INVESTIGATIVE OPHTHALMOLOGY. Dexamethasone testing in Southwestern Indians

Transcription

1 May 1970 Vlume 9, Number 5 INVESTIGATIVE OPHTHALMOLOGY Dexamethasne testing in Suthwestern Luis J. Rsenbaum, Ellen Altn, and Bernard Becker f the Suthwestern United States demnstrated prevalences f primary pen-angle glaucma and respnsiveness t tpical dexamethasne which were cmparable t nnlndian St. Luis ppulatins. In bth ppulatins plasma crtisl suppressin by ral dexamethasne was decreased in individuals in the grup mst respnsive t tpical dexamethasne. demnstrated very high prevalences f phenylthiurea tasters and psitive ral glucse tlerance tests but, cntrary t the St. Luis ppulatins, these tiu parameters did nt crrelate with the tpical dexamethasne respnse. Key wrds: dexamethasne, Nrth American Indian, intracular pressure increase, phenylthiurea taste test, glucse tlerance test, lcal drug administratin, hydrcrtisne, pen-angle glaucma. -Lriinary pen-angle glaucma has been reprted t ccur rarely in f the Suthwestern United States. 1 In additin, phenylthiurea nntasters were fund t be cmmn amng patients with primary pen-angle glaucma, 2 but were reprted t be extremely rare in. 3 Hwever, an impressive number f patients with primary pen-angle glaucma have been seen in the Eye Clinic f the Phenix Indian This investigatin was supprted by grants EY00004 and EY00336 frm the Natinal Eye Institute, Natinal Institutes f Health, Bethesda, Md. Frm the Department f Ophthalmlgy and the Oscar Jhnsn Institute, Washingtn University Schl f Medicine, St. Luis, M. Presented in part at the meeting f the Mississippi Sectin f the Assciatin fr Research in Ophthalmlgy, Denver, Cl., March, Manuscript submitted Sept. 26, 1969; revised manuscript accepted Feb. 16, Hspital. Furthermre, diabetes mellitus has been reprted t be especially frequent in Indian ppulatins.' 1 " 0 Since there is an increased prevalence f respnse t tpical crticsterids in diabetic patients as well as in patients with primary penangle glaucma, 7 " 10 we evaluated tpical crticsterid testing in a grup f Indian vlunteers. Methd Patient selectin. All patients had been hspitalized at Oshrin Hspital fr treatment f tuberculsis and were n therapy fr at least 2 weeks prir t the study. In such a "captive ppulatin," medicatins culd be administered reliably by nurses. Tpical crticsterid testing. The unselected hspitalized vlunteers ranged in age frm the third t the ninth decade (Fig. 1). They came frm 11 different tribes, but mst were Papag r Apache. All had base-line examinatins which included visual acuity, manifest refractin, external examinatin (especially fr trachma), pupillary and mtility examinatins, phthalms-

2 326 Rsenbaum, Altn, and Becker Investigative Ophthalmlgy May NO TUCSON INDIANS AGE (Years) Fig. 1. Age distributin f Indian ppulatin studied cpy fr evaluatin f the ptic disc and diabetic retinpathy, slit lamp examinatin, applanatin tnmetry, tngraphy, and gniscpy. Dexamethasne, * 0.1 per cent phthalmic slutin, was instilled int ne eye 4 times a day fr 6 weeks by a registered nurse. Intracular pressure was checked weekly, and the entire examinatin was repeated at the end f 6 weeks. Plasma crtisl suppressin test. Fasting bld was drawn int heparinized tubes at 8 A.M. fr base-line plasma crtisl values. At 11 P.M., 1 mg. f dexamethasne was given rally, and fasting bld was btained at 8 A.M. the fllwing mrning fr plasma crtisl levels. Plasma crtisl was measured by the methd f Mattingly. 11 Oral glucse tlerance test. Fasting bld, fr glucse was btained. A 75 Gm. lad f glucse was given rally, and Yz, 1 hur, and 2 hur bld specimens were drawn. Patients wh demnstrated diabetic curves had repeat tests. Phenylthiurea taste testing. Slutins f phenylthiurea were prepared in the manner described by Harris and Kalmus, 12 and administered as described by Becker and Mrtn. 2 Patients wh failed t taste 8 mg. per cent were cnsidered nntasters. Results Intracular pressure respnse t tpical dexamethasne. The intracular pressure "Supplied thrugh the curtesy f Dr. Adlph W. Vgel, Merck, Sharp and Dhme Research Labratries, West Pint, Pa ki 14 Q: 10 I>> 6 Tpical Dexamethasne: Befre After (Oppsite Eye ) " INTRAOCULAR PRESSURE(mmHg) Fig. 2. Intracular pressure befre and after 6 weeks f tpical dexamethasne 0.1 per cent fur times daily t ppsite eye. in cntrl eyes presented a nrmal distributin curve prir t and fllwing tpical dexamethasne administered t the ppsite eye (Fig. 2). The experimental eyes, which als behaved as a single ppulatin prir t tpical dexametha-

3 Vlume 9 Number 5 Dexamethasne testing in Suthwestern 327 Tpical Dexamethasne. Befre % After (6 weeks) INTRAOCULAR PRESSURE (mmhg) Fig. 3. Intracular pressure befre and after 6 weeks f tpical dexamethasne 0.1 per cent fur times daily t test eye. b 5 U : ; / / i t i i i 5 - / / / / Tpical Dexamethasne: Befre After (6weeks) INTRAOCULAR PRESSURE (mmhg) Fig. 4. Cumulative frequency plt f intracular pressure in experimental eye befre and after 6 weeks f tpical dexamethasne 0.1 per cent fur times daily. Nte single ppulatin befre and mre than ne ppulatin after 6 weeks.

4 328 Rsenbaum, Altn, and Becker Investigative Ophthalmlgy May 1970 sne, appeared t be distributed as 3 ppulatins fllwing 6 weeks f tpical dexamethasne. The ppulatins culd be separated int pr respnders (intracular pressure rse t less than 23 mm. Hg), intermediate respnders (23 t 33 mm. Hg), and high respnders (greater than 33 mm. Hg) (Figs. 3 and 4). By these criteria, there were 27 (57 per cent) pr respnders, 15 (32 per cent) intermediate respnders, and 5 (11 per cent) high respnders. Fr direct cmparisn with intracular pressure values used in prir studies n St. Luis ppulatins, 23 patients (49 per cent) had intracular pressure rises t less than 20 mm. Hg (nn grup), 17 (36 per cent) rse t 20 t 31 mm. Hg (ng grup), and 7 (15 per cent) rse t greater than 31 mm. Hg (gg grup) after 6 weeks f tpical dexamethasne (Table I). Plasma crtisl suppressin. The mean suppressin rati (plasma crtisl 24 hurs /plasma crtisl 0 hurs) fllwing 1 mg. f ral dexamethasne fr the nn grup was 20 per cent f base line with a standard deviatin f 10 per cent (Fig. 5). There was n significant difference between the 23 patients whse intracular pressure rse t less than 20 and the 27 whse intracular pressure rse t less than 23 mm. Hg. There were 7 patients wh had plasma crtisl levels greater than 40 per cent f their base-line value. Nne f these were classified as lw respnders, 3 were intermediate respnders, and 4 were high respnders t tpical dexamethasne. Thus in the gg grup, 4 (57 per cent) f 7 and in the ng grup 3 (17 per cent) f 17 had ratis greater than 40 per cent (Table II). Glucse tlerance. A plasma glucse level greater than 160 mg. per cent tw hurs after 75 Gm. f ral glucse was cnsidered psitive. On this basis, 22 patients had psitive glucse tlerance tests. 0 These were classified as 11 nn, 7 ng, and 4 gg individuals (Table III and IV). In cntrast t the St. Luis ppulatins, diabetic and nndiabetic demn- Table I. Tucsn Indian study; tpical dexamethasne test St. Luis vlunteers S24 S N H"- 0 <20mmHg Applanatin pressure (mm. Hg) after sterids (6 weeks) < > < > f mmHg >31 mmhg Fig. 5. Cmparisn f suppressin ratis (plasma crtisl 24 hurs/plasma crtisl 0 hurs) fllwing ral dexamethasne (1 mg.) in nn, ng, and gg ppulatins. strated n significant difference in respnse t tpical crticsterids. Only ne patient had nnprliferative diabetic retinpathy and he was in the nn grup. Phenylthiurea taste test. There were n nntasters amng the 47 tested (Table V). Other bservatins. There were n changes in visual acuity greater than ne line n the Snellen chart. N ptsis r mydriasis was nted fllwing administratin f tpical sterids. There were 22 patients with Stage IV trachma but n evidence f activatin f the disease while n tpical sterids.

5 c t t c c t Vlume 9 Number 5 Dexamethasne testing in Suthwestern 329 Table II. Tucsn Indian study; crtisl suppressin nn S w /S 0 St. Luis SM/SO > 40% 0/22 (0%) > 65%* 1/40 (3%) Tw standard deviatins frm mean in nn ppulatin. Grup ng 3/17 (18%) 3/54 (6%) tm 4/7 (57%) 16/54 (30%) Table III. Tucsn Indian study; diabetes and tpical crticsterid test Indian diabetics Indian nndiabetics St. Luis diabetics St. Luis nndiabetics N Applanatin pressure (mm. Hg) after sterids (6 weeks) < Table IV. Tucsn Indian study psitive glucse tlerance* 11/23 (48%) 7/17 (41%) 4/7 (57%) Ttal 22/47 (47%) (63% ver 40 yr.) Tvv hur > 160 nig. per cent St. Luis 1/34 (3%) 2/38 (5%) 17/97 (17%) Table V. Tucsn Indian study; phenylthiurea taste test (per cent nntasters) ng St. Luis (Caucasian) Discussin It appears that f the Suthwestern United States have the same r slightly greater gene prevalence fr pressure respnsiveness t tpical crticsterids as d nnlndian ppulatins (Table I). The small differences between the St. Luis vlunteers and the is nt significant. Althugh high respnsiveness t tpical dexamethasne testing and primary pen-angle glaucma may nt be identical, they are certainly clsely related It is therefre f interest t nte that a review f adult Indian utpatient visits t the eye clinic f the Phenix Indian Hspital shws the incidence f penangle glaucma t be apprximately that fund in a nnlndian ppulatin. 14 As fund by Levene and Schwartz 15 and cnfirmed by Becker and Ramsey, 10 a negative crrelatin exists between the rise in intracular pressure fllwing tpical sterids and the suppressin f plasma crtisl by ral dexamethasne. This is als fund in an Indian ppulatin (Table II). Many authrs have reprted a higher prevalence f increased intracular pressure in diabetic patients. 7 ' 0> 17 ' 19 In additin, Becker and assciates 9 fund mre high and intermediate respnders t tpical sterids amng diabetic patients than in a nndiabetic (nnlndian) vlunteer ppulatin. Cnversely, Armaly and Balglu 20 claim that diabetic adults have a decreased intracular pressure at varius ages and that diabetic patients have n greater frequency f cular hypertensin than cntrl subjects. Hwever Armaly 21 des find a greater frequency f respnders t tpical crticsterids in Caucasian juvenile diabetic patients. Indian diabetic patients d nt shw a higher prevalence f respnsiveness t tpical crticsterid testing than d Indian nndiabetics. This

6 330 Rsenhaum, Altn, and Becker Investigative Ophthalmlgy May 1970 is in marked cntrast t nnlndian St. Luis ppulatins (Table III). In nnlndians there is a significantly greater prevalence f psitive ral glucse tlerance tests in the gg respnders than in nn and ng ppulatins. 22 ' 23 Hwever, tested in this study shw n significant relatinship between respnsiveness t tpical sterid testing and ral glucse tlerance testing (Table IV). Anther genetic marker which relates t primary pen-angle glaucma is the inability t taste phenlythiurea. Becker and Mrtn 2 fund 53 per cent nntasters in Caucasians with primary pen-angle glaucma as cmpared with 28 per cent nntasters in nnglaucmatus Caucasians. Thirty-seven per cent f St. Luis Negres with primary pen-angle glaucma were nntasters, while nly 17 per cent f nnglaucmatus Negres were s classified. Hwever, appear t shw n crrelatin between phenylthiurea taste testing and tpical sterid respnsiveness (Table V). REFERENCES 1. Thygesn, P., and Dawsn, C. R.: Ophthalmlgical prblems f the American Indian, Trans. Pacif. Cast Ot-Ophthal. Sc, 1959, p Becker, B., and Mrtn, W. R.: Phenylthiurea taste testing and glaucma, Arch. Ophthal. 72: 323, MacRberts, M. H.: Taste sensitivity t phenylthicarbamide (PTC) amng the Papag f Arizna, Hum. Bil. 36:28, Jhnsn, J. E., and McNatt, C. W.: Diabetes mellitus in an American Indian ppulatin islate, Texas Rep. Bil. Med. 22: 110, Saiki, J. H., and Rimin, D. C: Diabetes mellitus amng the Navaj. I. Clinical features, Arch. Int. Med. 122: 1, Miller, M., Bennett, P., and Burch, T.: Hyperglycemia in Pima : A preliminary appraisal f its significance, bimedical challenges presented by the American Indian, Pan American Health Organizatin, Washingtn, D. C, 165: 89, Hetheringtn, J., and Shaffer. R. N.: Glaucma Research Cnference, Amer. J. Ophthal. 58: 1065, Becker, B.: Intracular pressure respnse t tpical crticsterids, INVEST. OPHTHAL. 4: 198, Becker, B., Bresnick, C, Chevrette, L., Klker, A. E., Oaks, M., and Cibis, A.: Intracular pressure and its respnse t tpical crticsterids in diabetics, Arch. Ophthal. 76: 477, Becker, B., and Hahn, K.: Tpical crticsterids and heredity in primary pen-angle glaucma, Amer. J. Ophthal. 57: 543, Mattingly, D.: A simple flurimetric methd fr the estimatin f free 11-hydrxycrticids in human plasma, J. Clin. Path. 15: 374, Harris, H., and Kalmus, H.: Measurement f taste sensitivity t phenylthiurea, Amer. J. Eugen. 15: 24, Armaly, M. F.: Inheritance f dexamethasne hypertensin and glaucma, Arch. Ophthal. 77: 747, Hshiwra, F., and Rsenbaum, L. J.: Unpublished data. 15. Levene, R. Z., and Schwartz, B.: Depressin f plasma crtisl and the sterid cular pressure respnse, Arch. Ophthal. 80: 461, Becker, B., and Ramsey, C. K.: Plasma crtisl and the intracular pressure respnse t tpical crticsterids, Amer. J. Ophthal. (In press.) 17. Armstrng, J. R., Daily, R. K., Dbsn, H. L., and Girard, L. J.: The incidence f glaucma in diabetes mellitus, Amer. J. Ophthal. 55: 55, Christianssn, J.: Intracular pressure in diabetes mellitus, Acta Ophthal. 39: 155, Safir, A., Paulsen, E. P., and Klayman, J.: Elevated intracular pressure in diabetic children, Diabetes 13: 161, Armaly, M. F., and Balglu, P. J.: Diabetes mellitus and the eye. II. Intracular pressure and aqueus humr utflw facility, Arch. Ophthal. 77: 493, Armaly, M. F.: Tpical dexamethasne and intracular pressure, in Leydhecker, editr: Glaucma sympsium, Basel, 1967, S. Karger, pp Armaly, M. F.: Dexamethasne cular hypertensin and esinpenia, and glucse tlerance test, Arch. Ophthal. 78: 193, Becker, B.: Recent endcrine studies in glaucma, Prctr Lecture, San Francisc, Dec, T be published.