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Endothelial cell loss after cataract phacoemulsification with Healon5 vs. I-Visc Phaco
Endothelial cell loss after cataract phacoemulsification with HealonS vs. I-Vise Phaco George H.H. Beiko, BM, BCh, FRCSC ABSTRACT• RESUME Background: Healon5, the first viscoadaptive agent introduced in ophthalmic
surgery, has been judged to be superior to Healon GV in protecting corneal endothelial cells. The purpose of this study was to compare the endothelial pro tective effects of I-Vise Phaco, a newer viscoadaptive agent, with those of Healon5 in cataract phacoemulsification. Methods: A total of 96 unselected patients scheduled to undergo cataract surgery at a community-based hospital in St. Catharines, Ont., were assigned to receive I-Vise Phaco. This group was compared with I 12 patients who had received Healon5 in a previous study by the author. The technique used to remove the cataract with pha coemulsification and insertion of an intraocular lens was the same in the two groups. Endothelial cell count and corneal thickness were measured preoperative ly and 3 and 8 weeks postoperatively with a Konan noncontact specular micro scope. One-way analysis of variance was used to analyse the data. Results: Preoperatively there was no statistically significant difference between the Healon5 and I-Vise Phaco groups in age, eye operated, or endothelial cell count or corneal thickness. At 3 weeks there was no significant difference between the two groups in mean endothelial cell count (2110.2 [standard deviation (SD) 529.9] cells/mm 2 vs. 2113.5 [SD 566.6] cells/mm 2) or mean corneal thickness (586.2 µm [SD 46.73 µm] vs. 583.9 µm [SD 42.23 µm]). Similarly, there was no sig nificant difference between the two groups in mean endothelial cell count (21 13.3 [SD 496.6] cells/mm 2 vs. 2145.5 [SD 573.1] cells/mm 2) or mean corneal thickness (570.9 µm [SD 44.09 µm] vs. 574.4 µm [SD 40.73 µm]) at 8 weeks.
Interpretation: Results at 3 and 8 weeks postoperatively indicate that HealonS and I-Vise Phaco protect the endothelium equally well during cataract phacoemulsification surgery. Contexte: L'on a juge que Healon5, premier agent viscoadaptatif introduit en chirurgie
oculaire, etait superieur au Healon GV pour proteger les cellules endotheliales de la cornee. L'etude avait pour objet de comparer les effets protecteurs endotheliaux
Dr. Beiko is in private practice in St. Catharines, Ont., and is on staff at the H6tel-Dieu Health Sciences Hospital, St. Catharines.
Accepted for publication Nov. 22, 2002 Reprint requests to: Dr. George H.H. Beiko, 103-180 Vine St., St. Catharines ON L2R 7P3; fax (905) 687-8766; george.beiko@ sympatico.ca
Presented in part at the Canadian Society of Cataract and Refractive Surgery meeting held in Toronto in April 2002 and at the American Society of Cataract and Refractive Surgery meeting held in Philadelphia in June 2002
This article has been peer-reviewed.
Originally received July 23, 2002
Can j Ophthalmol 2003;38:52-6
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Endothelial cell loss-Beiko
Endothelial cell loss-Beiko d'l-Visc Phaco, viscoadaptatif plus recent, avec ceux de Healon5 lors de la phaco emulsification de la cataracte. Methodes : En tout, 96 patients non selectionnes, qui attendaient une chirurgie de la cataracte dans un h6pital local de St. Catharines (Ontario), ont ete retenus pour recevoir l'agent I-Vise Phaco. L'on a compare ce groupe avec 112 patients qui avaient re~u Healon5 lors d'une etude precedente de l'auteur. La technique utilisee pour enlever la cataracte a ete la meme pour les deux groupes : phacoemulsifica tion et insertion d'une lentille intraoculaire. Le compte des cellules endotheliales et l'epaisseur de la cornee ont ete mesures avant !'operation, puis 3 et 8 semaines apres la chirurgie, avec un microscope speculaire sans contact Konan. Une analyse de variance simple a ete appliquee a !'analyse des donnees. Resultats : Avant !'operation, ii n'y avait pas de difference importante sur le plan statistique entre les sujets ayant re~u le Healon5 et ceux qui devaient recevoir 1'1-Visc Phaco, concernant l'age, l'ceil opere, le compte des cellules endotheliales ou l'epaisseur de la cornee. A 3 semaines, ii n'y avait pas d'ecart significatif entre les deux groupes concernant le compte moyen des cellules endotheliales (21 I0,2 cel lules/mm2 [ecart type (ET) 529,9] c. 2113,5 cellules/mm 2 [ET 566,6]) ou l'epaisseur moyenne de la cornee (586,2 µm [ET 46,73 µm] c. 583,9 µm [ET 42,23 µm]). De meme, ii n'y avait pas de difference importante entre les deux groupes concernant le compte moyen des cellules endotheliales (2113,3 cellules/mm 2 [ET 496,6] c. 2145,5 cellules/mm 2 [ET 573, I]) ou l'epaisseur moyenne de la cornee (570,9 µm [ET 44,09 µm] c. 574,4 µm [ET 40,73 µm]), apres 8 semaines.
Interpretation : Les resultats obtenus apres 3 et 8 semaines indiquent que l'un et l'autre, HealonS et I-Vise Phaco, protegent bien !'endothelium pendant la chirurgie de la cataracte par phacoemulsification.
0
phthalmic viscosurgical devices are used in cat aract phacoemulsification surgery not only to facilitate the surgery but also to protect corneal endothelial cells. These cells function to maintain deturgescence of the corneal stroma, thus maintaining transparency. 1 The number of endothelial cells is known to decrease with aging. 2 Cataract surgery also causes loss of endothelial cells at the time of surgery. 3,4 Recent interest has focused on minimizing this loss. Until recently, ophthalmic viscosurgical devices were described as dispersive or cohesive, based on their zero shear rate (the limiting viscosity at which a viscoelastic becomes stationary). Dispersive agents have a zero shear viscosity of 1000 to 100 000 mP, and cohesive agents have a zero shear viscosity of 100 000 to 5 million mP. In 1998 a new class of oph thalmic viscosurgical devices, the viscoadaptive agents, was introduced. Viscoadaptive agents have a zero shear viscosity of 7 million to 24 million mP. Dispersive agents function as dispersives throughout the range of fluid turbulence at normal flow rates dur ing cataract phacoemulsification (10 to 35 mL/min); cohesive agents show cohesive behaviour throughout this same range. Viscoadaptives are unique in that they behave like supercohesive agents at low flow rates and
like dispersive agents by fracturing at rates above 25 mL/min. 5 Healon5 (Pharmacia Canada Inc., Mississauga, Ont.) was the first viscoadaptive agent introduced for ophthalmic surgery. It has been judged to have excel lent handling characteristics during all phases of cataract phacoemulsification. 6 In addition, it has been found to be superior to Healon GV, the previous gold standard, in protecting endothelial cells. 7 Recently, a second viscoadaptive agent, I-Vise Phaco (I-Med Pharma Inc., Montreal), was introduced. The aim of this study was to compare the endothelial pro tective properties of this agent with those of Healon5. METHODS
A comparative study was carried out among patients scheduled to undergo cataract surgery at a community based hospital in St. Catharines, Ont. The patients were candidates for small-incision cataract phacoemulsifica tion with implantation of a foldable intraocular lens. If both eyes of one patient were included in the study, no attempt was made to use the patient as his or her own control subject. The exclusion criteria were previous ocular surgery, low preoperative endothelial cell count
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Endothelial cell loss-Beiko
(less than 900 cells/mm2), central corneal dystrophy or degeneration, and inability to complete the study. Institutional review board/ethics committee approval was not required for the study. The two viscoadaptive agents used were Healon5 (2.3% sodium hyaluronate) and I-Vise Phaco (2.5% sodium hyaluronate). Randomization was achieved by masking the booking clerk as to which viscoadaptive agent would be used, and the surgeon as to the clini cal details of the patients when a choice of viscoadap tive agent to be used on a given day was made. No attempt was made to mask the viscosurgical device, as each has its own distinctive delivery system. Target sample sizes were calculated with the use of results of a previous study in which 32 patients were randomly assigned to receive either Healon GV or Duo Vise (Alcon Canada Inc., Mississauga). 8 Although statistical significance between study groups was not achieved in the previous study, the values for endothe lial cell loss and standard deviation were used to deter mine the sample size for the current study. Assuming endothelial cell loss of 9%, with a standard deviation of 12%, a difference of at least 3% between the study groups and the mean, a power of 80% and a signifi cance level of p = 0.05, at least 62 patients had to be enrolled in either arm of the study. With a nonparamet ric adjustment, 75 patients per arm would be required. A total of 96 consecutive patients received I-Vise Phaco during surgery performed between June and August 2001. This group was compared to 112 patients who received Healon5 during their surgery, done between October 2000 and January 2001. 9 All surgical procedures were performed by the same surgeon (G.H.H.B.) using the same standard technique for cataract phacoemulsification. Preoperatively, eye drops, including diclofenac (Voltaren Ophtha, CIBA Vision Canada Inc., Mississauga), 0.3% ciprofloxacin (Ciloxan, Alcon Canada Inc.), 1%cyclopentolate,2.5% phenylephrine and 0.5% bupivacaine (Marcaine, Abbott Laboratories Limited, Saint-Laurent, Que.), were instilled. The surgery was performed under topi cal anesthesia, with some neuroleptic assistance (the anesthesiologist decided which neuroleptic agent was used). An oblique limbal incision was made at the 10 o'clock position with a diamond keratome; in patients with corneal astigmatism greater than 1.00 dioptre, the incision was made on the steep axis of the astigmatism. The viscoadaptive agent was then instilled into the anterior chamber. Capsulorrhexis was performed, and hydrodissection with 1.0% unpreserved lidocaine (AstraZeneca Canada Inc., Mississauga) was done. The cataract was removed by means of phacoemulsifica
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tion, and the cortical remnants were removed using aspiration in the irrigation-aspiration mode. The Surgical Design Ocusystem ART phacoemulsification unit (Surgical Design Corp., Long Island City, NY) was used for phacoemulsification and aspiration. A low-flow (20 mL/min), low-vacuum (40 mm Hg) tech nique was used for sculpting and nucleus removal; the power was linear. Phacoemulsification was performed at the iris plane, with the bevel of the needle pointed down. The irrigation fluid used was balanced salt solu tion (BSS) with added epinephrine (0.3 mL of 1: 1000 solution per 500 mL), gentamicin (4 mg/500 mL) and vancomycin (10 mg/500 mL). The viscoadaptive agent was then used to fill the capsular bag and anterior chamber. A foldable lens was implanted in the capsular bag, and the viscoadaptive agent was removed. Removal of the viscoadaptive agent was the same in all patients. The irrigation-aspiration tip was placed posterior to the lens, and the agent was first removed from this position. The tip was then placed on the anterior surface of the lens, and the viscoadaptive agent was aspirated from this position. Aspiration was performed with a flow rate of 30 mL/min, a vacuum of 350 mm Hg and a bottle height of 70 cm above the patient's eye level. After aspiration, a syringe filled with the modified BSS was used to flush the anterior chamber angles and the endothelial surface for any remaining viscoadaptive agent; in most cases 3 mL to 5 mL was used. The anterior chamber was then re filled with the modified BSS. The incision was left unsutured. After 0.5% carba chol drops, gentamicin and 5% povidine-iodine drops were instilled on the eye, an eye shield was placed. On the first postoperative day the patient was in structed to use 0.5% ketorolac tromethamine (Acular, Allergan, Inc., Markham, Ont.) or diclofenac (Voltaren Ophtha) and 0.1 % dexamethasone-0.3% tobramycin (Tobradex, Alcon Canada Inc.) eye drops four times daily (the choice of anti-inflammatory depended on the time of entry into the study, as a change in the routine postoperative anti-inflammatory was made during the course of the study). This regimen was recommended for 3 weeks, after which time the patient was advised to use Tobradex twice daily for a further 4 weeks. Pachymetry and specular microscopy were per formed with a noncontact specular microscope (Konan Noncon Robo Pachy, model SP-9000, Konan Medical Corporation, Fairlawn, NJ). Central readings were obtained before surgery and 3 and 8 weeks after surgery. At least two readings were obtained at each visit; if there was a discrepancy of greater than 10% between the readings, further readings were taken
Endothelial cell loss-Beiko
Table I-Characteristics of patients undergo ing cataract phacoemulsification surgery with either HealonS or I-Vise Phaco Characteristic Mean age (and standard deviation [SD]), yr Right eye,% Mean endothelial cell count (and SD) per mm 2 Mean corneal thickness (and SD), µm
Healon5 (n= 112)
I-Vise Phaco (n =96)
74.5 (9.71) 47.3
75.7 (7.76) 44.8
2418.3 (446.4)
2438.7 (433.2)
581.2 (45.34)
584.4 (42.09)
until two readings within 10% of each other were obtained. The average of the two readings was record ed for analysis. Patients who missed one follow-up appointment were included in the study; patients who missed both follow-up appointments were excluded. One-way analysis of variance was used to analyse the data. RESULTS
There was no statistically significant difference between the two groups in number, age, eye operated, or preoperative endothelial cell count or corneal thick ness (Table 1). Table 2 shows the mean endothelial cell count and corneal thickness at 3 and 8 weeks postoperatively. At 3 weeks the endothelial cell count was decreased in both treatment groups compared to preoperative lev els; however, there was no statistically significant dif ference between the two groups (p = 0.967). Corneal thickness had returned to preoperative levels in both groups; there was no significant difference between the two groups (p =0.715). The mean endothelial cell count and corneal thickness at 8 weeks were not sig nificantly different from those at 3 weeks. Again, there was no significant difference between the two groups (p = 0.676 for endothelial cell count and p = 0.572 for corneal thickness). INTERPRETATION
Both Healon5 and I-Vise Phaco are highly retentive in cataract surgery. In both groups it was routinely
Table 2-Mean endothelial cell count and corneal thickness 3 and 8 weeks postopera tively in the two groups Group; mean (and SD) Variable Endothelial cell count (and SD) per mm 2 3 wk 8wk Corneal thickness (and SD), µm 3 wk 8 wk *n tn
Healon5*
I-Vise Phacot
2110.2 (529.9) 21 13.3 (496.6)
2113.5 (566.6) 2145.5 (573.1)
586.2 (46.73) 570.9 (44.09)
583.9 (42.23) 574.4 (40.73)
= I06 at 3 weeks and I02 at 8 weeks. = 89 at 3 weeks and 91 at 8 weeks.
evident that the viscosurgical device was present within the anterior chamber following phacoemulsifi cation. Retention of the viscosurgical device protects the endothelium from particulate matter, free radicals formed during phacoemulsification and air bubbles, thus reducing endothelial cell loss. In this study the endothelial protective properties of Healon5 and I-Vise Phaco were comparable. The han dling properties of the two agents were similar throughout all phases of cataract phacoemulsification. Pachymetry readings typically are increased on the first day following phacoemulsification and return to preoperative levels by 2 weeks to 2 months postopera tively.10·11 It has been reported that on the first postop erative day, corneal thickness is increased with Healan GV and with I-Vise Phaco but not with Healon5. 12 In the current study corneal thickness was not measured on the first postoperative day but had returned to pre operative levels by 3 weeks in both groups. Measurements of endothelial cell counts are highly reproducible when done with a specific specular microscope, but the results are not interchangeable between different types of specular microscope. 13 Thus, to critically evaluate the findings of the current study, it would be necessary to review previous stud ies done with a noncontact Konan specular micro scope. Although the Konan specular microscope has been used to study endothelial cell loss, 14 no pub lished data for Healon5 or I-Vise Phaco with this device could be found. Studies of endothelial cell loss with Healon5 in which other specular microscopes were used have
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Endothelial cell loss-Beiko been published. 15 •16 These studies showed significant ly better protection with Healon5 than with other cohesive or dispersive viscosurgical devices. In the current study endothelial cell loss had stabi lized by 3 weeks postoperatively. This finding is in con trast to a report from the Oxford Cataract Treatment and Evaluation Team, 17 who recommended that the read ings be done at least 90 days postoperatively. However, this conclusion was based on cataract extraction using both intracapsular and extracapsular techniques. In the current study, phacoemulsification was per formed using a low-flow, low-vacuum technique. This was done to ensure that the optimum environ ment was created for maintaining the viscoadaptive agent in the anterior chamber. Increasing the flow rate and vacuum results in greater turbulence in the ante rior chamber and loss of the viscoadaptive agent. The standard deviation of the endothelial cell count in the current study was as large as the change in endothelial cell count. This is a common observation in measurements of endothelial cell count. 18 •19 How ever, the analysis of variance technique compensates for this phenomenon. Thus, the p value gives a true indication of the validity of the findings. In conclusion, Healon5 and I-Vise Phaco function similarly in facilitating cataract phacoemulsification and protecting corneal endothelial cells. This study was supported by a grant from I-Med Pharma Inc. The author has no financial or proprietary interest in any of the products mentioned in this paper. REFERENCES
1. Khodadoust AA, Green K. Physiological function of regenerating endothelium. Invest Ophthalmol Vis Sci 1976;15:96-101. 2. Nishida T. Basic science: cornea, sclera, and ocular adnexa anatomy, biochemistry, physiology, and biome chanics. In: Krachmer JH, Mannis MJ, Holland E, editors. Cornea. Vol 1. St Louis: Mosby; 1977. p. 1-40. 3. Matsuda M, Suda T, Manabe R. Serial alterations in endothelial cell shape and pattern after intraocular sur gery. Am J Ophthalmol 1984;98:313-9. 4. Schultz RO, Glasser DB, Matsuda M, Yee RW, Edelhauser HF. Response of the corneal endothelium to cataract surgery. Arch Ophthalmol 1986;104:1164-9. 5. Arshinoff SA. Why Healon5? The meaning of "viscoad aptive." Ophthalmic Pract 1999; 17(6):332-4. 6. Arshinoff SA. Healon5. In: Buratto L, Giardini P, Bellucci R, editors. Viscoelastics in ophthalmic surgery. Thorofare (NJ): Slack Inc; 2000. p. 393-400.
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7. Beiko G. Prospective study of endothelial cell loss and pachymetry following cataract surgery, using Healon GV, Amvisc Plus and Healon5. American Society of Cataract and Refractive Surgery meeting; 2001 Apr; San Diego. 8. Beiko G. Prospective study of Healon GV and Duo Vise, and endothelial cell loss and pachymetry following cata ract surgery. American Society of Cataract and Refractive Surgery meeting; 2000 May; Boston. 9. Beiko G. Prospective study of endothelial cell loss in cataract phacoemulsification, comparing Healon5 and Vis coat. American Academy of Ophthalmology meeting; 2001 Nov; New Orleans. 10. Ventura AC, Awalti R, Bohnke M. Corneal thickness and endothelial density before and after cataract surgery. Br J Ophthalmol 2001 ;85(1):18-20. 11. Amon M, Menapace R, Scheidel W. Results of corneal pachymetry after small-incision hydrogel lens implanta tion and scleral-step incision poly(methyl methacrylate) lens implantation following phacoemulsification. J Cataract Refract Surg 1991;17(4):466-70. 12. Beiko G. Prospective study of pachmetry on the first post operative day after cataract phacoemulsification, using Healon GV, Healon5 and I-Vise Phaco. European Society of Cataract and Refractive Surgery meeting; 2001 Sept; Amsterdam. 13. Landesz M, Siertsema JV, Van Rij G. Comparative study of three semiautomated specular microscopes. J Cataract Refract Surg 1995;21(4):409-16. 14. Ravalico G, Tognetto D, Baccara F, Lovisato A. Corneal endothelial protection by different viscoelastics during phacoemulsification. J Cataract Refract Surg 1997;23(3): 433-9. 15. Schwenn 0, Dick HB, Krummenauer F, Christmann S, Vogel A, Pfeiffer N. Healon5 versus Viscoat during cat aract surgery: intraocular pressure, laser flare and corneal changes. Graefes Arch Clin Exp Ophthalmol 2000; 238(10):861-7. 16. Holzer MP, Tetz MR, Auffarth GU, Welt R, Volcker HE. Effect of Healon5 and 4 other viscoelastic substances on intraocular pressure and endothelium after cataract surgery. J Cataract Refract Surg 2001;27:213-8. 17. Oxford Cataract Treatment and Evaluation Team. Long term corneal endothelial cell loss after cataract surgery; results of a randomized controlled trial. Arch Ophthalmol 1986; 104: 1170-5. 18. Ravalico G, Tognetto D, Palomba MA, Lovisato A, Baccara F. Corneal endothelial function after extracapsu lar cataract extraction and phacoemulsification. J Cataract Refract Surg 1997;23(7): 1000-5. 19. Lee JH, Oh SY. Corneal endothelial cell loss from suture fixation of a posterior chamber intraocular lens. J Cataract Refract Surg 1997;23(7): 1020-2. Key words: phacoemulsification, ophthalmic viscosurgical devices, endothelial cell count, corneal thickness
surgery, has been judged to be superior to Healon GV in protecting corneal endothelial cells. The purpose of this study was to compare the endothelial pro tective effects of I-Vise Phaco, a newer viscoadaptive agent, with those of Healon5 in cataract phacoemulsification. Methods: A total of 96 unselected patients scheduled to undergo cataract surgery at a community-based hospital in St. Catharines, Ont., were assigned to receive I-Vise Phaco. This group was compared with I 12 patients who had received Healon5 in a previous study by the author. The technique used to remove the cataract with pha coemulsification and insertion of an intraocular lens was the same in the two groups. Endothelial cell count and corneal thickness were measured preoperative ly and 3 and 8 weeks postoperatively with a Konan noncontact specular micro scope. One-way analysis of variance was used to analyse the data. Results: Preoperatively there was no statistically significant difference between the Healon5 and I-Vise Phaco groups in age, eye operated, or endothelial cell count or corneal thickness. At 3 weeks there was no significant difference between the two groups in mean endothelial cell count (2110.2 [standard deviation (SD) 529.9] cells/mm 2 vs. 2113.5 [SD 566.6] cells/mm 2) or mean corneal thickness (586.2 µm [SD 46.73 µm] vs. 583.9 µm [SD 42.23 µm]). Similarly, there was no sig nificant difference between the two groups in mean endothelial cell count (21 13.3 [SD 496.6] cells/mm 2 vs. 2145.5 [SD 573.1] cells/mm 2) or mean corneal thickness (570.9 µm [SD 44.09 µm] vs. 574.4 µm [SD 40.73 µm]) at 8 weeks.
Interpretation: Results at 3 and 8 weeks postoperatively indicate that HealonS and I-Vise Phaco protect the endothelium equally well during cataract phacoemulsification surgery. Contexte: L'on a juge que Healon5, premier agent viscoadaptatif introduit en chirurgie
oculaire, etait superieur au Healon GV pour proteger les cellules endotheliales de la cornee. L'etude avait pour objet de comparer les effets protecteurs endotheliaux
Dr. Beiko is in private practice in St. Catharines, Ont., and is on staff at the H6tel-Dieu Health Sciences Hospital, St. Catharines.
Accepted for publication Nov. 22, 2002 Reprint requests to: Dr. George H.H. Beiko, 103-180 Vine St., St. Catharines ON L2R 7P3; fax (905) 687-8766; george.beiko@ sympatico.ca
Presented in part at the Canadian Society of Cataract and Refractive Surgery meeting held in Toronto in April 2002 and at the American Society of Cataract and Refractive Surgery meeting held in Philadelphia in June 2002
This article has been peer-reviewed.
Originally received July 23, 2002
Can j Ophthalmol 2003;38:52-6
52
Endothelial cell loss-Beiko
Endothelial cell loss-Beiko d'l-Visc Phaco, viscoadaptatif plus recent, avec ceux de Healon5 lors de la phaco emulsification de la cataracte. Methodes : En tout, 96 patients non selectionnes, qui attendaient une chirurgie de la cataracte dans un h6pital local de St. Catharines (Ontario), ont ete retenus pour recevoir l'agent I-Vise Phaco. L'on a compare ce groupe avec 112 patients qui avaient re~u Healon5 lors d'une etude precedente de l'auteur. La technique utilisee pour enlever la cataracte a ete la meme pour les deux groupes : phacoemulsifica tion et insertion d'une lentille intraoculaire. Le compte des cellules endotheliales et l'epaisseur de la cornee ont ete mesures avant !'operation, puis 3 et 8 semaines apres la chirurgie, avec un microscope speculaire sans contact Konan. Une analyse de variance simple a ete appliquee a !'analyse des donnees. Resultats : Avant !'operation, ii n'y avait pas de difference importante sur le plan statistique entre les sujets ayant re~u le Healon5 et ceux qui devaient recevoir 1'1-Visc Phaco, concernant l'age, l'ceil opere, le compte des cellules endotheliales ou l'epaisseur de la cornee. A 3 semaines, ii n'y avait pas d'ecart significatif entre les deux groupes concernant le compte moyen des cellules endotheliales (21 I0,2 cel lules/mm2 [ecart type (ET) 529,9] c. 2113,5 cellules/mm 2 [ET 566,6]) ou l'epaisseur moyenne de la cornee (586,2 µm [ET 46,73 µm] c. 583,9 µm [ET 42,23 µm]). De meme, ii n'y avait pas de difference importante entre les deux groupes concernant le compte moyen des cellules endotheliales (2113,3 cellules/mm 2 [ET 496,6] c. 2145,5 cellules/mm 2 [ET 573, I]) ou l'epaisseur moyenne de la cornee (570,9 µm [ET 44,09 µm] c. 574,4 µm [ET 40,73 µm]), apres 8 semaines.
Interpretation : Les resultats obtenus apres 3 et 8 semaines indiquent que l'un et l'autre, HealonS et I-Vise Phaco, protegent bien !'endothelium pendant la chirurgie de la cataracte par phacoemulsification.
0
phthalmic viscosurgical devices are used in cat aract phacoemulsification surgery not only to facilitate the surgery but also to protect corneal endothelial cells. These cells function to maintain deturgescence of the corneal stroma, thus maintaining transparency. 1 The number of endothelial cells is known to decrease with aging. 2 Cataract surgery also causes loss of endothelial cells at the time of surgery. 3,4 Recent interest has focused on minimizing this loss. Until recently, ophthalmic viscosurgical devices were described as dispersive or cohesive, based on their zero shear rate (the limiting viscosity at which a viscoelastic becomes stationary). Dispersive agents have a zero shear viscosity of 1000 to 100 000 mP, and cohesive agents have a zero shear viscosity of 100 000 to 5 million mP. In 1998 a new class of oph thalmic viscosurgical devices, the viscoadaptive agents, was introduced. Viscoadaptive agents have a zero shear viscosity of 7 million to 24 million mP. Dispersive agents function as dispersives throughout the range of fluid turbulence at normal flow rates dur ing cataract phacoemulsification (10 to 35 mL/min); cohesive agents show cohesive behaviour throughout this same range. Viscoadaptives are unique in that they behave like supercohesive agents at low flow rates and
like dispersive agents by fracturing at rates above 25 mL/min. 5 Healon5 (Pharmacia Canada Inc., Mississauga, Ont.) was the first viscoadaptive agent introduced for ophthalmic surgery. It has been judged to have excel lent handling characteristics during all phases of cataract phacoemulsification. 6 In addition, it has been found to be superior to Healon GV, the previous gold standard, in protecting endothelial cells. 7 Recently, a second viscoadaptive agent, I-Vise Phaco (I-Med Pharma Inc., Montreal), was introduced. The aim of this study was to compare the endothelial pro tective properties of this agent with those of Healon5. METHODS
A comparative study was carried out among patients scheduled to undergo cataract surgery at a community based hospital in St. Catharines, Ont. The patients were candidates for small-incision cataract phacoemulsifica tion with implantation of a foldable intraocular lens. If both eyes of one patient were included in the study, no attempt was made to use the patient as his or her own control subject. The exclusion criteria were previous ocular surgery, low preoperative endothelial cell count
CAN J OPHTHALMOL-VOL. 38, NO. I. 2003
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Endothelial cell loss-Beiko
(less than 900 cells/mm2), central corneal dystrophy or degeneration, and inability to complete the study. Institutional review board/ethics committee approval was not required for the study. The two viscoadaptive agents used were Healon5 (2.3% sodium hyaluronate) and I-Vise Phaco (2.5% sodium hyaluronate). Randomization was achieved by masking the booking clerk as to which viscoadaptive agent would be used, and the surgeon as to the clini cal details of the patients when a choice of viscoadap tive agent to be used on a given day was made. No attempt was made to mask the viscosurgical device, as each has its own distinctive delivery system. Target sample sizes were calculated with the use of results of a previous study in which 32 patients were randomly assigned to receive either Healon GV or Duo Vise (Alcon Canada Inc., Mississauga). 8 Although statistical significance between study groups was not achieved in the previous study, the values for endothe lial cell loss and standard deviation were used to deter mine the sample size for the current study. Assuming endothelial cell loss of 9%, with a standard deviation of 12%, a difference of at least 3% between the study groups and the mean, a power of 80% and a signifi cance level of p = 0.05, at least 62 patients had to be enrolled in either arm of the study. With a nonparamet ric adjustment, 75 patients per arm would be required. A total of 96 consecutive patients received I-Vise Phaco during surgery performed between June and August 2001. This group was compared to 112 patients who received Healon5 during their surgery, done between October 2000 and January 2001. 9 All surgical procedures were performed by the same surgeon (G.H.H.B.) using the same standard technique for cataract phacoemulsification. Preoperatively, eye drops, including diclofenac (Voltaren Ophtha, CIBA Vision Canada Inc., Mississauga), 0.3% ciprofloxacin (Ciloxan, Alcon Canada Inc.), 1%cyclopentolate,2.5% phenylephrine and 0.5% bupivacaine (Marcaine, Abbott Laboratories Limited, Saint-Laurent, Que.), were instilled. The surgery was performed under topi cal anesthesia, with some neuroleptic assistance (the anesthesiologist decided which neuroleptic agent was used). An oblique limbal incision was made at the 10 o'clock position with a diamond keratome; in patients with corneal astigmatism greater than 1.00 dioptre, the incision was made on the steep axis of the astigmatism. The viscoadaptive agent was then instilled into the anterior chamber. Capsulorrhexis was performed, and hydrodissection with 1.0% unpreserved lidocaine (AstraZeneca Canada Inc., Mississauga) was done. The cataract was removed by means of phacoemulsifica
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tion, and the cortical remnants were removed using aspiration in the irrigation-aspiration mode. The Surgical Design Ocusystem ART phacoemulsification unit (Surgical Design Corp., Long Island City, NY) was used for phacoemulsification and aspiration. A low-flow (20 mL/min), low-vacuum (40 mm Hg) tech nique was used for sculpting and nucleus removal; the power was linear. Phacoemulsification was performed at the iris plane, with the bevel of the needle pointed down. The irrigation fluid used was balanced salt solu tion (BSS) with added epinephrine (0.3 mL of 1: 1000 solution per 500 mL), gentamicin (4 mg/500 mL) and vancomycin (10 mg/500 mL). The viscoadaptive agent was then used to fill the capsular bag and anterior chamber. A foldable lens was implanted in the capsular bag, and the viscoadaptive agent was removed. Removal of the viscoadaptive agent was the same in all patients. The irrigation-aspiration tip was placed posterior to the lens, and the agent was first removed from this position. The tip was then placed on the anterior surface of the lens, and the viscoadaptive agent was aspirated from this position. Aspiration was performed with a flow rate of 30 mL/min, a vacuum of 350 mm Hg and a bottle height of 70 cm above the patient's eye level. After aspiration, a syringe filled with the modified BSS was used to flush the anterior chamber angles and the endothelial surface for any remaining viscoadaptive agent; in most cases 3 mL to 5 mL was used. The anterior chamber was then re filled with the modified BSS. The incision was left unsutured. After 0.5% carba chol drops, gentamicin and 5% povidine-iodine drops were instilled on the eye, an eye shield was placed. On the first postoperative day the patient was in structed to use 0.5% ketorolac tromethamine (Acular, Allergan, Inc., Markham, Ont.) or diclofenac (Voltaren Ophtha) and 0.1 % dexamethasone-0.3% tobramycin (Tobradex, Alcon Canada Inc.) eye drops four times daily (the choice of anti-inflammatory depended on the time of entry into the study, as a change in the routine postoperative anti-inflammatory was made during the course of the study). This regimen was recommended for 3 weeks, after which time the patient was advised to use Tobradex twice daily for a further 4 weeks. Pachymetry and specular microscopy were per formed with a noncontact specular microscope (Konan Noncon Robo Pachy, model SP-9000, Konan Medical Corporation, Fairlawn, NJ). Central readings were obtained before surgery and 3 and 8 weeks after surgery. At least two readings were obtained at each visit; if there was a discrepancy of greater than 10% between the readings, further readings were taken
Endothelial cell loss-Beiko
Table I-Characteristics of patients undergo ing cataract phacoemulsification surgery with either HealonS or I-Vise Phaco Characteristic Mean age (and standard deviation [SD]), yr Right eye,% Mean endothelial cell count (and SD) per mm 2 Mean corneal thickness (and SD), µm
Healon5 (n= 112)
I-Vise Phaco (n =96)
74.5 (9.71) 47.3
75.7 (7.76) 44.8
2418.3 (446.4)
2438.7 (433.2)
581.2 (45.34)
584.4 (42.09)
until two readings within 10% of each other were obtained. The average of the two readings was record ed for analysis. Patients who missed one follow-up appointment were included in the study; patients who missed both follow-up appointments were excluded. One-way analysis of variance was used to analyse the data. RESULTS
There was no statistically significant difference between the two groups in number, age, eye operated, or preoperative endothelial cell count or corneal thick ness (Table 1). Table 2 shows the mean endothelial cell count and corneal thickness at 3 and 8 weeks postoperatively. At 3 weeks the endothelial cell count was decreased in both treatment groups compared to preoperative lev els; however, there was no statistically significant dif ference between the two groups (p = 0.967). Corneal thickness had returned to preoperative levels in both groups; there was no significant difference between the two groups (p =0.715). The mean endothelial cell count and corneal thickness at 8 weeks were not sig nificantly different from those at 3 weeks. Again, there was no significant difference between the two groups (p = 0.676 for endothelial cell count and p = 0.572 for corneal thickness). INTERPRETATION
Both Healon5 and I-Vise Phaco are highly retentive in cataract surgery. In both groups it was routinely
Table 2-Mean endothelial cell count and corneal thickness 3 and 8 weeks postopera tively in the two groups Group; mean (and SD) Variable Endothelial cell count (and SD) per mm 2 3 wk 8wk Corneal thickness (and SD), µm 3 wk 8 wk *n tn
Healon5*
I-Vise Phacot
2110.2 (529.9) 21 13.3 (496.6)
2113.5 (566.6) 2145.5 (573.1)
586.2 (46.73) 570.9 (44.09)
583.9 (42.23) 574.4 (40.73)
= I06 at 3 weeks and I02 at 8 weeks. = 89 at 3 weeks and 91 at 8 weeks.
evident that the viscosurgical device was present within the anterior chamber following phacoemulsifi cation. Retention of the viscosurgical device protects the endothelium from particulate matter, free radicals formed during phacoemulsification and air bubbles, thus reducing endothelial cell loss. In this study the endothelial protective properties of Healon5 and I-Vise Phaco were comparable. The han dling properties of the two agents were similar throughout all phases of cataract phacoemulsification. Pachymetry readings typically are increased on the first day following phacoemulsification and return to preoperative levels by 2 weeks to 2 months postopera tively.10·11 It has been reported that on the first postop erative day, corneal thickness is increased with Healan GV and with I-Vise Phaco but not with Healon5. 12 In the current study corneal thickness was not measured on the first postoperative day but had returned to pre operative levels by 3 weeks in both groups. Measurements of endothelial cell counts are highly reproducible when done with a specific specular microscope, but the results are not interchangeable between different types of specular microscope. 13 Thus, to critically evaluate the findings of the current study, it would be necessary to review previous stud ies done with a noncontact Konan specular micro scope. Although the Konan specular microscope has been used to study endothelial cell loss, 14 no pub lished data for Healon5 or I-Vise Phaco with this device could be found. Studies of endothelial cell loss with Healon5 in which other specular microscopes were used have
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Endothelial cell loss-Beiko been published. 15 •16 These studies showed significant ly better protection with Healon5 than with other cohesive or dispersive viscosurgical devices. In the current study endothelial cell loss had stabi lized by 3 weeks postoperatively. This finding is in con trast to a report from the Oxford Cataract Treatment and Evaluation Team, 17 who recommended that the read ings be done at least 90 days postoperatively. However, this conclusion was based on cataract extraction using both intracapsular and extracapsular techniques. In the current study, phacoemulsification was per formed using a low-flow, low-vacuum technique. This was done to ensure that the optimum environ ment was created for maintaining the viscoadaptive agent in the anterior chamber. Increasing the flow rate and vacuum results in greater turbulence in the ante rior chamber and loss of the viscoadaptive agent. The standard deviation of the endothelial cell count in the current study was as large as the change in endothelial cell count. This is a common observation in measurements of endothelial cell count. 18 •19 How ever, the analysis of variance technique compensates for this phenomenon. Thus, the p value gives a true indication of the validity of the findings. In conclusion, Healon5 and I-Vise Phaco function similarly in facilitating cataract phacoemulsification and protecting corneal endothelial cells. This study was supported by a grant from I-Med Pharma Inc. The author has no financial or proprietary interest in any of the products mentioned in this paper. REFERENCES
1. Khodadoust AA, Green K. Physiological function of regenerating endothelium. Invest Ophthalmol Vis Sci 1976;15:96-101. 2. Nishida T. Basic science: cornea, sclera, and ocular adnexa anatomy, biochemistry, physiology, and biome chanics. In: Krachmer JH, Mannis MJ, Holland E, editors. Cornea. Vol 1. St Louis: Mosby; 1977. p. 1-40. 3. Matsuda M, Suda T, Manabe R. Serial alterations in endothelial cell shape and pattern after intraocular sur gery. Am J Ophthalmol 1984;98:313-9. 4. Schultz RO, Glasser DB, Matsuda M, Yee RW, Edelhauser HF. Response of the corneal endothelium to cataract surgery. Arch Ophthalmol 1986;104:1164-9. 5. Arshinoff SA. Why Healon5? The meaning of "viscoad aptive." Ophthalmic Pract 1999; 17(6):332-4. 6. Arshinoff SA. Healon5. In: Buratto L, Giardini P, Bellucci R, editors. Viscoelastics in ophthalmic surgery. Thorofare (NJ): Slack Inc; 2000. p. 393-400.
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7. Beiko G. Prospective study of endothelial cell loss and pachymetry following cataract surgery, using Healon GV, Amvisc Plus and Healon5. American Society of Cataract and Refractive Surgery meeting; 2001 Apr; San Diego. 8. Beiko G. Prospective study of Healon GV and Duo Vise, and endothelial cell loss and pachymetry following cata ract surgery. American Society of Cataract and Refractive Surgery meeting; 2000 May; Boston. 9. Beiko G. Prospective study of endothelial cell loss in cataract phacoemulsification, comparing Healon5 and Vis coat. American Academy of Ophthalmology meeting; 2001 Nov; New Orleans. 10. Ventura AC, Awalti R, Bohnke M. Corneal thickness and endothelial density before and after cataract surgery. Br J Ophthalmol 2001 ;85(1):18-20. 11. Amon M, Menapace R, Scheidel W. Results of corneal pachymetry after small-incision hydrogel lens implanta tion and scleral-step incision poly(methyl methacrylate) lens implantation following phacoemulsification. J Cataract Refract Surg 1991;17(4):466-70. 12. Beiko G. Prospective study of pachmetry on the first post operative day after cataract phacoemulsification, using Healon GV, Healon5 and I-Vise Phaco. European Society of Cataract and Refractive Surgery meeting; 2001 Sept; Amsterdam. 13. Landesz M, Siertsema JV, Van Rij G. Comparative study of three semiautomated specular microscopes. J Cataract Refract Surg 1995;21(4):409-16. 14. Ravalico G, Tognetto D, Baccara F, Lovisato A. Corneal endothelial protection by different viscoelastics during phacoemulsification. J Cataract Refract Surg 1997;23(3): 433-9. 15. Schwenn 0, Dick HB, Krummenauer F, Christmann S, Vogel A, Pfeiffer N. Healon5 versus Viscoat during cat aract surgery: intraocular pressure, laser flare and corneal changes. Graefes Arch Clin Exp Ophthalmol 2000; 238(10):861-7. 16. Holzer MP, Tetz MR, Auffarth GU, Welt R, Volcker HE. Effect of Healon5 and 4 other viscoelastic substances on intraocular pressure and endothelium after cataract surgery. J Cataract Refract Surg 2001;27:213-8. 17. Oxford Cataract Treatment and Evaluation Team. Long term corneal endothelial cell loss after cataract surgery; results of a randomized controlled trial. Arch Ophthalmol 1986; 104: 1170-5. 18. Ravalico G, Tognetto D, Palomba MA, Lovisato A, Baccara F. Corneal endothelial function after extracapsu lar cataract extraction and phacoemulsification. J Cataract Refract Surg 1997;23(7): 1000-5. 19. Lee JH, Oh SY. Corneal endothelial cell loss from suture fixation of a posterior chamber intraocular lens. J Cataract Refract Surg 1997;23(7): 1020-2. Key words: phacoemulsification, ophthalmic viscosurgical devices, endothelial cell count, corneal thickness