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Toxic Effect of Fluorouracil on the Rabbit Retina: Reply
398
AMERICAN JOURNAL OF OPHTHALMOLOGY
sensitive to a thimerosal preparation than to a preparation without thimerosal. In reviewing the types of soft contact lenses our patients were wearing we found that most were fitted with ultrathin lenses of 0.06 to 0.07 mm in central thickness. All the popular brands have been incriminated with producing giant papillary conjunctivitis. We have had little experience fitting and following patients with the Bausch and Lomb series of lenses. We did find that one particular brand of lenses had a higher incidence of giant papillary conjunctivitis than other brands. However, this brand is frequently prescribed in our area by non-ophthalmologists. Additionally, this group of patients appeared to have higher incidence of poor-fitting lenses and poor regard for cleaning their lenses. Thus the question is raised that if the incidence of giant papillary conjunctivitis is the same for all contact lens wearers but there is one brand or type of lens that is dispensed with a significantly greater frequency than others, the absolute number of patients would be greater with this particular brand than other brands. This sampling bias can often lead to erroneous clinical impressions. In summary, we thought the thimerosal allergic reaction was not present in any of our patients. We were not impressed with any significant difference in the tear immunoglobulins between patients using chemical disinfectants as compared to heat or in patients using thimerosal saline as compared to Unisol saline. While lens design most probably will be found to playa role in the cause of giant papillary conjunctivitis, at present we do not think we have enough evidence to state that lens thinness per se is a significant factor.
MARCH,1984
Because of the many different lenses, different methods of sterilization, different types of lens care routines, and different wearing habits, the number of variables to be considered are large and make it difficult to formulate clinical impressions as to etiologic factors without carefully controlled studies. PETER C. DONSHIK, M.D. MARK BALLOW, M. D. Farmington, Connecticut
Toxic Effect of Fluorouracil on the Rabbit Retina EDITOR:
In the article, "Toxic effect of fluorouracil on the rabbit retina" (Am. J. Ophthalmol. 96:641, Nov. 1983), by N. Nao-i and Y. Honda, the Material and Methods section does not describe how much fluorouracil was used in the perfusate and for how long. There is no discussion about the size of the various subgroups and no information about control experiments. Figure 1 does not show the electroretinographic b-wave amplitudes of controls. (The reader is forced to extrapolate the experimental design from the Results section.) I am also not sure whether extrapolations from an in vitro experiment can be made regarding the absolute numbers of fluorouracil. ROBERT MACHEMER, M. D. Durham, North Carolina
Reply EDITOR:
The technique on in vitro retina we used was established about 15 years ago
VOL. 97, NO. 3
CORRESPONDENCE
and it has been routinely used in many electrophysiologic studies. Our earlier publications'P are related to our reference number 1 in the text. We mixed fluorouracil in the control medium at several concentrations that remained constant throughout the experiments until washout procedures. This technique of drug administration has been routinely employed in in vitro studies. We substituted a concentration of 10-7 g/ml, because there are minimal differences at concentrations less than 10-5 g/ml. Fluorouracil in these concentrations was completely dissolved in the control medium. Increased osmotic pressure and change of pH were negligible. There is no doubt that the b-wave suppression observed by the administration of concentrations of fluorouracil of 10-4 g/ml or greater was the result of fluorouracil. From these animal experiments in vitro, we do not conclude that fluorouracil is dangerous to human retina. We believe that the safety of fluorouracil must be determined before routine clinical use. Our experimental data suggest a possibility of the toxic effect of this chemical. Our study on the toxicity of fluorouracil on in vivo rabbit eyes is now in . progress. Thus far we have observe~ the toxicity to in vivo retina to be SImIlar to that to in vitro retina. NOBUHISA NAO-I, M.D. YOSHIHITO HONDA, M.D. Kyoto, Japan
399
Effect on the Retina of an Air Cushion in the Anterior Chamber and Coaxial illumination EDITOR:
In their article, "Effect on the retina of an air cushion in the anterior chamber and coaxial illumination" (Am. J. Ophthalmol. 96:600, Nov. 1983), P. U. Fechner and R. Barth stated that the danger of light-induced maculopathy is considerably reduced but not eliminated if an intraocular lens is implanted with its plano surface forward. For the last year I have done all procedures in cataract surgery except anterior capsulotomy, cortical clean up, and posterior capsule polishing by using only head illumination, and not coaxial light. The only reason a microscope is needed for suturing with 10-0 nylon suture is for magnification, not for the excessive illumination provided by coaxial lighting. Many microscopes are equipped with side lighting which should have no effect on the macula. However, just the illumination from an overhead operating light is more than sufficient to perform precise suturing even with small sutures. With this in mind, it seems that the best way to avoid light-induced maculopathy would be to use an intraocular lens with the plano surface forward to achieve the benefits noted by Drs. Fechner and Barth, but also, and more importantly, to perform every step possible without coaxial light. D. KING AYMOND, M. D. Sheboygan, Wisconsin
REFERENCES 1. Honda, Y.: Rhythmic wavelets recorded fro~ an in vitro preparation of mammalian retina. Experimentia 25:551, 1969. 2. Honda, Y.: Quantitative analysis of some effects of ouabain upon the electrical activity of mammalian retinas. Invest. Ophthalmol. Vis. Sci. 11:699, 1972.
Reply EDITOR:
With our article we desired to contribute to the realization by our profes-
AMERICAN JOURNAL OF OPHTHALMOLOGY
sensitive to a thimerosal preparation than to a preparation without thimerosal. In reviewing the types of soft contact lenses our patients were wearing we found that most were fitted with ultrathin lenses of 0.06 to 0.07 mm in central thickness. All the popular brands have been incriminated with producing giant papillary conjunctivitis. We have had little experience fitting and following patients with the Bausch and Lomb series of lenses. We did find that one particular brand of lenses had a higher incidence of giant papillary conjunctivitis than other brands. However, this brand is frequently prescribed in our area by non-ophthalmologists. Additionally, this group of patients appeared to have higher incidence of poor-fitting lenses and poor regard for cleaning their lenses. Thus the question is raised that if the incidence of giant papillary conjunctivitis is the same for all contact lens wearers but there is one brand or type of lens that is dispensed with a significantly greater frequency than others, the absolute number of patients would be greater with this particular brand than other brands. This sampling bias can often lead to erroneous clinical impressions. In summary, we thought the thimerosal allergic reaction was not present in any of our patients. We were not impressed with any significant difference in the tear immunoglobulins between patients using chemical disinfectants as compared to heat or in patients using thimerosal saline as compared to Unisol saline. While lens design most probably will be found to playa role in the cause of giant papillary conjunctivitis, at present we do not think we have enough evidence to state that lens thinness per se is a significant factor.
MARCH,1984
Because of the many different lenses, different methods of sterilization, different types of lens care routines, and different wearing habits, the number of variables to be considered are large and make it difficult to formulate clinical impressions as to etiologic factors without carefully controlled studies. PETER C. DONSHIK, M.D. MARK BALLOW, M. D. Farmington, Connecticut
Toxic Effect of Fluorouracil on the Rabbit Retina EDITOR:
In the article, "Toxic effect of fluorouracil on the rabbit retina" (Am. J. Ophthalmol. 96:641, Nov. 1983), by N. Nao-i and Y. Honda, the Material and Methods section does not describe how much fluorouracil was used in the perfusate and for how long. There is no discussion about the size of the various subgroups and no information about control experiments. Figure 1 does not show the electroretinographic b-wave amplitudes of controls. (The reader is forced to extrapolate the experimental design from the Results section.) I am also not sure whether extrapolations from an in vitro experiment can be made regarding the absolute numbers of fluorouracil. ROBERT MACHEMER, M. D. Durham, North Carolina
Reply EDITOR:
The technique on in vitro retina we used was established about 15 years ago
VOL. 97, NO. 3
CORRESPONDENCE
and it has been routinely used in many electrophysiologic studies. Our earlier publications'P are related to our reference number 1 in the text. We mixed fluorouracil in the control medium at several concentrations that remained constant throughout the experiments until washout procedures. This technique of drug administration has been routinely employed in in vitro studies. We substituted a concentration of 10-7 g/ml, because there are minimal differences at concentrations less than 10-5 g/ml. Fluorouracil in these concentrations was completely dissolved in the control medium. Increased osmotic pressure and change of pH were negligible. There is no doubt that the b-wave suppression observed by the administration of concentrations of fluorouracil of 10-4 g/ml or greater was the result of fluorouracil. From these animal experiments in vitro, we do not conclude that fluorouracil is dangerous to human retina. We believe that the safety of fluorouracil must be determined before routine clinical use. Our experimental data suggest a possibility of the toxic effect of this chemical. Our study on the toxicity of fluorouracil on in vivo rabbit eyes is now in . progress. Thus far we have observe~ the toxicity to in vivo retina to be SImIlar to that to in vitro retina. NOBUHISA NAO-I, M.D. YOSHIHITO HONDA, M.D. Kyoto, Japan
399
Effect on the Retina of an Air Cushion in the Anterior Chamber and Coaxial illumination EDITOR:
In their article, "Effect on the retina of an air cushion in the anterior chamber and coaxial illumination" (Am. J. Ophthalmol. 96:600, Nov. 1983), P. U. Fechner and R. Barth stated that the danger of light-induced maculopathy is considerably reduced but not eliminated if an intraocular lens is implanted with its plano surface forward. For the last year I have done all procedures in cataract surgery except anterior capsulotomy, cortical clean up, and posterior capsule polishing by using only head illumination, and not coaxial light. The only reason a microscope is needed for suturing with 10-0 nylon suture is for magnification, not for the excessive illumination provided by coaxial lighting. Many microscopes are equipped with side lighting which should have no effect on the macula. However, just the illumination from an overhead operating light is more than sufficient to perform precise suturing even with small sutures. With this in mind, it seems that the best way to avoid light-induced maculopathy would be to use an intraocular lens with the plano surface forward to achieve the benefits noted by Drs. Fechner and Barth, but also, and more importantly, to perform every step possible without coaxial light. D. KING AYMOND, M. D. Sheboygan, Wisconsin
REFERENCES 1. Honda, Y.: Rhythmic wavelets recorded fro~ an in vitro preparation of mammalian retina. Experimentia 25:551, 1969. 2. Honda, Y.: Quantitative analysis of some effects of ouabain upon the electrical activity of mammalian retinas. Invest. Ophthalmol. Vis. Sci. 11:699, 1972.
Reply EDITOR:
With our article we desired to contribute to the realization by our profes-