Reduction of Corneal Thickness by Hypertonic Solutions

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<ul><li><p>REDUCTION O F CORNEAL THICKNESS W I T H HYPERTONIC SOLUTIONS </p><p>KEITH GREEN, P H . D . , AND SUSAN DOWNS, B.S. Baltimore, Maryland </p><p>Many types of hypertonic solutions have been used to reduce corneal edema, and several of these have undergone objective evaluation.1 Recently, a new water-soluble polymer solution, ADAPT (Burton, Parsons Company, Inc., Washington, D.C.), was tested in the treatment of dry eye,2 and it was found that not only was the solution effective over long periods of time but that it was preferred by patients over other solutions tested. </p><p>This study was undertaken to evaluate the reduction in corneal thickness caused by ADAPT containing various concentrations of NaCl. </p><p>MATERIALS AND METHODS </p><p>The experiments were carried out with adult albino rabbits (3-4 kg) whose eyes had not previously been used experimentally. All corneas were initially of normal thickness. The rabbits were restrained in canvas bags tied at the neck and usually sat quietly throughout the experiment. One drop of the test solution was instilled into an eye after a base-line thickness was measured. Thickness was then measured at either half-hour or one-hour intervals thereafter. The drop was always placed superiorly at the 12 o'clock position and allowed to flow over the corneal surface. Corneal thickness was measured using a Haag-Streit model 360 slit lamp with a pachometer attachment3; thickness could be </p><p>From the W. K. Kellogg Foundation Laboratories, The Wilmer Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland. This work was supported by Public Health Service Grant EY 00034 and Research Career Development Award K4 EY 46-354 (Dr. Green) from the National Eye Institute. </p><p>Reprint requests to Keith Green, Ph.D., 267 Woods Building, The Wilmer Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205. </p><p>measured to an accuracy of 1 0 and was always measured centrally. </p><p>Several solutions were used in this study. Initially, a preparation of 5% NaCl with 5% gum cellulose and 2% glycerin solution (Burris and Kemp Pharmacy, Baltimore, Maryland) and BP-E Ocular, an experimental agent consisting of 5% NaCl and 5% glycerin in a buffered aqueous emulsive vehicle (prepared from the same formula as EKG-Sol, an electrocardiography electrode cream, by Burton, Parsons and Company, Inc., Washington, D.C.), were compared and related to the data already available on the effectiveness of these agents on human corneal thickness.1 The studies using ADAPT consisted of a comparison of ADAPT alone with ADAPT containing 2% NaCl and ADAPT containing 5% NaCl against 5% NaCl in distilled water. It was shown earlier1 that low concentrations of NaCl are ineffective in reducing corneal thickness; thus, in the present studies, no tests were made using concentrations lower than 2% NaCl. Similarly, we felt that concentrations greater than 5% NaCl could be irritative to the eye. </p><p>RESULTS </p><p>The reduction in corneal thickness is shown for the four sets of experiments in Tables 1-4, where the percentage reduction in corneal thickness is also given. </p><p>Table 1 shows the effect of the Burris and Kemp solution and BP-E Ocular on the thickness of normal rabbit cornea. The Burris and Kemp solution produced a maximum reduction at one hour after instillation, and at four hours the thickness had almost returned to normal. BP-E Ocular, on the other hand, caused at least a 2.5% reduction from 30 min to five hours after instillation. ADAPT alone (Table 2) caused a moderate </p><p>507 </p></li><li><p>S08 AMERICAN JOURNAL OF OPHTHALMOLOGY MARCH, 1973 </p><p>TABLE 1 NORMAL RABBIT CORNEAL THICKNESS (mm) AS A FUNCTION OF TIME AND APPLIED SOLUTION* </p><p>Time </p><p>Burris and Kemp solution N = 5 </p><p>Change in thickness (%) BP-E Ocular </p><p>N = 5 </p><p>Change in thickness (%) </p><p>0 </p><p>.350 .003 </p><p>.350 + </p><p>.003 </p><p>:30 </p><p>.342 .006 </p><p>2.29 .334 + </p><p>.008 4.57 </p><p>1:00 </p><p>.336 .008 </p><p>4.0 .334 </p><p>.007 4.57 </p><p>2:00 </p><p>.342 .006 </p><p>2.29 .340 </p><p>.004 2.86 </p><p>3:00 </p><p>.342 .007 </p><p>2.29 .340 + </p><p>.007 2.86 </p><p>4:00 </p><p>.346 + </p><p>.004 1.14 .338 </p><p>.005 3.43 </p><p>5:00 </p><p>.344 + </p><p>.006 1.71 .340 </p><p>.006 2.86 </p><p>6:00 </p><p>.352 + </p><p>.004 +0.57 </p><p>.346 </p><p>.005 1.14 </p><p>* The change in thickness is always a reduction unless otherwise indicated. The values shown are the meanSEM. </p><p>reduction in thickness during the experimen- DISCUSSION tal time period while with the addition of 2% The reduction in thickness seen with the NaCl the percentage reduction was increased Burris and Kemp solution and BP-E Ocular at least two- to threefold. ADAPT contain- (Table 1) follows the same time course as ing 5% NaCl (Tables 3 and 4) was even that seen in man,1 but the effect in rabbit is more effective than the 2% NaCl. Five per- half that in man. Based upon this relation-cent NaCl in distilled water (Tables 3 and ship the results with ADAPT containing 2% 4) caused little or no reduction in thickness, and 5% NaCl indicate that these solutions The greater effective time of thinning seen should be highly effective in reducing human in Table 4 compared to that in Table 3 with corneal edema. The degree of reduction ADAPT containing 5% NaCl may be re- should be of the order of 20-25% over a lated to a more effective placement of the long time period. Such a reduction would drop despite attempts to make all experi- make this solution as effective as 5% NaCl ments identical. ointment (the most effective agent tested </p><p>TABLE 2 EFFECT OF ADAPT AND ADAPT PLUS 2% NACL ON NORMAL RABBIT CORNEAL THICKNESS (mm) </p><p>Time </p><p>ADAPT+2% NaCl N = 8 </p><p>Change in thickness (%) ADAPT alone </p><p>N = 8 </p><p>Change in thickness (%) </p><p>0 </p><p>.381 + </p><p>.010 </p><p>.381 + </p><p>.010 </p><p>:30 </p><p>.365 </p><p>.009 4.20 .374 </p><p>.009 </p><p>1.84 </p><p>1:00 </p><p>.358 </p><p>.009 6.04 .374 </p><p>+ .008 </p><p>1.84 </p><p>2:00 </p><p>.361 </p><p>.010 5.25 .376 + </p><p>.008 </p><p>1.31 </p><p>3:00 </p><p>.350 </p><p>.008 </p><p>8.14 .370 </p><p>+ .010 </p><p>2.89 </p><p>4:00 </p><p>.348 </p><p>.005 </p><p>8.66 .368 </p><p>.008 </p><p>3.41 </p><p>5:00 </p><p>.349 + </p><p>.009 </p><p>8.39 .366 </p><p>.012 </p><p>3.94 </p><p>6:00* </p><p>.363 + </p><p>.005 n = 4 10.5 .393 </p><p>.003 n = 4 2.96 </p><p>* The six-hour readings were made only on four corneas and the % change in thickness (always a reduction here) is given for these corneas compared to the original thickness of only these corneas. The values given are the mean SEM. </p></li><li><p>VOL. 75, NO. 3 REDUCTION OF CORNEAL THICKNESS 509 </p><p>TABLE 3 EFFECT OF ADAPT PLUS 5% NACL AND 5% NACL IN DISTILLED WATER </p><p>ON NORMAL RABBIT CORNEAL THICKNESS ( m m ) * </p><p>ADAPT+5% NaCl RE N = 4 </p><p>Change in thickness (%) H 2 0+5% NaCl LE </p><p>N = 4 </p><p>Change in thickness (%) </p><p>0 </p><p>.348 </p><p>.005 </p><p>.350 + </p><p>.006 </p><p>:30 </p><p>.323 + </p><p>.005 7.18 .348 </p><p>.005 0.57 </p><p>1:00 </p><p>.310 </p><p>.004 10.92 </p><p>.340 + </p><p>.004 2.86 </p><p>Time </p><p>1:30 </p><p>.315 + </p><p>.010 9.48 .345 + </p><p>.005 1.43 </p><p>2:00 </p><p>.305 + </p><p>.009 12.36 .345 </p><p>+ .003 1.43 </p><p>3:00 </p><p>.310 </p><p>.011 10.92 .345 + </p><p>.006 1.43 </p><p>4:00 </p><p>.325 </p><p>.010 6.61 .350 </p><p>+ .006 0 </p><p>5:00 </p><p>.335 </p><p>.009 3.74 .350 </p><p>+ .004 0 </p><p>: The values given are the mean+SEM. The change in thickness is always a reduction. </p><p>earlier1) for possibly the same length of time. The advantage of the present preparation is that it is in the form of a solution which can be applied as a drop rather than in an ointment form. </p><p>ADAPT alone, when tested on dry eyes, was long-lasting and well tolerated, and, indeed, was preferred over other solutions tested.2 The use of this polymer solution as a wetting agent has been established as due to the retention of the solution on the corneal surface for long periods,2 and thus is confirmed here where the action of the mixture is evident several hours after instillation. </p><p>The results obtained suggest that ADAPT </p><p>containing 5% NaCl may prove to be an effective solution in reducing corneal edema and clinical trials of such a solution appear to be indicated. </p><p>SUMMARY </p><p>Hypertonie solutions inducing a reduction in corneal thickness were tested in rabbits. Some solutions caused a percentage thickness change in rabbit cornea of about half that seen previously in man. Solutions of ADAPT containing either 2 or 5% NaCl were tested in rabbits and these produced corneal thickness reductions of approximately 8 to 10%. Based upon the relation-</p><p>TABLE 4 EFFECT OF ADAPT PLUS 5% NACL AND 5% NaCL IN DISTILLED WATER </p><p>ON NORMAL RABBIT CORNEAL THICKNESS (mm)* </p><p>Time </p><p>ADAPT+5% NaCl N = 4 </p><p>Change in thickness (%) H 20+5%NaCl </p><p>N = 4 </p><p>Change in thickness (%) </p><p>0 </p><p>.360 + </p><p>.004 </p><p>.358 + </p><p>.003 </p><p>:30 </p><p>.343 + </p><p>.003 4.72 .363 </p><p>.003 + 1.40 </p><p>1:30 </p><p>.333 + </p><p>.003 7.50 .365 </p><p>.003 +1.96 </p><p>2:30 </p><p>.328 + </p><p>.005 8.89 .363 </p><p>+ .003 </p><p>+ 1.40 </p><p>3:30 </p><p>.323 + </p><p>.003 10.28 .363 + </p><p>.003 + 1.40 </p><p>4:30 </p><p>.318 + </p><p>.003 11.67 .363 </p><p>+ .003 </p><p>+ 1.40 </p><p>5:30 </p><p>.323 + </p><p>.003 10.28 .363 </p><p>+ .003 </p><p>+ 1.40 </p><p>* The values given are the meanSEM. The change in thickness is always a reduction unless otherwise indicated. </p></li><li><p>510 AMERICAN JOURNAL OF OPHTHALMOLOGY MARCH, 1973 </p><p>ship seen with solutions used in both species, the results indicate that the ADAPT solutions should be highly effective in reducing human cornea! edema. </p><p>REFERENCES </p><p>1. Luxenberg, M. N., and Greek, K. : Reduction </p><p>OPHTHALMIC MINIATURE </p><p>By integrating the internship into the residency, these programs will become closed, for department of medicine will have no choice but to give preference to those who will remain in medicine. The expectation that departments of psychiatry, radiology, neurology, and so forth will be able, by themselves, to arrange for adequate medical experience for their residents is illusory. Simple arithmetic will demonstrate that no department of medicine could take the flood of residents from other services for whom they are now expected to provide this experience. Nor will they want to be burdened with residents not of their own choosing. Consequently, these house officers will be treated as second-class citizens and will be shunted to second-class appointments, most probably in understaffed community hospitals without adequate resident or attending staff. What logic dictates that the outstanding future pathologist, radiologist, or psychiatrist should not get the best possible training in internal medicine that his ability justifies simply because his ultimate career choice is other than internal medicine? The crucial period, the fourth year of medical school and the internship, during which most physicians have the experiences that enable them to reach some kind of a rational judgment as to the area of medicine for which they are best suited, now is threatened. This is short-sighted and foolhardy to an extreme, for it is in his formative period of youth that the physician should enjoy the greatest options and freedom to make career decisions. Unhappy or unwise career choices can have profoundly unfortunate consequences for patients, not to mention the physician himself. </p><p>George L. Engel Ann. Int. Med. </p><p>76:489, 1972 </p><p>of corneal edema with topical hypertonic agents. Am. J. Ophth. 71:847, 1971. </p><p>2. Barsam, P. C, Sampson, W. G., and Feldman, G. L.: Treatment of dry eye and related problems. Ann. Ophth. 4:122, 1972. </p><p>3. Maurice, D. M., and Giardini, A. A. : A simple optical apparatus for measuring the corneal thickness, and the average thickness of the human cornea. Brit. J. Ophth. 35:169, 1951. </p></li></ul>