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Intraocular Irrigating Solutions and Lens Clarity
INTRAOCULAR IRRIGATING SOLUTIONS AND LENS CLARITY J O H N M. C H R I S T I A N S E N , M.D., C A R O L R. K O L L A R I T S , M.D., H E N R Y F U K U I , P H . D . , AND M A R T I N L. F I S H M A N , M.D.
Bethesda, Maryland R O N A L D G. M I C H E L S ,
M.D.
Baltimore, Maryland AND I. M I K U N I , Bethesda,
Surgical techniques such as pars plana vitrectomy may involve prolonged peri ods of intraocular irrigation with large volumes of solution. No commercially available sterile solution has been formu lated specifically for prolonged intra ocular irrigation. The solutions common ly used during vitrectomy are Ringer's injection and Ringer's lactate (chemical composition given in the Table). Intraop erative cataract formation (in cases where lens removal is not indicated) and tran sient postoperative corneal decompen sation indicate that prolonged irrigation with these solutions is damaging to ocular tissues. Edelhauser and associates 1 have re cently developed a glutathione-bicarbonate-Ringer solution (G-B-R) that pro tects corneal endothelial function and ultrastructure during in vitro perfusion studies for up to six hours. To evaluate the effects of G-B-R and other irrigating solutions on lens clarity in vitro, monkey lenses were incubated at 37°C and exam-
From the Clinical Branch (Drs. Christiansen, Kol larits, and Fishman) and the Laboratory of Vision Research (Drs. Fukui and Mikuni), National Eye Institute, National Institutes of Health, Department of Health, Education and Welfare, Bethesda, Mary land, and the Wilmer Eye Institute, Johns Hopkins Hospital (Dr. Michels), Baltimore, Maryland. Reprint requests to Carol Kollarits, M.D., Clinical Branch, National Eye Institute, National Institutes of Health, Bethesda, MD 20014.
M.D.
Maryland
ined for evidence of cataract formation. Our purpose was to find an irrigating solution that could be prepared from commercially available stock solutions in the operating room and would be effec tive in maintaining lens clarity during prolonged intraocular surgery. M A T E R I A L AND M E T H O D S
Lenses were removed from 50 enucleat ed rhesus monkey eyes, taking care to minimize trauma. Isolated lenses were incubated in sterile Petri dishes contain ing 4.0 ml of irrigating solution at 37°C. One of each pair of lenses was incubated in a different solution to serve as a con trol. The Table lists the chemical compo sition of the irrigating solutions with their p H and osmolarity. The G-B-R solution was prepared here. The Ringer's injec tion, Ringer's lactate, 5% dextrose in wa ter, and sodium bicarbonate are commer cially available sterile solutions. A sodi um bicarbonate buffer system and 5.5 mM glucose (dextrose) were present in normal aqueous. 2 By aseptically injecting 18.0 ml of 5% dextrose in water and 20.0 ml of sodium bicarbonate (available as 50 m E q in 50 ml of water) into a standard 1,000-ml intravenous solution bottle of Ringer's injection or Ringer's lactate, so lutions were obtained that approached the glucose and bicarbonate concentra tions of G-B-R without an excessive in crease in osmolarity. The alkaline p H of
594
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INTRAOCULAR IRRIGATING SOLUTIONS
595
TABLE CHEMICAL COMPOSITION O F IRRIGATING SOLUTIONS
Ringer's Injection Solution, mM/1
Ringer's Lactate Solution, mM/1
111.56 4.82 1.04 0.78 0.86 29.20 5.01 0.50 0.30
147.00 4.00 1.00
103.40 4.05 0.60
306 7.40
309 5.80
G-B-R Solution, mM/1 Sodium chloride Potassium chloride Calcium chloride Magnesium chloride Sodium phosphate Sodium bicarbonate Glucose Adenosine Reduced glutathione Sodium lactate Osmolarity (mOsm/1) pH
-
-
-
28.00 273 6.70
D-5-W an d NaHCOa* in Ringer's Ringer's Lactate Injection Solution,f Solution.t mM/1 mM/1 147.00 4.00 1.00
103.40 4.05 0.60
20.00 5.00
20.00 5.00
310 8.03
28.00 278 8.15
-
-
*D-5-W (dextrose 5% in water) and NaHC0 3 (sodium bicarbonate) were added to these solutions. t These solutions can be prepared aseptically in the operating room by injecting 18.0 ml of commençai 5% dextrose in water and 20.0 ml of sodium bicarbonate solution (available in 50-ml ampules containing 50 mEq of sodium bicarbonate) into a 1,000-ml bottle of Ringer's injeclion or Ringer's lactate solution.
these solutions could be lowered to 7.4 by gassing with carbon dioxide but this step was found to be unnecessary. The incubating lenses were examined at four hours, 24 hours, and 48 hours for evidence of cataract formation. We per formed microscopic examination (lOx) of each lens, placing the Petri dish on a dark-background Amsler grid to facilitate detection of opacities. A lens without cortical or posterior opacities was desig nated "clear." A "cloudy" lens showed diffuse cortical haziness. This diffusely opaque cataract was tabulated separately from posterior stellate or leaf-shaped opacities because these leaf-shaped opac ities sometimes cleared spontaneously during further incubation. RESULTS
Four hours' incubation—Incubation of monkey lenses in G-B-R solution at 37°C resulted in 100% maintenance of lens clarity at four hours. No posterior changes were observed. Incubation of the lenses in Ringer's
injection solution resulted in only 10% of the lenses remaining clear at four hours. The addition of 5% dextrose in water as an energy source improved the mainte nance of lens clarity to the 20% level. Addition of the sodium bicarbonate buff er system without 5% dextrose in water increased the level to 40% (Fig. 1). The addition of both 5% dextrose in water and sodium bicarbonate produced a dramatic increase in the ability of Ringer's injec tion solution to maintain lens clarity. Sev enty percent of lenses were clear at four hours, and if lenses with posterior (re versible) changes are included, the level is 90%. Ringer's lactate solution contain ing 5% dextrose in water and sodium bicarbonate was also tested. While the percentage of clear lenses was higher for the Ringer's injection mixture at four hours, inclusion of the posterior lens opacities increases the percentage for the Ringer's lactate mixture. There was no significant difference between the mix ture based on either Ringer's injection or Ringer's lactate solutions at four or 24
596
AMERICAN JOURNAL OF OPHTHALMOLOGY
OCTOBER, 1976
Fig. 1 (Christiansen and associ ates). Maintenance of lens clarity after four hours of incubation at 37°C in different solutions. D5W indicates 5% dextrose in water; N a H C 0 3 , sodium bicarbonate; PSC, posterior subcapsular cataract; and Total indicates clear lenses and lenses with cataracts.
hours of incubation. These mixtures were also gassed with carbon dioxide to a p H of 7.40 without apparent improvement in effectiveness. Twenty-four hours' incubation—At 24 hours, all of the lenses incubated in G-B-R solution remained clear. After 24 hours of incubation, all of the lenses in unsupplemented Ringer's injection and Ringer's lactate solutions were cataractous. The addition of either 5% dextrose in water or sodium bicarbonate did not improve the result. When both 5% dex trose in water and sodium bicarbonate were added to Ringer's injection or Ring er's lactate solutions, a marked increase in the ability of these solutions to maintain
lens clarity resulted. This was particular ly evident in the trial of the Ringer's injection mixture (Fig. 2). Gassing to a p H of 7.40 had a detrimental effect on the ability of the mixture to maintain lens clarity, perhaps by depleting the acidabsorbing capacity of the sodium bicar bonate buffer. Forty-eight hours' incubation—Only the lenses incubated in G-B-R remained clear for 48 hours. G-B-R maintained lens clarity for as long as 96 hours in some lenses. SUMMARY
By in vitro incubation of rhesus mon key lenses at 37°C, we determined that
Fig. 2 (Christiansen and associ ates). Maintenance of lens clarity after 24 hours of incubation at 37°C in different solutions. D5W indicates 5% dextrose in water; N a H C 0 3 , sodium bicarbonate; PSC, posterior subcapsular cataract; and Total indicates clear lenses and lenses with cataracts.
VOL. 82, NO. 4
INTRAOCULAR IRRIGATING SOLUTIONS
solutions superior to intraocular irrigat ing solutions in common clinical use could be prepared by aseptically adding commerically available solutions of dex trose 5% in water and sodium bicarbonate to either Ringer's injection or Ringer's lactate solutions. While not as effective as glutathione-bicarbonate-Ringer's solu tion (G-B-R) in maintaining lens clarity, these mixtures can be prepared easily in the operating room (in contrast to G-B-R)
OPHTHALMIC
597
and may improve surgical results in pro cedures requiring prolonged intraocular irrigation. REFERENCES 1. Edelhauser, H. F., Van Horn, D. L., Hyndiuk, R. A., and Schultz, R. O.: Intraocular irrigating solutions. Their effect on the corneal endothelium. Arch. Qphthalmol. 93:648, 1975. 2. De Berardis, E., Tieri, O., Palzella, A., and Luglio, N.: The chemical composition of the human aqueous humor in normal and pathological condi tions. Exp. Eye Res. 4:179, 1965.
MINIATURE
J. G. Zinn, Descriptio Anatomica Oculi Humant, 1780 Mufculus obliquus inferior
Bethesda, Maryland R O N A L D G. M I C H E L S ,
M.D.
Baltimore, Maryland AND I. M I K U N I , Bethesda,
Surgical techniques such as pars plana vitrectomy may involve prolonged peri ods of intraocular irrigation with large volumes of solution. No commercially available sterile solution has been formu lated specifically for prolonged intra ocular irrigation. The solutions common ly used during vitrectomy are Ringer's injection and Ringer's lactate (chemical composition given in the Table). Intraop erative cataract formation (in cases where lens removal is not indicated) and tran sient postoperative corneal decompen sation indicate that prolonged irrigation with these solutions is damaging to ocular tissues. Edelhauser and associates 1 have re cently developed a glutathione-bicarbonate-Ringer solution (G-B-R) that pro tects corneal endothelial function and ultrastructure during in vitro perfusion studies for up to six hours. To evaluate the effects of G-B-R and other irrigating solutions on lens clarity in vitro, monkey lenses were incubated at 37°C and exam-
From the Clinical Branch (Drs. Christiansen, Kol larits, and Fishman) and the Laboratory of Vision Research (Drs. Fukui and Mikuni), National Eye Institute, National Institutes of Health, Department of Health, Education and Welfare, Bethesda, Mary land, and the Wilmer Eye Institute, Johns Hopkins Hospital (Dr. Michels), Baltimore, Maryland. Reprint requests to Carol Kollarits, M.D., Clinical Branch, National Eye Institute, National Institutes of Health, Bethesda, MD 20014.
M.D.
Maryland
ined for evidence of cataract formation. Our purpose was to find an irrigating solution that could be prepared from commercially available stock solutions in the operating room and would be effec tive in maintaining lens clarity during prolonged intraocular surgery. M A T E R I A L AND M E T H O D S
Lenses were removed from 50 enucleat ed rhesus monkey eyes, taking care to minimize trauma. Isolated lenses were incubated in sterile Petri dishes contain ing 4.0 ml of irrigating solution at 37°C. One of each pair of lenses was incubated in a different solution to serve as a con trol. The Table lists the chemical compo sition of the irrigating solutions with their p H and osmolarity. The G-B-R solution was prepared here. The Ringer's injec tion, Ringer's lactate, 5% dextrose in wa ter, and sodium bicarbonate are commer cially available sterile solutions. A sodi um bicarbonate buffer system and 5.5 mM glucose (dextrose) were present in normal aqueous. 2 By aseptically injecting 18.0 ml of 5% dextrose in water and 20.0 ml of sodium bicarbonate (available as 50 m E q in 50 ml of water) into a standard 1,000-ml intravenous solution bottle of Ringer's injection or Ringer's lactate, so lutions were obtained that approached the glucose and bicarbonate concentra tions of G-B-R without an excessive in crease in osmolarity. The alkaline p H of
594
VOL. 82, NO. 4
INTRAOCULAR IRRIGATING SOLUTIONS
595
TABLE CHEMICAL COMPOSITION O F IRRIGATING SOLUTIONS
Ringer's Injection Solution, mM/1
Ringer's Lactate Solution, mM/1
111.56 4.82 1.04 0.78 0.86 29.20 5.01 0.50 0.30
147.00 4.00 1.00
103.40 4.05 0.60
306 7.40
309 5.80
G-B-R Solution, mM/1 Sodium chloride Potassium chloride Calcium chloride Magnesium chloride Sodium phosphate Sodium bicarbonate Glucose Adenosine Reduced glutathione Sodium lactate Osmolarity (mOsm/1) pH
-
-
-
28.00 273 6.70
D-5-W an d NaHCOa* in Ringer's Ringer's Lactate Injection Solution,f Solution.t mM/1 mM/1 147.00 4.00 1.00
103.40 4.05 0.60
20.00 5.00
20.00 5.00
310 8.03
28.00 278 8.15
-
-
*D-5-W (dextrose 5% in water) and NaHC0 3 (sodium bicarbonate) were added to these solutions. t These solutions can be prepared aseptically in the operating room by injecting 18.0 ml of commençai 5% dextrose in water and 20.0 ml of sodium bicarbonate solution (available in 50-ml ampules containing 50 mEq of sodium bicarbonate) into a 1,000-ml bottle of Ringer's injeclion or Ringer's lactate solution.
these solutions could be lowered to 7.4 by gassing with carbon dioxide but this step was found to be unnecessary. The incubating lenses were examined at four hours, 24 hours, and 48 hours for evidence of cataract formation. We per formed microscopic examination (lOx) of each lens, placing the Petri dish on a dark-background Amsler grid to facilitate detection of opacities. A lens without cortical or posterior opacities was desig nated "clear." A "cloudy" lens showed diffuse cortical haziness. This diffusely opaque cataract was tabulated separately from posterior stellate or leaf-shaped opacities because these leaf-shaped opac ities sometimes cleared spontaneously during further incubation. RESULTS
Four hours' incubation—Incubation of monkey lenses in G-B-R solution at 37°C resulted in 100% maintenance of lens clarity at four hours. No posterior changes were observed. Incubation of the lenses in Ringer's
injection solution resulted in only 10% of the lenses remaining clear at four hours. The addition of 5% dextrose in water as an energy source improved the mainte nance of lens clarity to the 20% level. Addition of the sodium bicarbonate buff er system without 5% dextrose in water increased the level to 40% (Fig. 1). The addition of both 5% dextrose in water and sodium bicarbonate produced a dramatic increase in the ability of Ringer's injec tion solution to maintain lens clarity. Sev enty percent of lenses were clear at four hours, and if lenses with posterior (re versible) changes are included, the level is 90%. Ringer's lactate solution contain ing 5% dextrose in water and sodium bicarbonate was also tested. While the percentage of clear lenses was higher for the Ringer's injection mixture at four hours, inclusion of the posterior lens opacities increases the percentage for the Ringer's lactate mixture. There was no significant difference between the mix ture based on either Ringer's injection or Ringer's lactate solutions at four or 24
596
AMERICAN JOURNAL OF OPHTHALMOLOGY
OCTOBER, 1976
Fig. 1 (Christiansen and associ ates). Maintenance of lens clarity after four hours of incubation at 37°C in different solutions. D5W indicates 5% dextrose in water; N a H C 0 3 , sodium bicarbonate; PSC, posterior subcapsular cataract; and Total indicates clear lenses and lenses with cataracts.
hours of incubation. These mixtures were also gassed with carbon dioxide to a p H of 7.40 without apparent improvement in effectiveness. Twenty-four hours' incubation—At 24 hours, all of the lenses incubated in G-B-R solution remained clear. After 24 hours of incubation, all of the lenses in unsupplemented Ringer's injection and Ringer's lactate solutions were cataractous. The addition of either 5% dextrose in water or sodium bicarbonate did not improve the result. When both 5% dex trose in water and sodium bicarbonate were added to Ringer's injection or Ring er's lactate solutions, a marked increase in the ability of these solutions to maintain
lens clarity resulted. This was particular ly evident in the trial of the Ringer's injection mixture (Fig. 2). Gassing to a p H of 7.40 had a detrimental effect on the ability of the mixture to maintain lens clarity, perhaps by depleting the acidabsorbing capacity of the sodium bicar bonate buffer. Forty-eight hours' incubation—Only the lenses incubated in G-B-R remained clear for 48 hours. G-B-R maintained lens clarity for as long as 96 hours in some lenses. SUMMARY
By in vitro incubation of rhesus mon key lenses at 37°C, we determined that
Fig. 2 (Christiansen and associ ates). Maintenance of lens clarity after 24 hours of incubation at 37°C in different solutions. D5W indicates 5% dextrose in water; N a H C 0 3 , sodium bicarbonate; PSC, posterior subcapsular cataract; and Total indicates clear lenses and lenses with cataracts.
VOL. 82, NO. 4
INTRAOCULAR IRRIGATING SOLUTIONS
solutions superior to intraocular irrigat ing solutions in common clinical use could be prepared by aseptically adding commerically available solutions of dex trose 5% in water and sodium bicarbonate to either Ringer's injection or Ringer's lactate solutions. While not as effective as glutathione-bicarbonate-Ringer's solu tion (G-B-R) in maintaining lens clarity, these mixtures can be prepared easily in the operating room (in contrast to G-B-R)
OPHTHALMIC
597
and may improve surgical results in pro cedures requiring prolonged intraocular irrigation. REFERENCES 1. Edelhauser, H. F., Van Horn, D. L., Hyndiuk, R. A., and Schultz, R. O.: Intraocular irrigating solutions. Their effect on the corneal endothelium. Arch. Qphthalmol. 93:648, 1975. 2. De Berardis, E., Tieri, O., Palzella, A., and Luglio, N.: The chemical composition of the human aqueous humor in normal and pathological condi tions. Exp. Eye Res. 4:179, 1965.
MINIATURE
J. G. Zinn, Descriptio Anatomica Oculi Humant, 1780 Mufculus obliquus inferior