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Effect of cataract extraction with intraocular lens implantation on ocular hemodynamics
Effect of cataract extraction with intraocular lens implantation on ocular hemodynamics Christoph W. Spraul, MD, Josef Amann, MD, Gabriele E. Lang, MD, Gerhard K. Lang, MD ABSTRACT Purpose: To investigate the effect of cataract extraction on ocular hemodynamics. Setting: University Eye Clinic of Ulm, Germany. Methods: In 51 consecutive patients assigned for cataract surgery, pulse amplitude, pulse volume, and pulsatile ocular blood flow were measured 1 day before and 3 days and 12 months after cataract extraction using an ocular blood flow tonograph. Statistical analysis was performed with Student's t-test and Wilcoxon signed-rank test. Results: In the study eyes, 3 days after cataract surgery pulse amplitude, pulse volume, and pulsatile ocular blood flow had decreased from 2.5 to 2.1 mm Hg (P = .0014), 5.0 to 4.4 J.LI (P = .0059), and 836.2 to 728.0 J.LI/min (P = .0017), respectively. No statistically significant change between preoperative and 3 day postoperative measurements occurred in the fellow eyes. There was no significant difference in systemic blood pressure, heart rate, or lOP in study and fellow eyes before and 3 days after cataract surgery. The early reduction of pulse amplitude, pulse volume, and pulsatile ocular blood flow in the study eyes was not present 1 year postoperatively. Conclusion: Uncomplicated cataract extraction is associated with a temporary ipsilateral impairment of ocular hemodynamics. A neural mechanism triggered by cataract extraction may be involved in these temporary changes. J Cataract Refract Surg 1996; 22:1091-1096
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ataract extraction has become the most common ophthalmic surgical procedure. However, little is known about its effect on ocular hemodynamics, possibly because it is difficult to assess ocular blood flow. We used a modified Langham ocular blood flow system to study the effect of extracapsular cataract extraction with
implantation of a posterior chamber intraocular lens (IOL) on ocular hemodynamics. This instrument has been shown to be reliable 1 and valid2 and allows one to perform a noninvasive measurement quickly and easily.
From the University Eye Hospital and Clinic of Ulm, Department of Ophthalmology, Ulm, Germany.
We prospectively assessed ocular hemodynamics in 51 consecutive patients having cataract surgery on an inpatient basis at the University Eye Clinic ofUlm. Informed consent was obtained before the examination,
Reprint requests to Christoph W: Spraul, MD, Universitiits-Augenklinik und Poliklinik in Ulm, Prittwitzstrasse 43, 89075 Ulm, Germany.
Subjects and Methods
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and the study conformed to the principles established in the Declaration of Helsinki. Patients with a history of ocular trauma, intraocular surgery, glaucoma, and retinal vascular diseases were excluded, as were patients with significant cardiovascular diseases, arterial hypertension, carotid artery stenosis, and treatment with drugs influencing ocular blood flow. An ocular blood flow tonograph (OBF Labs Ltd.) fit with a newly developed probe was used. This instrument allows a high-fidelity recording of the intraocular pressure (lOP) pulse, which is caused by cardiac pulsation.3-8 The pulse amplitude (difference between the minimum and maximum lOP) is dependent on the amount ofblood transported into the eye during cardiac systole and the rigidity (elasticity) of the ocular walls. With the known pressure-volume relationship, 9 •10 the change of ocular volume as a function of time can be calculated. By differentiating this curve, the net pulsatile flow is obtained. 8' 11 ' 12 All measurements were performed in a standardized fashion with the patient in a sitting position. The tonograph fit in the Goldmann holder of the slitlamp. Blood pressure and pulse rate were recorded with each test. Both eyes were anesthetized with 0.4% oxybuprocaine hydrochloride (Novesine®). Five pulses were analyzed in real time to a standardized protocol. The net pulsatile ocular blood flow is calculated automatically during the test. Digital filtering and biasing were used in this realtime calculation to smooth breathing effects and to make calculations less volatile when the systolic and diastolic times were similar. Besides pulsatile ocular blood flow (p.llmin), the machine calculated maximum and minimum lOP (mm Hg), pulse amplitude (mm Hg), pulse volume (p.l), systolic time (sec), and diastolic time (sec). Data for each measurement were automatically stored on a disc. Measurements were performed 1 day before and 3 days and 12 months after surgery. Extracapsular cataract extraction was performed through a 6.0 mm scleral incision at 12 o'clock with a tunnel. After phacoemulsification, a posterior chamber IOL was implanted in the capsular bag. General anesthesia was performed using halothane (0.5 vol %) and nitrous oxide (65 vol %) and retrobulbar anesthesia consisted of an injection of 5 ml of meavarine (2%)-bupivacaine (0.5%) mixture with hyaluronidase and adrenalin (after-mixing concentration 1:500,000) and Vorosmarthy oculopression for 1092
15 minutes. Postoperative treatment consisted of gentamicin and dexamethasone (Dexamytrex®) and flurbiprofen (Ocuflur®). Distribution characteristics were assessed by calculating standardized coefficients of kurtosis. If the values for this parameter were within the -2.0 to + 2.0 range, indicating normal distribution, the Student's t-test was used. If they were outside this range, a Wilcoxon signedrank test was performed for statistical analysis. Spearman's rank-correlation test (correlation coefficient= r8 ) was used to determine a monotonic relationship between any two of the measured variables. A P-value below 0.006 (adjustment for multiple tests with Bonferroni correction) for Student's t-test or Wilcoxon signed-rank test and below 0.01 for Spearman's rank correlation was considered significant.
Results Fifty-one patients were included m the study. Twenty-five (49%) were women and 26 (51%), men. The mean age at time of surgery was 68.2 years (range 37 to 85 years). General anesthesia was used in 32 patients (63%) and retrobulbar, in 19 (37%). The mean measurements of all parameters are shown in Table 1. There was no significant difference between study and fellow eyes in systemic blood pressure, heart rate, and lOP before and 3 days after cataract surgery. However, in the study eyes, pulse amplitude, pulse volume, and pulsatile ocular blood flow had decreased from 2.5 to 2.1 mm Hg, 5.0 to 4.4 p.l, and 836.2 to 728.0 p.llmin, respectively, 3 days after surgery. The fellow eyes showed only a slight decrease in all parameters (Table 1). The differences between preoperative and postoperative pulse amplitude, pulse volume, and pulsatile ocular blood flow were not influenced by type of anesthesia (Table 2) or by patient age (Spearman's rank correlation; P-values between .221 and .790). In the study eyes, pulse amplitude, pulse volume, and pulsatile ocular blood flow increased significantly between 3 days and 12 months postoperatively, from 2.1 to 2.5 mm Hg (P = .0009), 4.4 to 5.3 p.l (P = .0029), and 728.0 to 811.3p.llmin (P= .0083), respectively. There was no significant difference in systemic blood pressure, heart rate, and lOP. In the study and the fellow eyes, there was no statistically significant differ-
J CATARACT REFRACT SURG-VOL 22, OCTOBER 1996
OCULAR HEMODYNAMICS AFTER ECCE AND IOL IMPLANTATION
Table 1. Measurements of all parameters before and 3 days after cataract extraction with IOL implantation (n =51). Mean Measurement ± 50 Parameter
Preoperative
Study eyes lOP (mm Hg) Pulse amplitude (mm Hg) Pulse volume (f.l.l) Pulsatile ocular blood flow (f.l.l/min)
16.9 2.5 5.0 836.2
:±: 4.5 :±: 1.0 :±: 1.8
Fellow eyes lOP (mm Hg) Pulse amplitude (mm Hg) Pulse volume (f.LI) Pulsatile ocular blood flow (f.LI/min)
16.4 2.4 4.9 830.8
:±: 4.1 :±: 0.9
.1 Pre-Post
P-value
4.4 1.1 2.2 292.6
-1.7% -12.9% -12.0% -12.9%
NS* .0014 .0059 .0017
17.0:±:2.9 2.4 :±: 1.1 4.7 :±: 2.4 799.1 :±: 357.8
+3.7% -0.5% -3.3% -3.8%
Postoperative
16.6 2.1 4.4 728.0
:±: 325.8
:±: 1.8 :±: 292.8
:±: :±: :±: :±:
NS NS NS NS
*NS = not significant
ence between the preoperative and the 12 month postoperative values of any parameter (Table 3).
Discussion The results of this study show that cataract extraction temporarily affects ocular hemodynamics. Pulse amplitude, pulse volume, and pulsatile ocular blood flow were significantly reduced in the early postoperative period. This reduction was not observed 1 year after cataract extraction. Axial length, heart rate, blood pressure, and lOP, which have been reported to influence the ocular Table 2. Differences in all parameters between preoperative and 3 day postoperative values by form of anesthesia.
pulse, 13- 15 did not differ significantly between examinations. Mathematically, total blood flow to the eye consists of the sum of the pulsatile and the nonpulsatile components; the flow distribution shows that uveal circulation accounts for 96% and retinal circulation for 4% of the total flow. 16 · 17 Analysis of the lOP pulse allows assessment of only the pulsatile component of the total ocular blood flow. Previous reports 2 ' 18 show that the pulse volume and the pulsatile ocular blood flow can be calculated in a theoretically satisfying way in absolute units from the pulsatile variations of the IOP?· 8 An important parameter for calculating absolute units for the Table 3.
Measurements of all parameters before and 12 months after cataract extraction with IOL implantation (n == 51).
Mean Measurement ± SD
Mean/Median Difference
Parameter Study eyes lOP (mm Hg) Pulse amplitude (mm Hg) Pulse volume (f.LI) Pulsatile ocular blood flow (f.l.l/min) Fellow eyes lOP (mm Hg) Pulse amplitude (mm Hg) Pulse volume (f.l-1) Pulsatile ocular blood flow (f.l.l/min) *NS
= not significant
General Anesthesia Retrobulbar Group Group (n = 19) P-value (n = 32)
0.1 0.37 0.77 109.6
0.6 0.22 0.32 105.7
-0.9
-0.7
0.2 0.5 44.0
0.1 0.7 28.0
NS* NS NS NS
NS NS NS NS
Parameter Study eyes lOP (mm Hg) Pulse amplitude (mm Hg) Pulse volume (f.l.l) Pulsatile ocular blood flow (f.l.l/min) Fellow eyes lOP (mm Hg) Pulse amplitude (mm Hg) Pulse volume (f.l.l) Pulsatile ocular blood flow (f.l.l/min) *NS
Preoperative
12 Months Postoperative
P-value
16.9 :±: 4.5 2.5 :±: 1.0
16.4 :±: 5.4 2.5 :±: 1.0
NS* NS
5.0 :±: 1.8 836.2 :±: 325.8
5.3 :±: 2.0 811.3 :±: 290.1
NS NS
17.6 :±: 3.9 2.6 :±: 1.1
NS NS
16.4 :±: 4.1 2.4 :±: 0.9 4.9 :±: 1.8 830.8 :±: 292.8
5.1 :±: 2.1 774.0 :±: 275.6
NS NS
= not significant
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pulse volume and the pulsatile ocular blood flow is the coefficient used for the pressure-volume relationship. This is crucial when comparing different groups of patients, especially with different lOP means, since the 19 coefficient seems to be dependent on the IOP. However, the absolute value of this coefficient is less important in repeated measurements of the same group, as in our study. It has been shown that modern cataract surgery using scleral incisions with a tunnel does not significantly change the pressure-volume relationship (unpublished data). There is considerable controversy about the ratio of pulsatile to non pulsatile flow and the significance of this . 1s-22 D oppc . · · cror tissue an d oxygenation. perruston ratio 20 ler recordings of the ophthalmic artery and the observation of rapidly decreasing pulse amplitude with 21 increasing IOP have been interpreted in such a way that the nonpulsatile flow is negligible compared with the pulsatile flow. Other authors have found a diastolic flow rate in the ophthalmic artery 18 ' 23 and even in reti4 nal arteriel and conclude that the nonpulsatile component accounts for approximately 50% of the total ocular blood flow. Animal studies show that pulsatile perfusion maintains better capillary and venous perfu25 sion than does non pulsatile blood flow, and some conclude that a shift toward nonpulsatile perfusion would not be beneficial and might reduce tissue perfusion and 22 oxygenation. Ischemic syndromes after cataract extraction have been described. 26 - 36 The most common is anterior ischemic optic neuropathy (AION), 27- 32 which has been reported to occur in 0.17% of cataract 26 extractions. This may be explained by the complex microcirculation and the lack of a sufficient autoregulation in the retrolaminar part of the optic nerve. Ischemic syndromes of other ocular structures are rare. Only a few reports of choroidal33 ' 34 ' 37 and retinal ischemia34 - 36 after cataract extraction have been published. The reason for the infrequency of ischemic syndromes in the latter areas may be the rich blood supply of the choroid and the autoregulation of the retina. Many factors can compromise ocular perfusion in the postoperative period. One often mentioned is a postoperative lOP rise. 26 •27 •30 •33 Other causes are directly or indirectly related to anesthesia. Direct causes are retrobulbar hemorrhage, spasm of central retinal artery, 35 and hematoma of the optic nerve sheaf. 36 Additionally, peribulbar and retrobulbar anesthesia cause reduction of 1094
systolic ciliary perfusion pressure, ocular blood pressure, and pulse volume; general anesthesia is associated with reduction of systolic ciliary and retinal perfusion pressure, systemic blood pressure, ocular pulse volume, and pulsatile ocular blood flow. 38 - 40 However, it is unlikely that these factors are responsible for the reduction of pulse amplitude, pulse volume, and pulsatile ocular blood flow observed in our study 3 days after surgery. Cataract extraction is known to activate phospholipase A2 and liberate arachidonic acid. This is followed by local production of prostaglandin, thromboxane, prostacyclin, and leukotriene. 41 .42 Significant levels of these substances are even found in uncomplicated cases 42 of cataract extraction 1 to 2 weeks after surgery. These mediators have complex biological effects, e.g., increasing aqueous humor production, increasing permeability of the blood-aqueous barrier, changing resistance of ves41 sels, and liberating other inflammatory mediators. Chronic production of these factors can cause cystoid 41 macular edema. Although a cyclo-oxygenase inhibitor was routinely applied before and after cataract surgery, products of the cyclo-oxygenase pathway (i.e., prostaglandin, thromboxane, prostacyclin) or products of the uninhibited lipoxygenase pathway (i.e., leukotrienes or other unknown humoral factors) may be the cause of the observed temporary change in ocular hemodynamics in our study. Other factors may also play a role. Animal studies have shown that unilateral stimulation of the sensory part of the trigeminal nerve can produce ipsilateral and contralateral changes in lOP and disruption of the blood-aqueous barrier that cannot be prevented by pretreatment with indometacin. 43 •44 A similar neural mechanism with involvement of the central nervous system may exist in humans. Cataract extraction may trigger a neural reaction that causes the changes observed in our study. Other possible causes, such as drugs (gentamicin, dexamethasone, flurbiprofen) applied in the postoperative period, are unlikely because these drugs have not been shown to be vasoactive or to influence ocular blood flow. In this study, uncomplicated cataract extraction was associated with an ipsilateral decrease in pulse amplitude, pulse volume, and pulsatile ocular blood flow. The magnitude of the pulsatile ocular blood flow decrease was 12.9% of the preoperative value. Because of retinal autoregulation and rich blood flow in the choroid, it is highly unlikely that this temporary decrease significantly
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OCULAR HEMODYNAMICS AFTER ECCE AND IOL IMPLANTATION
compromises tissue perfusion and oxygenation in those areas. However, the observed decrease in pulsatile ocular blood flow may be sufficient to cause ischemia in hemodynamically critical regions, i.e., the retrolaminar optic nerve, that could result in AION. This is even more likely because cataractous eyes have a lower pulsatile ocular blood flow than controls. 45 As clinical studies have shown that postcataract extraction AION is likely to occur also in the second eye after cataract extraction, 27 it is worthwhile to institute all possible prophylactic measures.
References 1. Spraul CW, Lang GE, Ronzani M, et al. Reliability of measurements with a new slit lamp mounted ocular blood flow tonograph. ARVO abstract 1998. Invest Ophthalmol Vis Sci 1995; 36:S436 2. Silver OM, Farrell RA. Validity of pulsatile ocular blood flow measurements. Surv Ophthalmol1994; 38(suppl): S72-S80 3. Phillips CI, Shaw TL. Model analysis of impression tonometry and tonography. Exp Eye Res 1970; 10:161182 4. Walker RE, Compton GA, Langham ME. Pneumatic applanation tonometer studies. IV. Analysis of pulsatile response. Exp Eye Res 1975; 20:245-253 5. Bill A. Intraocular pressure and blood flow through the uvea. Arch Ophthalmol1962; 67:336-348 6. Perkins ES. The ocular pulse. Curr Eye Res 1981; 1:19-23 7. Langham ME, Farrell RA, O'Brien V, et al. Blood flow in the human eye. Acta Ophthalmol1989; Suppl191 :9-13 8. Langham ME, Farrell RA, O'Brien V, et al. Non-invasive measurement of pulsatile blood flow in the human eye. In: Lambrou GN, Greve EL, eds, Ocular Blood Flow in Glaucoma; Means, Methods and Measurements. Amsterdam, Milano, Kugler & Ghedini 1989; 93-99 9. Eisenlohr JE, Langham ME, Maumenee AE. Manometric studies of the pressure-volume relationship in living and enucleated eyes of individual human subjects. Br J Ophthalmol1962; 46:536-548 10. Friedenwald JS. Contribution to the theoty and practice of tonometry. Am J Ophthalmol1937; 20:985-1024 11. Silver OM, Farrell RA, Langham ME. Estimation of pulsatile ocular blood flow from intraocular pressure. Acta Ophthalmol1989; Suppl191:25-29 12. Ktakau CET. Calculation of the pulsatile ocular blood flow. Invest Ophthalmol Vis Sci 1992; 33:2754-2756 13. Trew DR, James CB, Thomas SHL, et al. Factors influencing the ocular pulse-the heart rate. Graefes Arch Clin Exp Ophthalmol 1991; 229:553-556 14. James CB, Trew DR, Clark K, Smith SE. Factors influ-
encing the ocular pulse-axial length. Graefes Arch for Clin Exp Ophthalmol1991; 229:342-344 15. Lawrence C, Schlegel WA. Ophthalmic pulse studies. I. Influence of intraocular pressure. Invest Ophthalmol 1966; 5:515-525 16. Aim A, Bill A. Ocular and optic nerve blood flow at normal and increased intraocular pressure in monkeys (Macaca irus): a study with radioactively labelled microspheres including flow determinations in brain and some other tissues. Exp Eye Res 1973; 15:15-29 17. Bill A. Blood circulation and fluid dynamics in the eye. Physiol Rev 1975; 55:383-417 18. Krakau CET. A model for pulsatile and steady ocular blood flow. Graefes Arch Clin Exp Ophthalmol 1995; 233:112-118 19. YtteborgJ. The role of intraocular blood volume in rigidity measurements on human eyes. Acta Ophthalmol 1960; 38:410-436 20. Aaslid R. Transcranial Doppler Sonography. Vienna, New York, Springer-Verlag 1986; 51-54 21. Langham ME, To'mey KF. A clinical procedure for the measurements of the ocular pulse-pressure relationship and the ophthalmic arterial pressure. Exp Eye Res 1978; 27:17-25 22. H0rven I. Ophthalmic artery pressure during retrobulbar anaesthesia. Acta Ophthalmoll978; 56:574-586 23. Baxter GM, Williamson TH, McKillop G, Dutton GN. Color Doppler ultrasound of orbital and optic nerve blood flow: effects of posture and timolol 0.5%. Invest Ophthalmol Vis Sci 1992; 33:604-610 24. Feke GT, Tagawa H, Deupree OM, et al. Blood flow in the normal human retina. Invest Ophthalmol Vis Sci 1989; 30:58-65 25. Matsumo T, Wolferth CC Jr, Perlman MH. Effects of pulsatile and non-pulsatile perfusion upon cerebral and conjunctival microcirculation in dogs. Am Surg 1971; 37:61-64 26. Ruprecht KW, Naumann GOH. Uni- and bilaterale ischamische Papilleninfarkte nach Katarakt-Extraktion. Fortschr Ophthalmol1985; 82:349-352 27. Hayreh SS. Anterior ischemic optic neuropathy. IV. Occurrence after cataract extraction. Arch Ophthalmol 1980; 98:1410-1416 28. Serrano LA, Behrens MM, Carroll FD. Postcataract extraction ischemic optic neuropathy (letter). Arch Ophthalmol 1982; 100: 1177-1178 29. Carroll FD. Optic nerve complications of cataract extraction. Trans Am Acad Ophthalmol Otolaryngol 1973; 77:0P-623-0P-629 30. Michaels DO, Zugsmith GS. Optic neuropathy following cataract extraction. Ann Ophthalmol 1973; 5:303306 31. Oliver M. Posterior pole changes after cataract extraction
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OCULAR HEMODYNAMICS AFTER ECCE AND IOL IMPLANTATION
32.
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34.
35.
36.
37.
38.
39.
1096
in elderly subjects. Am J Ophthalmol 1966; 62:11451148 Welch RB, Cooper JC. Macular edema, papilledema, and optic atrophy after cataract extraction. Arch Ophthalmol1958; 59:665-675 Gass JDM, Parrish R. Outer retinal ischemic infarction-a newly recognized complication of cataract extraction and closed vitrectomy. Part 1. A case report. Ophthalmology 1982; 89:1467-1471 Meythaler FH, Naumann GOH. lntraokulare ischamische Infarkte bei lnjektionen in das Lid und parabulbar (ohne Bulbusperforation). Klin Monatsbl Augenheilkd 1987; 190:474-477 Klein ML, Jampol LM, Condon PI, et al. Central retinal artery occlusion without retrobulbar hemorrhage after retrobulbar anesthesia. Am J Ophthalmol1982; 93:573577 Sullivan KL, Brown GC, Forman AR, et a!. Retrobulbar anesthesia and retinal vascular obstruction. Ophthalmology 1983; 90:373-377 Rosenblum PD, Michels RG, Stark WJ, Taylor HR. Choroidal ischemia after extracapsular cataract extraction by phacoemulsification. Retina 1981; 1:263-270 Hessemer V. Anasthesie-Effekte auf den okularen Kreislauf; Synopsis einer Studie. Fortschr Ophthalmol1991; 88:577-587 Hessemer V, Wieth K, Jacobi KW, et al. Okulare Kreislaufreranderungen bei Halothan-Lachgas-lntubations narkose unter besonderer Berucksichtigung des arteriellen C0 2 -Partialdrucks. II. Mechanismen der Veranderungen. Klin Monatsbl Augenheilkd 1991; 199:424431
40. Hessemer V, Wieth K, Jacobi KW, eta!. Okulare Kreislaufreranderungen bei Halothan-Lachgas-lntubations narkose unter besonderer Berucksichtigung des arteriellen C0 2 -Partialdrucks. I. Phanomenologie der Veranderungen. Klin Monatsbl Augenheilkd 1991; 199:346355 41. Yannuzzi LA. A perspective on the treatment of aphakic cystoid macular edema. Surv Ophthalmol 1984; 28:540-553 42. Miyake K, Sugiyama S, Norimatsu I, Ozawa T. Prevention of cystoid macular edema after lens extraction by topical indometacin (III). Radioimmunoassay measurement of prostaglandins in the aqueous during and after lens extraction procedures. Albrecht von Graefes Arch Klin Exp Ophthalmol1978; 209:83-88 43. Perkins ES. Influence of the fifth cranial nerve on the intra-ocular pressure of the rabbit eye. Br J Ophthalmol 1957; 41:257-300 44. MaulE, Sears ML. The contralateral effect of antidromic stimulation of the trigeminal nerve on the rabbit eye. Invest Ophthalmol1976; 15:564-566 45. Hopkins SD. Ocular haemodynamics in cataractous eyes; a pilot study. Acta Ophthalmol Suppl 1989; 191: 43-48
None of the authors has a proprietary interest in the development or marketing ofthe instrument described or a competing instrument. Dr. Hans E. Grossniklaus assisted with this manuscript.
J CATARACT REFRACT SURG-VOL 22, OCTOBER 1996
C
ataract extraction has become the most common ophthalmic surgical procedure. However, little is known about its effect on ocular hemodynamics, possibly because it is difficult to assess ocular blood flow. We used a modified Langham ocular blood flow system to study the effect of extracapsular cataract extraction with
implantation of a posterior chamber intraocular lens (IOL) on ocular hemodynamics. This instrument has been shown to be reliable 1 and valid2 and allows one to perform a noninvasive measurement quickly and easily.
From the University Eye Hospital and Clinic of Ulm, Department of Ophthalmology, Ulm, Germany.
We prospectively assessed ocular hemodynamics in 51 consecutive patients having cataract surgery on an inpatient basis at the University Eye Clinic ofUlm. Informed consent was obtained before the examination,
Reprint requests to Christoph W: Spraul, MD, Universitiits-Augenklinik und Poliklinik in Ulm, Prittwitzstrasse 43, 89075 Ulm, Germany.
Subjects and Methods
J CATARACT REFRACT SURG-VOL 22, OCTOBER 1996
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OCULAR HEMODYNAMICS AFTER ECCE AND IOL IMPLANTATION
and the study conformed to the principles established in the Declaration of Helsinki. Patients with a history of ocular trauma, intraocular surgery, glaucoma, and retinal vascular diseases were excluded, as were patients with significant cardiovascular diseases, arterial hypertension, carotid artery stenosis, and treatment with drugs influencing ocular blood flow. An ocular blood flow tonograph (OBF Labs Ltd.) fit with a newly developed probe was used. This instrument allows a high-fidelity recording of the intraocular pressure (lOP) pulse, which is caused by cardiac pulsation.3-8 The pulse amplitude (difference between the minimum and maximum lOP) is dependent on the amount ofblood transported into the eye during cardiac systole and the rigidity (elasticity) of the ocular walls. With the known pressure-volume relationship, 9 •10 the change of ocular volume as a function of time can be calculated. By differentiating this curve, the net pulsatile flow is obtained. 8' 11 ' 12 All measurements were performed in a standardized fashion with the patient in a sitting position. The tonograph fit in the Goldmann holder of the slitlamp. Blood pressure and pulse rate were recorded with each test. Both eyes were anesthetized with 0.4% oxybuprocaine hydrochloride (Novesine®). Five pulses were analyzed in real time to a standardized protocol. The net pulsatile ocular blood flow is calculated automatically during the test. Digital filtering and biasing were used in this realtime calculation to smooth breathing effects and to make calculations less volatile when the systolic and diastolic times were similar. Besides pulsatile ocular blood flow (p.llmin), the machine calculated maximum and minimum lOP (mm Hg), pulse amplitude (mm Hg), pulse volume (p.l), systolic time (sec), and diastolic time (sec). Data for each measurement were automatically stored on a disc. Measurements were performed 1 day before and 3 days and 12 months after surgery. Extracapsular cataract extraction was performed through a 6.0 mm scleral incision at 12 o'clock with a tunnel. After phacoemulsification, a posterior chamber IOL was implanted in the capsular bag. General anesthesia was performed using halothane (0.5 vol %) and nitrous oxide (65 vol %) and retrobulbar anesthesia consisted of an injection of 5 ml of meavarine (2%)-bupivacaine (0.5%) mixture with hyaluronidase and adrenalin (after-mixing concentration 1:500,000) and Vorosmarthy oculopression for 1092
15 minutes. Postoperative treatment consisted of gentamicin and dexamethasone (Dexamytrex®) and flurbiprofen (Ocuflur®). Distribution characteristics were assessed by calculating standardized coefficients of kurtosis. If the values for this parameter were within the -2.0 to + 2.0 range, indicating normal distribution, the Student's t-test was used. If they were outside this range, a Wilcoxon signedrank test was performed for statistical analysis. Spearman's rank-correlation test (correlation coefficient= r8 ) was used to determine a monotonic relationship between any two of the measured variables. A P-value below 0.006 (adjustment for multiple tests with Bonferroni correction) for Student's t-test or Wilcoxon signed-rank test and below 0.01 for Spearman's rank correlation was considered significant.
Results Fifty-one patients were included m the study. Twenty-five (49%) were women and 26 (51%), men. The mean age at time of surgery was 68.2 years (range 37 to 85 years). General anesthesia was used in 32 patients (63%) and retrobulbar, in 19 (37%). The mean measurements of all parameters are shown in Table 1. There was no significant difference between study and fellow eyes in systemic blood pressure, heart rate, and lOP before and 3 days after cataract surgery. However, in the study eyes, pulse amplitude, pulse volume, and pulsatile ocular blood flow had decreased from 2.5 to 2.1 mm Hg, 5.0 to 4.4 p.l, and 836.2 to 728.0 p.llmin, respectively, 3 days after surgery. The fellow eyes showed only a slight decrease in all parameters (Table 1). The differences between preoperative and postoperative pulse amplitude, pulse volume, and pulsatile ocular blood flow were not influenced by type of anesthesia (Table 2) or by patient age (Spearman's rank correlation; P-values between .221 and .790). In the study eyes, pulse amplitude, pulse volume, and pulsatile ocular blood flow increased significantly between 3 days and 12 months postoperatively, from 2.1 to 2.5 mm Hg (P = .0009), 4.4 to 5.3 p.l (P = .0029), and 728.0 to 811.3p.llmin (P= .0083), respectively. There was no significant difference in systemic blood pressure, heart rate, and lOP. In the study and the fellow eyes, there was no statistically significant differ-
J CATARACT REFRACT SURG-VOL 22, OCTOBER 1996
OCULAR HEMODYNAMICS AFTER ECCE AND IOL IMPLANTATION
Table 1. Measurements of all parameters before and 3 days after cataract extraction with IOL implantation (n =51). Mean Measurement ± 50 Parameter
Preoperative
Study eyes lOP (mm Hg) Pulse amplitude (mm Hg) Pulse volume (f.l.l) Pulsatile ocular blood flow (f.l.l/min)
16.9 2.5 5.0 836.2
:±: 4.5 :±: 1.0 :±: 1.8
Fellow eyes lOP (mm Hg) Pulse amplitude (mm Hg) Pulse volume (f.LI) Pulsatile ocular blood flow (f.LI/min)
16.4 2.4 4.9 830.8
:±: 4.1 :±: 0.9
.1 Pre-Post
P-value
4.4 1.1 2.2 292.6
-1.7% -12.9% -12.0% -12.9%
NS* .0014 .0059 .0017
17.0:±:2.9 2.4 :±: 1.1 4.7 :±: 2.4 799.1 :±: 357.8
+3.7% -0.5% -3.3% -3.8%
Postoperative
16.6 2.1 4.4 728.0
:±: 325.8
:±: 1.8 :±: 292.8
:±: :±: :±: :±:
NS NS NS NS
*NS = not significant
ence between the preoperative and the 12 month postoperative values of any parameter (Table 3).
Discussion The results of this study show that cataract extraction temporarily affects ocular hemodynamics. Pulse amplitude, pulse volume, and pulsatile ocular blood flow were significantly reduced in the early postoperative period. This reduction was not observed 1 year after cataract extraction. Axial length, heart rate, blood pressure, and lOP, which have been reported to influence the ocular Table 2. Differences in all parameters between preoperative and 3 day postoperative values by form of anesthesia.
pulse, 13- 15 did not differ significantly between examinations. Mathematically, total blood flow to the eye consists of the sum of the pulsatile and the nonpulsatile components; the flow distribution shows that uveal circulation accounts for 96% and retinal circulation for 4% of the total flow. 16 · 17 Analysis of the lOP pulse allows assessment of only the pulsatile component of the total ocular blood flow. Previous reports 2 ' 18 show that the pulse volume and the pulsatile ocular blood flow can be calculated in a theoretically satisfying way in absolute units from the pulsatile variations of the IOP?· 8 An important parameter for calculating absolute units for the Table 3.
Measurements of all parameters before and 12 months after cataract extraction with IOL implantation (n == 51).
Mean Measurement ± SD
Mean/Median Difference
Parameter Study eyes lOP (mm Hg) Pulse amplitude (mm Hg) Pulse volume (f.LI) Pulsatile ocular blood flow (f.l.l/min) Fellow eyes lOP (mm Hg) Pulse amplitude (mm Hg) Pulse volume (f.l-1) Pulsatile ocular blood flow (f.l.l/min) *NS
= not significant
General Anesthesia Retrobulbar Group Group (n = 19) P-value (n = 32)
0.1 0.37 0.77 109.6
0.6 0.22 0.32 105.7
-0.9
-0.7
0.2 0.5 44.0
0.1 0.7 28.0
NS* NS NS NS
NS NS NS NS
Parameter Study eyes lOP (mm Hg) Pulse amplitude (mm Hg) Pulse volume (f.l.l) Pulsatile ocular blood flow (f.l.l/min) Fellow eyes lOP (mm Hg) Pulse amplitude (mm Hg) Pulse volume (f.l.l) Pulsatile ocular blood flow (f.l.l/min) *NS
Preoperative
12 Months Postoperative
P-value
16.9 :±: 4.5 2.5 :±: 1.0
16.4 :±: 5.4 2.5 :±: 1.0
NS* NS
5.0 :±: 1.8 836.2 :±: 325.8
5.3 :±: 2.0 811.3 :±: 290.1
NS NS
17.6 :±: 3.9 2.6 :±: 1.1
NS NS
16.4 :±: 4.1 2.4 :±: 0.9 4.9 :±: 1.8 830.8 :±: 292.8
5.1 :±: 2.1 774.0 :±: 275.6
NS NS
= not significant
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OCULAR HEMODYNAMICS AFTER ECCE AND IOL IMPLANTATION
pulse volume and the pulsatile ocular blood flow is the coefficient used for the pressure-volume relationship. This is crucial when comparing different groups of patients, especially with different lOP means, since the 19 coefficient seems to be dependent on the IOP. However, the absolute value of this coefficient is less important in repeated measurements of the same group, as in our study. It has been shown that modern cataract surgery using scleral incisions with a tunnel does not significantly change the pressure-volume relationship (unpublished data). There is considerable controversy about the ratio of pulsatile to non pulsatile flow and the significance of this . 1s-22 D oppc . · · cror tissue an d oxygenation. perruston ratio 20 ler recordings of the ophthalmic artery and the observation of rapidly decreasing pulse amplitude with 21 increasing IOP have been interpreted in such a way that the nonpulsatile flow is negligible compared with the pulsatile flow. Other authors have found a diastolic flow rate in the ophthalmic artery 18 ' 23 and even in reti4 nal arteriel and conclude that the nonpulsatile component accounts for approximately 50% of the total ocular blood flow. Animal studies show that pulsatile perfusion maintains better capillary and venous perfu25 sion than does non pulsatile blood flow, and some conclude that a shift toward nonpulsatile perfusion would not be beneficial and might reduce tissue perfusion and 22 oxygenation. Ischemic syndromes after cataract extraction have been described. 26 - 36 The most common is anterior ischemic optic neuropathy (AION), 27- 32 which has been reported to occur in 0.17% of cataract 26 extractions. This may be explained by the complex microcirculation and the lack of a sufficient autoregulation in the retrolaminar part of the optic nerve. Ischemic syndromes of other ocular structures are rare. Only a few reports of choroidal33 ' 34 ' 37 and retinal ischemia34 - 36 after cataract extraction have been published. The reason for the infrequency of ischemic syndromes in the latter areas may be the rich blood supply of the choroid and the autoregulation of the retina. Many factors can compromise ocular perfusion in the postoperative period. One often mentioned is a postoperative lOP rise. 26 •27 •30 •33 Other causes are directly or indirectly related to anesthesia. Direct causes are retrobulbar hemorrhage, spasm of central retinal artery, 35 and hematoma of the optic nerve sheaf. 36 Additionally, peribulbar and retrobulbar anesthesia cause reduction of 1094
systolic ciliary perfusion pressure, ocular blood pressure, and pulse volume; general anesthesia is associated with reduction of systolic ciliary and retinal perfusion pressure, systemic blood pressure, ocular pulse volume, and pulsatile ocular blood flow. 38 - 40 However, it is unlikely that these factors are responsible for the reduction of pulse amplitude, pulse volume, and pulsatile ocular blood flow observed in our study 3 days after surgery. Cataract extraction is known to activate phospholipase A2 and liberate arachidonic acid. This is followed by local production of prostaglandin, thromboxane, prostacyclin, and leukotriene. 41 .42 Significant levels of these substances are even found in uncomplicated cases 42 of cataract extraction 1 to 2 weeks after surgery. These mediators have complex biological effects, e.g., increasing aqueous humor production, increasing permeability of the blood-aqueous barrier, changing resistance of ves41 sels, and liberating other inflammatory mediators. Chronic production of these factors can cause cystoid 41 macular edema. Although a cyclo-oxygenase inhibitor was routinely applied before and after cataract surgery, products of the cyclo-oxygenase pathway (i.e., prostaglandin, thromboxane, prostacyclin) or products of the uninhibited lipoxygenase pathway (i.e., leukotrienes or other unknown humoral factors) may be the cause of the observed temporary change in ocular hemodynamics in our study. Other factors may also play a role. Animal studies have shown that unilateral stimulation of the sensory part of the trigeminal nerve can produce ipsilateral and contralateral changes in lOP and disruption of the blood-aqueous barrier that cannot be prevented by pretreatment with indometacin. 43 •44 A similar neural mechanism with involvement of the central nervous system may exist in humans. Cataract extraction may trigger a neural reaction that causes the changes observed in our study. Other possible causes, such as drugs (gentamicin, dexamethasone, flurbiprofen) applied in the postoperative period, are unlikely because these drugs have not been shown to be vasoactive or to influence ocular blood flow. In this study, uncomplicated cataract extraction was associated with an ipsilateral decrease in pulse amplitude, pulse volume, and pulsatile ocular blood flow. The magnitude of the pulsatile ocular blood flow decrease was 12.9% of the preoperative value. Because of retinal autoregulation and rich blood flow in the choroid, it is highly unlikely that this temporary decrease significantly
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OCULAR HEMODYNAMICS AFTER ECCE AND IOL IMPLANTATION
compromises tissue perfusion and oxygenation in those areas. However, the observed decrease in pulsatile ocular blood flow may be sufficient to cause ischemia in hemodynamically critical regions, i.e., the retrolaminar optic nerve, that could result in AION. This is even more likely because cataractous eyes have a lower pulsatile ocular blood flow than controls. 45 As clinical studies have shown that postcataract extraction AION is likely to occur also in the second eye after cataract extraction, 27 it is worthwhile to institute all possible prophylactic measures.
References 1. Spraul CW, Lang GE, Ronzani M, et al. Reliability of measurements with a new slit lamp mounted ocular blood flow tonograph. ARVO abstract 1998. Invest Ophthalmol Vis Sci 1995; 36:S436 2. Silver OM, Farrell RA. Validity of pulsatile ocular blood flow measurements. Surv Ophthalmol1994; 38(suppl): S72-S80 3. Phillips CI, Shaw TL. Model analysis of impression tonometry and tonography. Exp Eye Res 1970; 10:161182 4. Walker RE, Compton GA, Langham ME. Pneumatic applanation tonometer studies. IV. Analysis of pulsatile response. Exp Eye Res 1975; 20:245-253 5. Bill A. Intraocular pressure and blood flow through the uvea. Arch Ophthalmol1962; 67:336-348 6. Perkins ES. The ocular pulse. Curr Eye Res 1981; 1:19-23 7. Langham ME, Farrell RA, O'Brien V, et al. Blood flow in the human eye. Acta Ophthalmol1989; Suppl191 :9-13 8. Langham ME, Farrell RA, O'Brien V, et al. Non-invasive measurement of pulsatile blood flow in the human eye. In: Lambrou GN, Greve EL, eds, Ocular Blood Flow in Glaucoma; Means, Methods and Measurements. Amsterdam, Milano, Kugler & Ghedini 1989; 93-99 9. Eisenlohr JE, Langham ME, Maumenee AE. Manometric studies of the pressure-volume relationship in living and enucleated eyes of individual human subjects. Br J Ophthalmol1962; 46:536-548 10. Friedenwald JS. Contribution to the theoty and practice of tonometry. Am J Ophthalmol1937; 20:985-1024 11. Silver OM, Farrell RA, Langham ME. Estimation of pulsatile ocular blood flow from intraocular pressure. Acta Ophthalmol1989; Suppl191:25-29 12. Ktakau CET. Calculation of the pulsatile ocular blood flow. Invest Ophthalmol Vis Sci 1992; 33:2754-2756 13. Trew DR, James CB, Thomas SHL, et al. Factors influencing the ocular pulse-the heart rate. Graefes Arch Clin Exp Ophthalmol 1991; 229:553-556 14. James CB, Trew DR, Clark K, Smith SE. Factors influ-
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40. Hessemer V, Wieth K, Jacobi KW, eta!. Okulare Kreislaufreranderungen bei Halothan-Lachgas-lntubations narkose unter besonderer Berucksichtigung des arteriellen C0 2 -Partialdrucks. I. Phanomenologie der Veranderungen. Klin Monatsbl Augenheilkd 1991; 199:346355 41. Yannuzzi LA. A perspective on the treatment of aphakic cystoid macular edema. Surv Ophthalmol 1984; 28:540-553 42. Miyake K, Sugiyama S, Norimatsu I, Ozawa T. Prevention of cystoid macular edema after lens extraction by topical indometacin (III). Radioimmunoassay measurement of prostaglandins in the aqueous during and after lens extraction procedures. Albrecht von Graefes Arch Klin Exp Ophthalmol1978; 209:83-88 43. Perkins ES. Influence of the fifth cranial nerve on the intra-ocular pressure of the rabbit eye. Br J Ophthalmol 1957; 41:257-300 44. MaulE, Sears ML. The contralateral effect of antidromic stimulation of the trigeminal nerve on the rabbit eye. Invest Ophthalmol1976; 15:564-566 45. Hopkins SD. Ocular haemodynamics in cataractous eyes; a pilot study. Acta Ophthalmol Suppl 1989; 191: 43-48
None of the authors has a proprietary interest in the development or marketing ofthe instrument described or a competing instrument. Dr. Hans E. Grossniklaus assisted with this manuscript.
J CATARACT REFRACT SURG-VOL 22, OCTOBER 1996