period Preoperative
Variance
Cell Count
11 mm7 mm
11 mm4 mm
7mm4mm
Variance
11 mm7mm
11 mm4mm
7mm4mm
P < .001
P < .05
P < .001
P< .01
P < .001
N.S.
P < .001
N.S.
P< .01
P< .05
P < .001
P< .05
P< .01
P< .05
P< .01
P< .05
P< .01
P < .01
P< .01
N.S.
N.S.
N.S.
1 day
P < .001
P < .001
2 days
P< .01
P < .01
3 days
N.S.
1 week
P< .05
2 weeks
N.S.
N.S.
1 month
N.S.
N.S.
N.S.
P < .01
N.S.
2 months
N.S.
N.S.
3 months
N.S.
N.S.
6 months
N.S.
N.S.
12 months
N.S.
N.S.
N.S.: Not significant.
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Fig. 2.
(Oshika) Changes in cell count following cataract surgery performed with different procedures: 11 mm-planned extracapsular extraction with PMMA lens implantation; 7 mm-phacoemulsification with PMMA lens implantation; 4 mm-phacoemulsification with silicone single-piece lens implantation.
surgical techniques on postoperative inflammation. For a more precise and controlled assessment of these factors, studies using identical lens material and surgical techniques would be required. Nevertheless, we did not feel it practical to perform phacoemulsification with IOL implantation through an 11 mm incision or to insert a foldable lens through a 7 mm or greater incision. Moreover, the present study was conducted to evaluate three standard surgical procedures, involving their peculiar surgical techniques and lens materials as part of the procedures. Thus, the authors used their routine surgical techniques with only minor mod-
ifications to obtain possible congruence among groups. One special consideration in designing this study was that patients with a very hard nuclei contraindicated for phacoemulsification were excluded to match the ophthalmologic and systemic backgrounds of the patients in each group . Results of the present study demonstrated that immediate postoperative inflammation was significantly greater in the larger incision surgery groups. Statistically significant differences were observed at one, two, and seven postoperative days for flare intensity and one day through one week for cell count_ There are at least two possible explanations for this result: (I) The longer corn eoscleral wound provoked a greater degree of irritation to the uveal tissues, leading to a subsequent increase in the synthesis of inflammatory mediators. (2) The wider limbal opening induced a greater extent of ocular hypotony, which is known to result in a reflux of serum components via the trabecular meshwork into the anterior chamber 17 - 2o and/or disruption of the bloodaqueous barrieL2.19-22 This second postulate is plausible because extraction of the whole nuclei through a large limbal incision commonly leads to collapse and hypotony of the anterior chamber. Procedures using smaller incisions would better avoid intraoperative ocular hypotony by maintaining the configuration of the globe and allowing the least amount of fluid leakage through the wound. At the one month and later postoperative observation periods, no significant differences in either aqueous flare intensity or cell count among the three groups were found. This suggests that no
J CATARACT REFRACT SURG-VOL 18, JULY 1992
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clinically apparent difference in long-term influence on the blood-aqueous barrier function exists between the procedures. We were interested in the finding that flare intensity in all surgery groups remained at levels higher than those of age-matched normal controls and preoperative baseline measurements until six months postoperatively. This result, which agrees with previous fl uorophotometric studies,23-26 indicates that blood-aqueous barrier function is not completely re-established for a long period after surgery. Small incision cataract surgery using phacoemulsification and a foldable IOL has several clinically proven advantages over larger incision surgery, 27 -30 including reduction of induced astigmatism, better uncorrected visual acuity, earlier stabilization of refraction, and more rapid healing. In view of these findings and the present results, it appears that smaller incision surgery allows faster physical and visual rehabilitation. As shown in the results, flare intensity in the silicone lens group rebounded two weeks after surgery, although this change was not clinically significant. Our previous study using a hydrogel IOL revealed an identical phenomenon at the same postoperative period. 31 Silicone and hydrogel share the physical characteristics of high biocompatibility, which results in the lack of adhesion between the lens and surrounding ocular tissues. It might be that this feature of both soft materials had played a role in producing the rebound of flare intensity by leaving the lens epithelial cells and residual cortex exposed to the immunologically activated aqueous humor or failing to achieve the mechanical fixation to the ocular tissues. These postulates, however, are only based on the clinical observations in the separate two studies and remain highly speculative. Further studies are needed to elucidate this point as well as to seek ideal lens materials for small incision cataract surgery. REFERENCES I. Sanders DR, Spigelman A, Kraff C, et al. Quantitative assessment of postsurgical breakdown of the bloodaqueous barrier. Arch Ophthalmol 1983; 101: 131133 2. Ohnishi Y, Tanaka M. Effects of pilocarpine and paracentesis on occluding junctions between the nonpigmented ciliary epithelial cells. Exp Eye Res 1981; 32: 635-647 3. Kraff MC, Sanders DR. Planned extracapsular extraction versus phacoemulsification with IOL implantation: A comparison of concurrent series. Am IntraOcular Implant Soc J 1982; 8:38-41 4. Farley MK, Kratz RP, Johnson SH, Olson PF. Phacoemulsification. In: Stark WJ, Terry AC, Maumenee AE, eds, Anterior Segment Surgery; IOLs, Lasers, and Re360
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6.
7. 8.
9.
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II. 12. 13. 14.
IS.
16. 17. 18.
19.
20.
21.
22.
fractive Keratoplasty. Baltimore, Williams & Wilkins, 1987; 166-175 Hurite FG. The contraindications to phacoemulsification and summary of personal experience. Trans Am Acad Ophthalmol Otolaryngol 1974; 78:0P-14-0P17 Kelman CD. Phacoemulsification and aspiration: the Kelman technique of cataract removal. In: Duane TD, Jaeger EA, eds, Clinical Ophthalmology, vol 5. Philadelphia, JB Lippincott Co, 1989; chap 8A Stur M, Grabner G, Huber-Spitzy V, et al. Effect of timolol on aqueous humor protein concentration in the human eye. Arch Ophthalmol1986; 104:899-900 Oshika T, Mori M, Araie M. Une nouvelle approche de I' etude de la dynamique de l'humeur aqueuse par la mesure de l'intensite de l'effet. J Tyndall. Fr Ophtalmol 1990; 13: 471-480 Oshika T, Araie M. Time course of changes in aqueous protein concentration and flow rate after oral acetazolamide. Invest Ophthalmol Vis Sci 1990; 31 :527534 Sawa M, Tsurimaki Y, Tsuru T, Shimizu H. New quantitative method to determine protein concentration and cell number in aqueous in vivo. Jpn J Ophthalmol 1988; 32:132-142 Oshika T, Kato S, Funatsu H. Quantitative assessment of aqueous flare intensity in diabetes. Graefes Arch Clin Exp Ophthalmol 1989; 227:518-520 Oshika T, Nishi M, Mochizuki M, et al. Quantitative assessment of aqueous flare and cells in uveitis. Jpn J Ophthalmol1989; 33:279-287 Oshika T, Kato S, Sawa M, Masuda K. Aqueous flare intensity and age. Jpn J Ophthalmol1989; 33:237-242 Drews RC. Management of postoperative inflammation: Dexamethasone versus flurbiprofen, a quantitative study using the new flare cell meter. Ophthalmic Surg 1990; 21:560-562 Spaiton DJ, Shah SM. A comparative study of the laser flare cell meter and fluorophotometry in the assessment of the blood aqueous barrier in the pathological eye. ARVO Abstracts. Invest Ophthalmol Vis Sci 1991; 32(4):886 Oshika T, Kato S. Changes in aqueous flare and cells after mydriasis. Jpn J Ophthalmol1989; 33:271-278 Neupert JR, Lawrence C. Protein release during aqueous withdrawal in rabbits. Invest Ophthalmol 1970; 9:865-872 Raviola G. Effects of paracentesis on the bloodaqueous barrier: an electron microscope study on Macaca mulatta using horseradish peroxidase as a tracer. Invest Ophthalmol 1974; 13:828-858 Okisaka S. Effects of paracentesis on the bloodaqueous barrier: a light and electron microscopic study on cynomolgus monkey. Invest Ophthalmol1976; 15: 824-834 Bartels SP, Pederson JE, Gaasterland DE, Armaly MF. Sites of breakdown of the blood-aqueous barrier after paracentesis of the rhesus monkey eye. Invest Ophthalmol Vis Sci 1979; 18:1050-1060 Smelser GK, Pei YF. Cytological basis of protein leakage into the eye following paracentesis. An electron microscopic study. Invest Ophthalmol 1965; 4:249263 Pederson JE, MacLellan HM, Gaasterland DE. The rate of reflux fluid movement into the eye from Schlemm's canal during hypotony in the rhesus monkey. Invest Ophthalmol Vis Sci 1978; 17:377-381
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23. Kraff MC, Sanders DR, Peyman GA, et al. Slit-lamp fluorophotometry in intraocular lens patients. Ophthalmology 1980; 87:877-880 24. Sanders DR, Kraff MC , Lieberman HL, et al. Breakdown and reestablishment of blood-aqueous barrier with implant surgery. Arch Ophthalmol 1982; 100: 588-590 25. Liesegang TJ, Bourne WM , Brubaker RF. The effect of cataract surgery on the blood-aqueous barrier. Ophthalmology 1984; 91 :399-402 26. Kaiya T. Observation of blood-aqueous barrier function after posterior chambe r intraocular lens implantation . J Cataract Refract Surg 1990; 16:320-324 27. Shepherd JR. Induced astigmatism in small incision cataract surgery. J Cataract Refract Surg 1989; 15: 85-88
28. Neumann AC, McCarty GR, Sanders DR, Raanan MG. Small incisions to control astigmatism during cataract surgery. J Cataract Refract Surg 1989; 15:7884 29 . Sanders DR, Maghraby AE, Kraff MC, Berkeley RG. Advantages of small-incision surgery. In: Gills JP, Sanders DR, eds, Small-Incision Cataract Surgery; Foldable Lenses, One Stitch Surgery, Sutureless Surgery, Astigmatic Keratotomy . Thorofare, Slack Inc, 1990; 313 30. Lyle WA, Jin JC . Comparison of a 3- and 6-mm incision in combined phacoemulsification and trabeculectomy. Am J Ophthalmol1991; 111 :189-196 31. Oshika T, Masuda K. Quantitative assessment of inflammation after intraocular lens implantation. JPn J Clin Ophthalmol1989; 43:177-180
J CATARACT REFRACT SURG-VOL 18, JULY 1992
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,', ABSTRACT prospective study was conducted in 120 patients to ::~s~¢$s .;tiietiine course of changes in intraocular inflammation after , ':i tlt~eellt3raet: strrgeryprQcedures: planned extracapsular extraction :·'.wi~~pply{Pt~h.ylmethacrylate) , (PMMA) intraocular lens (IOL) im;':~p!~d9_n(Ummincis.iongr.oup), phacoemulsificationwithPMMA :... lgl} mip:~~:JI.'~3ti~n(7ml1l 'incisiongroup), and phacoemulsificatiQn ::~th :f~lda.l?l~siUcone single-pieceIO L i'mplantation (4 mm incision ?,~~p.)-: :~chga;~~pwascarefullymatched for patients' ophthaltno:·;l()gj~ }ill\d, systel'nicbackgrounds. Patients with hard nuclei were : ~cl1;tded~ The degree ofiilflammation was evaluated by quantitatipg ,:;·;~qu~~1:li\1are .in'te~sityand cell count with the ~er flare-cell 'meter. ~~·.m1Jl.t,';~~tJyp~~t()perilti\(eperiod; both aqueous flare intensity and · ~I :£ount :were ; highest, in the II mm incision group followed, in .:.~ecf~{lS~gorder,bythe7 mmand 4 mm incisiongroups. Significant :. b¢~e¢Ji-grl)up differences were observed at one, two, and seven ·, p,oslQperativ.ed"ysf()l'fiare andone day through one week for cells. : ~o,thpilrame~ersineachgroup decreased to a similar level one .lli,Qnth3fter s~rgery,but flare intensity in all groups remained sig~iIicaijtlyhjgher than that of age-matched normal controls up to six ~~iltltspostoperatively. . -.-".:., Ac: Qne~y~ar
..
.
".
L
•
•
•
' li~YWords~extr~capsular ' extraction, flare~cell meter, intraocular
! ~;::
' . . f; , ,
'. l~ns,phacoemulsification, poly(methyl methacrylate), :"' po~s,urgica:linflammation, silicone
It is known that surgical trauma to the eye induces blood-aqueous barrier breakdown, leading to augmented protein leakage and cellular reaction in the aqueous humor. Modern cataract surgery, even with advances in surgical techniques and instrumentation and the efficacy of postsurgical remedies, can also induce this breakdown. In 1983, Sanders et aU demonstrated that a large penetrating limbal incision exerted a great degree of postsurgical blood-aqueous barrier breakdown using anterior segment fluorophotom-
etry in experimental surgical models. A morphological study in monkey eyes has shown that repeated paracentesis caused more severe disruption of the blood-aqueous barrier than a single paracentesis, 2 indicating that recurring ocular hypotony would result in greater damage to the barrier. These findings suggest that smaller incision cataract surgery, associated with a lower chance of ocular hypotony, may provoke a smaller degree of blood-aqueous barrier breakdown, helping to retain the postsurgical physiological environment within the eye.
From the Department of Ophthalmology, Tokyo Kosei Nenkin Hospital, Tokyo, japan (Oshika) and Miyata Eye Hospital, Miyazaki, japan (Yoshimura, Miyata). Presented in part at the Symposium on Cataract, IOL and Refractive Surgery, Boston, April 1991. Reprint requests to Tetsuro Oshika, MD" Department ofOphthalmology, Tokyo Kosei Nenkin Hospital, 5-1 Tsukudo-cho, Shinjuku-ku, Tokyo 162, japan. 356
J CATARACT REFRACT SURG-VOL 18, JULY 1992
Clinical observations indicate that phacoemulsification causes less postsurgical intraocular inflammation than planned extracapsular cataract extraction. 3 •4 However, no quantitative studies of the postsurgical inflammation and/or bloodaqueous barrier breakdown in these two procedures have been done. Despite the increasing interest in small incision cataract surgery using phacoemulsification and foldable intraocular lenses (IOLs), we do not know whether this new technique is more advantageous than the conventional techniques in lessening the degree of postoperative inflammation or quickening the process of blood-aqueous barrier re-establishment. We undertook the current study to assess the time course of changes in intraocular inflammation after cataract surgery performed by three procedures in groups of patients whose ophthalmologic and systemic backgrounds were as similar as possible. SUBJECTS AND METHODS Healthy patients scheduled for cataract extraction with posterior chamber IOL implantation were enrolled in the study. To enable random assignment of the patients to extracapsular extraction or phacoemulsification, those with a very hard and brunescent cataract, which was considered to be a contraindication of phacoemulsification,5,6 were excluded prior to initiating the study. Those who had any preoperative pathology which would confound the results were also excluded. Surgeries were performed using one of the following three procedures: (1) extracapsular cataract extraction and poly(methyl methacrylate) (PMMA) posterior chamber IOL implantation (11 mm incision group); (2) phacoemulsification and PMMA posterior chamber IOL implantation (7 mm incision group); (3) phacoemulsification and silicone posterior chamber IOL implantation (4 mm incision group). In Groups 1 and 2 (extracapsular extraction or phacoemulsification with PMMA IOL), the study was carried out in a randomized-parallel design; in Group 3 (phacoemulsification with silicone IOL) it was conducted in a similar group of patients at a later period because of the availability of the lens. Surgeries were performed by the authors in two facilities, Tokyo Kosei Nenkin Hospital (T.O.) and Miyata Eye Hospital (K.Y. and N.M.), from February 1989 to January 1990 for the PMMA lens series and from March to July 1990 for the silicone lens series. Ninety eyes of 90 patients fulfilling the criteria for cataract surgery were selected for the first series (Groups A and B). They were randomly assigned to the extracapsular extraction or phaco-
emulsification groups; 45 patients were in each group. The average age was 70.5 ± 1.2 and 71.3 ± 1.1 (mean ± SE) years, respectively. Randomization was done using a serial list of random numbers. In the extracapsular extraction group, nuclei were extracted through an 11 mm limbal incision after capsulorhexis. Following removal of residual cortex with an automated irrigation/aspiration unit, a 6.5 mm optic three-piece PMMA IOL (unmodified surface) was inserted into the capsular bag. Sodium hyaluronate was used to facilitate lens insertion and was aspirated as completely as possible at the end of surgery. The limbal incision was closed with a shoelace suture using 10-0 nylon. No patient received a peripheral iridectomy. Phacoemulsification was performed with capsulorhexis and emulsification of the nuclei in the posterior chamber. An IOL similar to the one in the extracapsular extraction group was inserted through a 7 mm incision into the capsular bag. Except for the method of nuclei removal and incision size, the surgical techniques were the same as in the extracapsular extraction procedure. The latter series (Group C) included 30 eyes of an additional 30 patients (71.1 ± 1.0 years) having phacoemulsification and silicone single-piece IOL implantation. The same admission criteria as in the previous series was applied for the selection of patients, and no significant difference in patient age between the two series was found. Following capsulorhexis and in situ emulsification of the nuclei, the cortex was removed with an automated irrigation/aspiration unit. The IOL was inserted into the capsular bag through a 4 mm limbal incision using a silicone lens injector. The wound was closed with a single 10-0 horizontal suture. Other surgical techniques were similar to those used in the first series. Patients in each group received the same routine preoperative and postoperative medications. Preoperative pupillary dilation was accomplished using topical 5% phenylephrine, 0.5% tropicamide, and 0.5% indomethacin, each given three times with a 30 minute interval between applications. Postoperative medications included topical 0.1 % betamethasone and 0.3% ofloxacin three times a day for two to three months. An anti prostaglandin agent, i.e., 0.5% indomethacin, was also instilled twice daily for one week and once daily thereafter up to two months. No steroids were injected subconjunctivally at the end of or after surgery. Patients were excluded if they, because of preoperative or postoperative intraocular pressure elevation, were treated by topical or systemic ocular hypotensive agents, which are known to affect
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aqueous flare intensity (aqueous protein concentration).7-Y Flare intensity and cell count in the aqueous humor were measured with the laser flare-cell meter; this apparatus and sensitivity have been described elsewhere. 10 -I.5 Measurements were taken before surgery (baseline) and 1, 2, 3 days, 1,2 weeks, and 1, 3, 6, and 12 months after surgery. Each measurement was made 30 to 60 minutes after topical application of O.S% phenylephrine and O.S% tropicamide. 16 Fifteen normal volunteers (7l.0 ± l.S years) were recruited to serve as age-matched controls (30 eyes). They received topical mydriatics and were measured with the laser flare-cell meter 30 minutes after instillation.) 6 Obtained data for flare intensity and cell count were compared among groups by the Friedman rank test of variance to test the null hypothesis that there was no difference among procedures. Specific differences in mean values between groups were tested for significance with the Wilcoxon rank-sum test.
RESULTS One hundred twenty patients entered the study. One patient in the 11 mm incision group and one in the 4 mm incision group were excluded because of surgical complications. After surgery, four patients were treated with ocular hypotensive agents for raised intraocular pressure. According to the protocol, studies in these cases were discontinued and the data were discarded. During the one-year postoperative course of the study, a few patients missed some of the predetermined follow-up visits . Eleven patients, who failed to appear on more than three occasions of nine scheduled examination periods, were eventually excluded from our analysis. Data from the remaining 103 patients were collected and analyzed: 39 eyes in the 11 mm incision group (extracapsular extraction and PMMA lens), 38 in the 7 mm incision group (phacoemulsification and PMMA lens), and 26 in the 4 mm incision group (phacoemulsification and silicone lens). Figure 1 compares preoperative and postoperative flare intensity in each group. Preoperative flare values were 6.2 ± 0.4,6.0 ± 0.3, and 6.4 ± 0.3 (mean ± SE) photon count/msec for the 11 mm, 7 mm and 4 mm incision groups, respectively; these were comparable to those of the age-matched normal controls, 6.3 ± 0.2 photon count/msec. In the immediate postoperative period, the 11 mm incision group had the highest flare intensity, followed, in decreasing order, by the 7 mm and 4 mm incision groups. Significant differences among the 358
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(Oshika) Changes in aqueous flare intensity follOWing cataract surgery performed with different procedures: 11 mm-planned extracapsular extraction with PMMA lens implantation; 7 mm-phacoemulsification with PMMA lens implantation; 4 mmphacoemulsification with silicone single-piece lens implantation; control-age-matched normal controls .
three procedures were observed at one and two days and one week postoperatively (Table 1). Flare intensity in each group decreased to a similar level one month after surgery. However, values remained significantly higher than those of the normal controls until three months postoperatively (P < .01). At the 6 and 12 month postoperative examinations, this difference was not statistically apparent. Postoperative cell count exhibited a tendency similar to that ofthe flare measurements (Figure 2). There were significant between-group differences from the first postoperative day and these persisted through one week after surgery (Table 1). No significant differences were noted at the one month and later observation periods. . Following the initial high flare intensity and cell count immediately after surgery, both parameters declined steadily. But flare intensity in the 4 mm incision group (silicone lens) displayed a slight rebound at two weeks postoperatively, forming a small second peak which was significantly higher than the values at one week postoperatively (P < .OS). DISCUSSION The current study compared the degree of intraocular inflammation after three different procedures of cataract surgery. Because of different methods of nucleus removal and dissimilar IOL materials in each group, the data obtained may not directly reflect the influence of incision size and/or
J CATARACT REFRACT SURG-VOL 18, JULY 1992
Table 1. Statistical analysis of Hare intensity and cell count. Flare Intensity Time Period Preoperative
Variance
Cell Count
11 mm7 mm
11 mm4 mm
7mm4mm
Variance
11 mm7mm
11 mm4mm
7mm4mm
P < .001
P < .05
P < .001
P< .01
P < .001
N.S.
P < .001
N.S.
P< .01
P< .05
P < .001
P< .05
P< .01
P< .05
P< .01
P< .05
P< .01
P < .01
P< .01
N.S.
N.S.
N.S.
1 day
P < .001
P < .001
2 days
P< .01
P < .01
3 days
N.S.
1 week
P< .05
2 weeks
N.S.
N.S.
1 month
N.S.
N.S.
N.S.
P < .01
N.S.
2 months
N.S.
N.S.
3 months
N.S.
N.S.
6 months
N.S.
N.S.
12 months
N.S.
N.S.
N.S.: Not significant.
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Fig. 2.
(Oshika) Changes in cell count following cataract surgery performed with different procedures: 11 mm-planned extracapsular extraction with PMMA lens implantation; 7 mm-phacoemulsification with PMMA lens implantation; 4 mm-phacoemulsification with silicone single-piece lens implantation.
surgical techniques on postoperative inflammation. For a more precise and controlled assessment of these factors, studies using identical lens material and surgical techniques would be required. Nevertheless, we did not feel it practical to perform phacoemulsification with IOL implantation through an 11 mm incision or to insert a foldable lens through a 7 mm or greater incision. Moreover, the present study was conducted to evaluate three standard surgical procedures, involving their peculiar surgical techniques and lens materials as part of the procedures. Thus, the authors used their routine surgical techniques with only minor mod-
ifications to obtain possible congruence among groups. One special consideration in designing this study was that patients with a very hard nuclei contraindicated for phacoemulsification were excluded to match the ophthalmologic and systemic backgrounds of the patients in each group . Results of the present study demonstrated that immediate postoperative inflammation was significantly greater in the larger incision surgery groups. Statistically significant differences were observed at one, two, and seven postoperative days for flare intensity and one day through one week for cell count_ There are at least two possible explanations for this result: (I) The longer corn eoscleral wound provoked a greater degree of irritation to the uveal tissues, leading to a subsequent increase in the synthesis of inflammatory mediators. (2) The wider limbal opening induced a greater extent of ocular hypotony, which is known to result in a reflux of serum components via the trabecular meshwork into the anterior chamber 17 - 2o and/or disruption of the bloodaqueous barrieL2.19-22 This second postulate is plausible because extraction of the whole nuclei through a large limbal incision commonly leads to collapse and hypotony of the anterior chamber. Procedures using smaller incisions would better avoid intraoperative ocular hypotony by maintaining the configuration of the globe and allowing the least amount of fluid leakage through the wound. At the one month and later postoperative observation periods, no significant differences in either aqueous flare intensity or cell count among the three groups were found. This suggests that no
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clinically apparent difference in long-term influence on the blood-aqueous barrier function exists between the procedures. We were interested in the finding that flare intensity in all surgery groups remained at levels higher than those of age-matched normal controls and preoperative baseline measurements until six months postoperatively. This result, which agrees with previous fl uorophotometric studies,23-26 indicates that blood-aqueous barrier function is not completely re-established for a long period after surgery. Small incision cataract surgery using phacoemulsification and a foldable IOL has several clinically proven advantages over larger incision surgery, 27 -30 including reduction of induced astigmatism, better uncorrected visual acuity, earlier stabilization of refraction, and more rapid healing. In view of these findings and the present results, it appears that smaller incision surgery allows faster physical and visual rehabilitation. As shown in the results, flare intensity in the silicone lens group rebounded two weeks after surgery, although this change was not clinically significant. Our previous study using a hydrogel IOL revealed an identical phenomenon at the same postoperative period. 31 Silicone and hydrogel share the physical characteristics of high biocompatibility, which results in the lack of adhesion between the lens and surrounding ocular tissues. It might be that this feature of both soft materials had played a role in producing the rebound of flare intensity by leaving the lens epithelial cells and residual cortex exposed to the immunologically activated aqueous humor or failing to achieve the mechanical fixation to the ocular tissues. These postulates, however, are only based on the clinical observations in the separate two studies and remain highly speculative. Further studies are needed to elucidate this point as well as to seek ideal lens materials for small incision cataract surgery. REFERENCES I. Sanders DR, Spigelman A, Kraff C, et al. Quantitative assessment of postsurgical breakdown of the bloodaqueous barrier. Arch Ophthalmol 1983; 101: 131133 2. Ohnishi Y, Tanaka M. Effects of pilocarpine and paracentesis on occluding junctions between the nonpigmented ciliary epithelial cells. Exp Eye Res 1981; 32: 635-647 3. Kraff MC, Sanders DR. Planned extracapsular extraction versus phacoemulsification with IOL implantation: A comparison of concurrent series. Am IntraOcular Implant Soc J 1982; 8:38-41 4. Farley MK, Kratz RP, Johnson SH, Olson PF. Phacoemulsification. In: Stark WJ, Terry AC, Maumenee AE, eds, Anterior Segment Surgery; IOLs, Lasers, and Re360
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23. Kraff MC, Sanders DR, Peyman GA, et al. Slit-lamp fluorophotometry in intraocular lens patients. Ophthalmology 1980; 87:877-880 24. Sanders DR, Kraff MC , Lieberman HL, et al. Breakdown and reestablishment of blood-aqueous barrier with implant surgery. Arch Ophthalmol 1982; 100: 588-590 25. Liesegang TJ, Bourne WM , Brubaker RF. The effect of cataract surgery on the blood-aqueous barrier. Ophthalmology 1984; 91 :399-402 26. Kaiya T. Observation of blood-aqueous barrier function after posterior chambe r intraocular lens implantation . J Cataract Refract Surg 1990; 16:320-324 27. Shepherd JR. Induced astigmatism in small incision cataract surgery. J Cataract Refract Surg 1989; 15: 85-88
28. Neumann AC, McCarty GR, Sanders DR, Raanan MG. Small incisions to control astigmatism during cataract surgery. J Cataract Refract Surg 1989; 15:7884 29 . Sanders DR, Maghraby AE, Kraff MC, Berkeley RG. Advantages of small-incision surgery. In: Gills JP, Sanders DR, eds, Small-Incision Cataract Surgery; Foldable Lenses, One Stitch Surgery, Sutureless Surgery, Astigmatic Keratotomy . Thorofare, Slack Inc, 1990; 313 30. Lyle WA, Jin JC . Comparison of a 3- and 6-mm incision in combined phacoemulsification and trabeculectomy. Am J Ophthalmol1991; 111 :189-196 31. Oshika T, Masuda K. Quantitative assessment of inflammation after intraocular lens implantation. JPn J Clin Ophthalmol1989; 43:177-180
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