Fluid Dynamics in Eyes With Rhegmatogenous Retinal Detachments Shunji Tsuboi, M.D., [un Taki-Noie, M.D.; Kazuyuki Emi, M.D., and Reizo Manabe, M.D.
Inward and outward permeabilities to sodium fluorescein at the blood-retinal barrier were measured by kinetic vitreous fluorophotometry in ten eyes with rhegmatogenous retinal detachments. Fellow eyes were used as controls. Inward permeability of eyes with detachments was significantly larger than that of controls (P<.OOS), suggesting damage to the blood-retinal barrier in eyes with detachments. Outward permeability of eyes with detachment and retinal holes was slightly less than that of controls, but the difference was not statistically significant. However, outward permeability of eyes with detachments and with ~etinal tears was significantly larger than that of controls (P<.OS). This increased outward permeability may be attributed to the increased fluid Oow posteriorly through the break across the retinal pigment epithelium. CLOSURE OF THE RETINAL BREAK is the rationale for repairing retinal detachment. Once the break is closed, the fluid between the sensory retina and retinal pigment epithelium is absorbed spontaneously. This phenomenon may be consistent with the posteriorly directed fluid flow through the retinal break across the retinal pigment epithelium, and has been described recently with an experimental retinal detachment model in the monkey.' However, the fluid movement in the retinal detachment of a living human eye has not been established.t" We measured the inward and outward retinal permeabilities to sodium fluorescein in retinal detachment by means of kinetic vitreous fluorophotometry,
Accepted for publication March 19, 1985. From the Department of Ophthalmology, Osaka University Medical School, Osaka, Japan. This study was supported in part by grant 58771187 from the Ministry of Education, Japan. Reprint requests to Shunji Tsuboi, M.D., Department of Ophthalmology, University of Minnesota, 9-240 Health Sciences Unit C, Box 493 Mayo Memorial Bldg., 516 Delaware SI. S.E., Minneapolis, MN 55455.
©AMERICAN JOURNAL
OF
to clarify the fluid dynamics in normal eyes and eyes with retinal detachment.
Subjects and Methods Kinetic vitreous fluorophotometry was performed on ten patients with unilateral rhegmatogenous retinal detachment before they underwent surgery and on eight after surgery. We excluded any patient with total retinal detachment, combined massive choroidal detachment, severe myopia (-8 diopters or more), macular hole, primary glaucoma, aphakia, or diabetes. For data processing, we used an optimization program correcting for autofluorescence and tailing effect." The fluorophotometric measurements were performed for both eyes before and two minutes, one hour, two hours, four hours, and six hours after intravenous injection of sodium fluorescein (7 mg/kg of body weight). Fifteen and 60 minutes after injection, 1 ml of blood was collected. The supernatant was diluted 100 to 400 times with buffered saline to determine the fluorescein concentration in plasma. We then calculated the decay of blood plasma fluorescein concentration as a function of time. Determination of the inward and outward permeabilities has been described previously. 6·8 Briefly, inward permeability was calculated from the measurement done one hour after injection. The amount of fluorescein in a cone within the vitreous cavity was attributed to the appearance of fluorescein in one hour across the blood-retinal barrier.v? The amount of fluorescein in the cone one hour after injection was divided by 60 (mean free fluorescein concentration in plasma during the first one hour) to determine the inward permeability in centimeters per minute. The ratio of free to whole fluorescein in plasma was determined to be 0.12. 9 When the fluorescein concentration 2 mm from the retina reaches its highest value, inward fluorescein
OPHTHALMOLOGY 99:673-676, JUNE, 1985
673
674
June, 1985
AMERICAN JOURNAL OF OPHTHALMOLOGY
flux is equivalent to outward fluorescein flux." Therefore, outward permeability x Cv = inward permeability x Cp, where Cv and Cp are free fluorescein concentrations in the vitreous and plasma at this time. Outward permeability was determined from this equation.
the eyes with retinal detachment was characterized by the shape of the retinal break. The mean outward permeability of eyes with retinal tears was significantly larger than that of fellow eyes (P<.05 by paired t-test), whereas it was somewhat lower in those with peripheral holes. A week after surgery, the increased outward permeability of eyes with tears decreased to a value similar to that of fellow eyes.
Results The mean (± S.D.) inward permeability value for all ten eyes with retinal detachment (Table) was 8.4 ± 3.1 x 10- 6 em/min, which was significantly larger than that of fellow eyes (5.9 ± 2.0 x 10- 6 em/min; P<.005 by paired r-test). Although the inward permeability of fellow eyes was larger in eyes with peripheral tears than in those with peripheral holes (P<.02 by unpaired t-test), there was an uneven distribution of age. After reattachment surgery, the inward permeability of the retinal detachment eyes remained increased. The mean (± S.D.) outward permeability value in all ten fellow eyes was 10.1 ± 2.4 x 10- 5 em/min, which was 17 times larger than the inward permeability of the same eyes. The outward permeability of
Discussion The increased inward permeability in eyes with retinal detachment, regardless of the shape of the retinal break, indicated damage to the blood-retinal barrier in these eyes. Increased permeability to fluorescein at the blood-retinal barrier (retinal capillary and retinal pigment epithelium) rather than the physical separation of the sensory retina from the retinal pigment epithelium may be the cause of the increased inward permeability, because it did not immediately come into normal range after reattachment. On the contrary, inward permeability after surgery increased in six of eight cases, probably
TABLE OUTWARD
INWARD AND
PERMEABILITY OUTWARD PERMEABILITY!
INWARD PERMEABILITY'
AFFECTED EYE
AFFECTED EYE PATIENT NO.,SEX, AGE (YRS)
Retinal tears 1, M, 64 2, F,61 3, F,34 4, F,45 5, M, 65 Mean ± S.D. Retinal holes 6, M, 30 7, M, 31 8, M, 54 9, M, 18 10, F,20 Mean ± S.D.
FELLOW EYE
BEFORE SURGERY
AFTER SURGERY
5.3 8.7 6.6 9.8 6.4 7.4 ±1.6
8.2 8.3 7.5 14.4 12.8 10.2 ±12.8
10.8 13.2 9.0 8.5
5.3 3.7 5.6 3.9 3.3 4.4 ±0.9
9.1 6.5 8.5 3.9 4.5 6.5 ±2.1
'Inward permeability (x 10- 6 em/min). 'Outward permeability (x 10- 5 em/min).
10.4 ±1.8 16.2 6.2 9.1 6.2 9.4 ±4.1
FELLOW EYE
BEFORE SURGERY
10.8 14.1 9.2 12.2 9.4 11.1 ±1.8
36.5 38.7 12.6 16.5 25.2 25.9 ±10.4
12.1 6.7 7.2 12.3 7.3 9.1 ±2.5
7.6 4.1 9.9 3.1 6.7 6.3 ±2.4
AFTER SURGERY
5.2 33.6 9.4 13.1 15.3 ±10.9 10.2 2.2 16.4 3.8 8.2 ±5.6
Vol. 99, No.6
Fluid Dynamics in Retinal Detachment
because of the retinal inflammation after cryoapplication which disrupts the blood-retinal barrier. Fluorescein moves by diffusion, transport, and bulk flow across the blood-retinal barrier. Active outward transport of fluorescein across the retina in rabbits" and across the retinal pigment epithelium in dogs" has been described. The decrease in outward permeability in eyes with retinal detachment and retinal holes may be proportional to the decrease in the active transport process at the blood-retinal barrier, but the increased diffusion into the eye may also participate in the decreased outward permeability in these cases. It seemed likely that the separation between the sensory retina and retinal pigment epithelium caused the functional damage in both of them. Conversely, the increased outward permeability in retinal detachments with tears may be indirect evidence for increased bulk flow posteriorly out of the eye, because increased diffusional inflow of fluorescein (deduced from the increased inward permeability in the same eyes) would have resulted in decreased outward permeability as was observed in eyes with retinal holes. This is supported by the return to normal range of outward permeability one week after surgery when increased diffusional permeability of the blood-retinal barrier still existed. In the monkey eye, only the bulk flow posteriorly-and
Fig. 1 (Tsuboi and associates). Posterior vitreous detachment in retinal detachment with tear allows humor and fluorescein to move freely through the tear.
675
Fig. 2 (Tsuboi and associates). Vitreous cavity in retinal detachment with hole is full of solid vitreous, so that the movement of fluorescein and possibly vitreous humor is restricted.
not diffusion-was significantly increased in experimental retinal detachment. 12 The difference in outward permeability between retinal detachment with tears and retinal detachment with holes may be attributed to the vitreous body which may cause variability in the vitreous fluorophotometry." Retinal detachments with tears occur rapidly with the collapse of the vitreous body, pulling the peripheral retina and causing tears." Thus, they are accompanied by posterior vitreous detachment (Fig. 1). In contrast, retinal detachments with holes progress gradually, without remarkable posterior vitreous detachment. Biomicroscopic examination disclosed that there were no posterior vitreous detachments in eyes with peripheral holes (Fig. 2). In the former case fluorescein was mixed with vitreous humor in the posterior one half of the vitreous cavity, so fluorescein, with a current of the vitreous humor, moved freely through the tear into the subretinal space and across the retinal pigment epithelium, which regulates the movement of ions;" fluorescein," and water. 16 Machemer" reviewed the importance of the fluid flow through the break in retinal detachment. Preoperative measurement of outward permeability to sodium fluorescein at the blood-retinal barrier in retinal detachment may be valuable, because it permits
676
AMERICAN JOURNAL OF OPHTHALMOLOGY
the fluid flow across the retinal pigment epithelium to be estimated.
References 1. Pederson, J. E., and Cantrill, H. 1.: Experimental retinal detachment. V. Fluid movement through the retinal hole. Arch. Ophthalmol. 102:136, 1984. 2. Dobbie, J. G.: A study of the intraocular fluid dynamics in retinal detachment. Arch. Ophthalmol. 69:159, 1963. 3. Regan, C. D. J., and Rousseau, A. P.: Ihe intraocular dynamics of eyes with retinal detachment. Am. J. Ophthalmol. 61:696, 1966. 4. Langham, M. E., and Regan, C. D. J.: Circulatory changes associated with onset of primary retinal detachment. Arch. Ophthalmol. 81:820, 1969. 5. Zeirner, R. c.. Blair, N. P., and Cunha-Vaz, J. G.: Vitreous fluorophotometry for clinical research. II. Method of data acquisition and processing. Arch. Ophthalmol. 101:1757, 1983. 6. - - - : Pharmacokinetic interpretation of vitreous fluorophotometry. Invest. Ophthalmol. Vis. Sci. 24:1374, 1983. 7. Tsuboi, 5.: Problems in analyzing vitreous fluorophotometry. Folia Ophthalmol. [pn. 35:2142, 1984. 8. Blair, N. P., Zeirner, R. c.. Rusin, M. M., and CunhaVaz, J. G.: Outward transport of fluorescein from the vitreous in normal human subjects. Arch. Ophthalmol. 101:1117, 1983.
June, 1985
9. Araie, M., and Matsumoto,S.: An analysis of fluorescein dynamics in the plasma after intravenous injection and calculation of the permeability of the blood-aqueous barrier. Acta Soc. Ophthalmol. [pn. 87:403, 1983. 10. Cunha-Vaz, J. G., and Maurice, D. M.: Ihe active transport of fluorescein by the retinal vessels and the retina. ]. PhysioL 191:467, 1967. 11. Tsuboi, 5., Fujimoto, I., Uchihori, Y., Erni, K., Iizuka, 5., Kishida, K., and Manabe, R.: Measurement of retinal permeability to sodium fluorescein in vitro. Invest. Ophthalmol. Vis. Sci. 25:1146, 1984. 12. Cantrill, H. 1., and Pederson, J. E.: Experimental retinal detachment. VI. Ihe permeability of the blood-retinal barrier. Arch. Ophthalmol. 102:747, 1984. 13. Prager, T. C.; Chu, H., Garcia, C. A., and Anderson, R. E.: The influence of vitreous change on vitreous flu orophotometry. Arch. Ophthalmol. 100:594, 1982. 14. Jaffe, N. 5.: Complications of acute posterior vitreous detachment. Arch. Ophthalmol. 79:568, 1968. 15. Lasansky, A., and De Fisch, F. W.: Potential, current and ionic fluxes across the isolated retinal pigment epithelium and choroid. J. Gen. Physiol. 49:913, 1966. 16. Miller, S. 5., Hughes, B. A., and Machen, I. E.: Fluid transport across retinal pigment epithelium is inhibited by cyclic AMP. Proc. Natl. Acad. Sci. U.s.A. 79:2111, 1982. 17. Machemer, R.: The importance of fluid absorption, traction, intraocular currents, and chorioretinal scars in the therapy of rhegmatogenous retinal detachments. XLI Edward Jackson Memorial Lecture. Am. J. Ophthalmol. 98:681, 1984.