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The         Cup/Disc Ratio
    The Findings of Tonometry and
    Tonography in the Normal Eye
     Mansour F. Armaly, MD, and
     Roger E. Sayegh, MD, Iowa City
                                                           ied directly and significantly as that of their
                                                           parents;   similar relationship was seen
                                                           among siblings. There was no significant
                                                           age effect on this ratio. Gross inspection of
                                                           the data failed to show significant relation¬
                                                           ship between appianation pressure ( )
                                                           level and the magnitude of this ratio.
                                                              In another report2 it was suggested that
                                                           enlargement of the optic cup may be the
       In eyes with normal fields, the cup/disc (C/D)      first ocular evidence of the damaging effect
    ratio was found to be significantly related to ap-     of increased ocular pressure. The question
    planation pressure PA level, ratio of pressure read-   arose as to whether in the normal eye varia¬
    ing at the beginning of the tonogram and the           tion in the cup/disc (C/D) ratio is related
    tonographic estimate of aqueous outflow activity       to variation in ocular pressure level. This
    (Po/C), and C-value. The frequency of C/D > 0.3
    increased significantly with the PA level and with     is especially interesting since each of the
    the magnitude of the Po/C ratio. It increased also     two parameters was shown to be genetically
    as the C-value became smaller. This relationship       determined and to be in all likelihood con¬
    was independent of age or family history of            trolled by multifactorial inheritance. Of
    glaucoma.                                              equal interest is the possible relationship
                                                           between the C/D ratio and the tonographic
                                                           estimate of aqueous outflow activity (C)
     1  HE RATIO between the diameter of the               and the pressure reading at the beginning of
    optic cup and that of the optic disc in the            the tonogram (P0)/C in the normal eye.
    normal eye of first degree relatives demon¬              An appropriate sample was studied to
    strated relationships indicative of its genetic        evaluate the above questions. Its results un¬
    determination.1 The ratio in offspring var-            covered a statistically significant relation¬
      Submitted for publication April 6, 1969.             ship between the C/D ratio on the one hand
      From the Department of Ophthalmology, University     and ocular pressure, C-value, and P0/C
    Hospitals, Iowa City.                                  ratio on the other. In normal eyes the fre¬
      Reprint requests to the Department of Ophthalmol-
    ogy, University Hospitals, Iowa City 52240 (Dr.        quency of C/D ratio > 0.3 varied signifi¬
    Armaly).                                               cantly with variation in the above mea-

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Fig    1.—Effect of   PA reading   on   distribution of   C/D     Fig 2.—Effect of age on C/D ratio, with two age
         ratio, with two groups of readings: PA < 20 mm Hg                 group readings: < 40 years (light striation) and > 39
         (light stippling) and PA == 20 mm Hg (dark stippling).            years (dark striation).
         sures.        It increased markedly as the
         increased,       as the P„/C ratio became greater,                    Fig 3.—Effect of PA on C/D in younger age groups,
         and     as   the C-value became smaller.                          with two groups of PA readings:        < 20 mm Hg
                                                                           (light stippling) and PA < 20 mm Hg (dark stippling).
                                 The Sample
           The sample was limited to 1,444 subjects
         in whom ophthalmoscopic examination of
         the C/D ratio was performed by a single
         examiner (R.S.). They fulfilled the follow¬
         ing requirements:
            1. Absence of ocular complaint and of
               history or evidence of past ocular dis¬
                  ease,   injury,   or   surgery.
            2. Visual acuity of 20/25 or better in
               each eye.
            3. Distance refraction not exceeding 3
               diopters of myopia or 1.5 D of astigma¬
               tism.
            4. Normal visual field examination of
               each eye using the Goldmann perim¬                                  was   performed without dilating the pupil,
               eter with the I-2-e.                                                except  on rare occasions when it was felt

            5. Reliable and satisfactory performance                               that estimation of the ratio could not be
               on Goldmann perimetry, applanation                                  reliably made in the undilated pupil.
                                                                                   This ratio was recorded separately for
               tonometry, and tonography.                                          each eye.
                                    Procedure                                4. Applanation tonometry and tonography
                                                                                were then performed by an independent
            The sequence of testing was as follows:                             research technician who was completely
            1. Determination of best corrected visual                           unaware of the estimated C/D ratio.
               acuity for distance using Snellen-type                        In all cases the C/D ratio was recorded prior
               chart.                                                      to and without any knowledge of the result of
            2. Goldmann perimetry using the I-2-e stim¬                    tonometry and tonography. All tests were com¬
               ulus.                                                       pleted on the same day.
            3. Ophthalmoscopy to rule out gross abnor¬
               mality to the posterior pole and to esti¬                                           Results
               mate the ratio of the horizontal diameter
               of the optic cup to that of the optic disc                    The distribution of the C/D ratio in the
               and record it to the nearest tenth. This                    normal eye was shown to differ significantly


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Fig 5.—Effect of P, on C/D ratio, with percentage
                                                            frequency of C/D = 0.00-0.3, inclusive, in light stip¬
                                                            pling and that of C/D > 0.3 in dark stippling.
      Fig 4.—Effect of PA on C/D in older age group, with
   two groups of   PA readings: PA < 20 mm Hg (light
   stippling) and PA > 20 mm Hg (dark stippling).




     Fig 6.—Effect of C-value on C/D ratio, with per¬          Fig 7.—Effect of P„/C on C/D ratio, with percentage
   centage frequency of C/D = 0.00-0.3 in light stippling   frequency of C/D = 0.00-0.03 in light stippling and
   and that of   C/D > 0.3   in dark   stippling.           that of C/D > 0.3 in dark stippling.


   from the      gaussian statistical distribution.1        C/D values occurred          more    frequently in
   The   same was     true for the distributions of         eyes   with      > 19 than in those with
   PA, C,  and ,,/C.3"5 Therefore, in the analy¬            PA  < 20. An appropriate boundary for this
   ses that follow, the chi-square test will be used        trend seems to be at C/D ratio of 0.3. To
   to evaluate the statistical significance of a            evaluate this trend statistically, C/D ratios
   difference in frequency of certain observa¬              were divided into two subgroups: One in¬
   tions.                                                   cluded C/D values of 0 to 0.3 inclusive, and
      Applanation Pressure and C/D Ratio.—                  the other included C/D values > 0.3. The
   The sample was divided into two groups                   percentage of eyes falling into each sub¬
   depending upon the PA readings: the first                group of C/D values was calculated in each
   included eyes with a PA < 20 mm Hg and                   PA group. In eyes with lower PA readings
   consisted of 2,467 eyes, and the second in¬               (PA < 20 mm Hg) 15.5% had a C/D ratio
   cluded those with          > 19 mm Hg and                 > 0.3; whereas in eyes with higher PA read¬
   consisted of 421 eyes. The frequency distri¬             ings (PA > 20 mm Hg) 23.3% had a C/D
   bution of the C/D ratio in each group ap¬                ratio > 0.3. This increase in frequency is
   pears in Fig 1. The frequency was expressed              statistically highly significant at the 1%
   in percentage instead of absolute number to              level of confidence using the chi-square test.
   permit visual comparison of the two groups.                 In the group with high PA readings, one
   It is obvious that small C/D values oc¬                  expects to find older individuals to predomi¬
   curred less frequently in eyes with PA > 19              nate because of the increase in PA with age
   than in those with PA < 20; similarly large              in the normal eye.3 One might argue that if


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age alone had      a   similar association with       Table   1.—Percentage Frequency of CID > 0.3 ¡
                                                                           Different PA, C, and P0/C Values
          large C/D ratios then the results of the
          preceding analysis may reflect that effect                                          Total     Frequency of C/D >
          rather than an effect of PA level. In a                                              No.           0.3 in %

          preceding study no age effect could be un¬              Pa in mm    Hg
          covered on the C/D ratio. The distribution                <16                      1,432              12.8
                                                                      16-19                  1,036              19.4
           of C/D ratios in children did not differ                   20-23                       307           23.3
          from that of their adult parents. However,                >24                           115           35.7
           because of the significance of this uncertain¬         C-value in µ /mm Hg/min
                                                                                                  194           11.8
                                                                    >0.30
          ty it became important to rule out such                     0.25-0.34                   868           12.3
          association between age and C/D ratio in                    0.15-0.24              1,136              16.9
                                                                    <0.15                         686           23.2
          this present sample. The sample was di¬
          vided into two age groups: One included                 P0/C Ratio
                                                                     0-99                    2,216              14.5
          those whose age was < 40 years and the                     100-150                      474           20.0
                                                                    >150                          194           32.1
          other included those whose age was > 39
          years. The first consisted of 690 eyes and the
          second included 2,198. The median age for              Table 2.—Percentage Frequency of Limit Values of
          the first was 31 years and for the second it                 Pa, C, and Z,. in Different C/D Ratios
          was 59 years. The percentage frequency dis¬                                         Percentage Frequency
          tribution of C/D ratio in each age group ap¬                C/D          Total   .-'-.
                                                                     Ratio          No.     Pa>19       C<0.15 Zp>2.00
          pears in Fig 2. There is a suggestion that in
          the older age group the frequency of large                0.0-0.2        1,822    13            9.7       4.17
                                                                    0.3-0.5         952     15.1         11.2       5.25
          C/D ratios may be greater. In the younger                 0.6-0.8         114     29           37.7      17.69
          age group, C/D > 0.3 occurred in 14.2%,
          whereas in the older age group it occurred in
          17.5%. Chi-square test revealed this increase          groups with similar        PA readings reveals         no
          to be significant at the 5% level, but not at          significant effect of      agethis ratio (P >
                                                                                                  on
          the 1% level of confidence. Nevertheless, this          0.05). We must then conclude that the
          finding makes it greatly desirable to dis¬             relationship uncovered in the sample be¬
          tinguish more definitely between the effect of         tween PA and C/D is real and is not re¬
          PA and that of age on this ratio.                      flecting a possible age effect; on the contra¬
             In each age group, eyes were divided into           ry, the possible age effect depicted in Fig 2
          two categories depending upon the PA                   is seen to reflect the fact that higher PA is
          reading. The first included those with                 more frequent in the older age group.
          PA < 20 and the second those with PA >                    In an attempt to describe better the rela¬
          19. The frequency of the C/D ratio in each             tionship between PA and C/D ratio, the
          PA group was calculated and appears in                 sample    was   divided into different
          Fig 3 and 4. In the younger age group (Fig             groups   and the frequency of C/D ratio was
          3), the frequency of C/D > 0.3 was 13.4%               investigated in each. The results appear in
          in eyes with PA < 20 and 25.5% in those                Fig 5 and Table 1. They demonstrate clear¬
          with PA > 19. The chi-square test shows the            ly that the frequency of C/D > 0.3 in the
          increase to be statistically highly significant        normal eye increases with PA reading. The
          at the 1% level of confidence. Similarly in            chi-square test shows this increase to be
          the older age group (Fig 4), the frequency             statistically highly significant at the 1%
          of C/D ratio > 0.3 was 16.5% in eyes with              level of confidence.
          PA < 20 mm Hg and 23.2% in those with                     C-value, PJC Ratio, and the C/D Ratio.—
          PA > 19 mm Hg. The chi-square test                     In order to evaluate the relationship between
          showed this increase to be highly significant          C-value of tonography and the C/D ratio,
          at the 1% level of confidence. Thus, in each           eyes were divided into four groups depending
          age group the frequency of C/D ratio > 0.3             upon the C-value. The following ranges of
          is greater with higher pressure, indicating            C-value were used: 0.00-0.14; 0.15-0.24; 0.25-
          that the association cannot be explained by            0.34; and > 0.34. In each group the distri¬
          a possible age effect. In fact, comparing the          bution of the C/D ratio was investigated and
          frequency of C/D > 0.3 in different age                the percentage frequency of C/D ratios >


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0.3 was calculated. These appear in Fig 6                                              they share
                                                          and C-value. This indicated that
  and Table 1. It is obvious that the frequency           common   genetic determinants; the alíele
  of C/D > 0.3 increases significantly as the            pair which determines the magnitude of
  C-value becomes smaller. This increase is              ocular pressure response to topical dexa-
  statistically highly significant at the 1% level       methasone sodium phosphate was found to
  of confidence using the chi-square test-               be one of these common determinants, low
     The relationship between P0/C and C/D               response (PL), high response (PH). In the
  ratio was investigated in a similar manner.            case of C/D ratio, the positive correlation
  Eyes were divided into three groups de¬                with PA and the negative correlation with
  pending upon the P0/C ratio. The range in              C-value may also imply the sharing of com¬
  the different groups was 0-99, 100-150, and            mon genetic determinants. It is clear from
   >150. In each the frequency distribution of           the results that this is not an all or none as¬
  C/D ratio and the percentage frequency of              sociation where large C/D values are always
  C/D > 0.3 were calculated and appear in                associated with high PA and low C-values.
  Fig 7 and Table 1. Here again the frequen¬             Instead, it is a question of relative frequency
  cy of C/D > 0.3 increases progressively as             of limit values of these measures in groups
  the P0/C ratio increases. This increase is             with different C/D ratios. It is a relation¬
  statistically highly significant at the 1%             ship resulting from the interaction of more
  level of confidence using the chi-square test.         than one factor and as such offers interesting
     C/D Ratio and Values of PA, C, and                  possibilities in terms of classifying the nor¬
  Age-Corrected Standard Score for PA (Zp).              mal eye, and in terms of future prediction of
  —It is of interest to inquire whether the fre¬         the development of glaucomatous visual func¬
  quency of limit values of PA, C, and Zpe               tion loss. Now one can classify the normal
  varies significantly with the C/D ratio.               eye in terms of PA readings and classify
  Eyes were divided into three groups de¬                further eyes with similar PA readings ac¬
  pending upon the C/D ratio: 0-0.2, 0.3-0.5,            cording to the C/D ratios; similarly with the
  and 0.6-0.8. The percentage frequency of               C-values and the P0/C ratio. There is a clin¬
  PA readings > 19 mm Hg was calculated in               ical impression that in eyes with normal
  each group. Similarly, the percentage fre¬             visual fields the development of future glau¬
  quency of C-values < 0.15 and Zp > 2.00.               comatous visual field loss is related to the
  The results appear in Table 2. They indi¬              presence of a certain combination of PA, C-
  cate clearly that the frequency of these limits        value, P0/C, and C/D ratio. This intriguing
  becomes greater as the C/D ratio increases.            possibility will be elucidated in long-term
  The chi-square test shows the difference be¬           studies of normal eyes. Along the same line
  tween the third group and either one of the            of speculation the acquired enlargement of
  first two to be highly significant at the 1%           the optic cup at varying levels of PA may be
  level of confidence. Comparing the second              dependent upon the initial C/D ratio as well
  group with the first, we find the increase in          as upon the level and magnitude of change in

  frequency of limit values not significant at           PA or C-value with time. Furthermore, the
  the 1% level, but significant at the 5% level.         finding that the percentage frequency of
  It is apparent that the increase in frequency          Zp ^ 2.00 increases significantly as the C/D
  in limit values is not linear in the three             ratio increases indicates clearly that the
   groups of C/D ratio. It is markedly greater           association between C/D and PA is inde¬
  in the group with C/D ratio of 0.6 to 0.8.             pendent of age.
  This may mean that a different type of asso¬              Finally, one cannot escape the temptation
  ciation exists between these limit values and          to distinguish two types of association be¬
  the higher C/D ratios.                                 tween C/D and PA: the first, in which
                                                         common genetic factors are shared in this
             Comments and Discussion                     determination, in which case the relation¬
                                                         ship may be less dependent on time; the
     In the normal eye, the C/D ratio, PA,               second, in which this relationship is ac¬
   and C-value have been shown to be geneti¬             quired due to the influence of PA level on
   cally determined.7·8 A significant negative           the blood supply of the optic disc, thus
   correlation was found to exist between P.             producing an acquired large C/D ratio.


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This latter is more likely to be dependent              two samples a relationship between C/D
          upon time and to change with duration of                and PA that is similar to that encountered
          observation. To help distinguish between                in this study. This means that this relation¬
          these possibilities, investigations of families         ship is between C/D and PA and is not
          and of individuals tested with dexametha-               significantly modified by the presence or ab¬
          sone sodium phosphate eye drops are in                  sence of family history of glaucoma.
          progress in which the appearance of the cup               This investigation was supported in part by research
          is monitored yearly by stereophotography                grant CD-00017 from the Neurological and Sensory
          with fixed-image displacement,9 in the hope             Disease Program, Division of Chronic Diseases, and
                                                                  NB-07328 from the National Institute of Neurological
          that their comparison will elucidate some of            Diseases and Blindness.
          these intriguing speculations.
             In a preceding study,1 the distribution of             Key Words.—Cup/disc ratio; optic          cup; op¬
          the average C/D ratio of the two eyes did                      tonography; tonometry.
                                                                  tic disc;
          not differ in a sample of first-degree rela¬
          tives of patients with glaucoma and that of                  Generic and Trade Names of Drug
          the general population. Reexamination of                Dexamethasone—Decadron Phosphate, Respi-
          the data in different PA groups in the man¬               haler Decadron Phosphate, Hexadrol Phos¬
          ner described above revealed in each of the               phate, Turbinaire Decadron Phosphate.

                                                          References
             1. Armaly, M.F.: Genetic Determination of Cup/       Therapy of the Glaucomas, ed 2, St. Louis: The C.
          Disc Ratio of the Optic Nerve, Arch Ophthal             V. Mosby Co., Medical Publishers, 1965, p 108.
          78:35-43 (July) 1967.                                     6. Armaly, M.F.: Age and Sex Correction of
             2. Armaly, M.F.: The Correlation Between Ap-         Applanation Pressure, Arch Ophthal 78:480-484 (Oct)
          pearance of the Optic Cup and Visual Function,          1967.
          Trans Amer Acad Ophthal Otolaryng, to be pub-
                                                                    7. Armaly, M.F.: The Genetic Determination of
          lished.
                                                                  Ocular Pressure in the Normal Eye, Arch Ophthal
             3. Armaly, M.F.: On the Distribution of Applana-
                                                                  78:187-192 (Aug) 1967.
          tion Pressure: I. Statistical Features and the Effect
          of Age, Sex, and Family History of Glaucoma, Arch         8. Armaly, M.F.; Monstavicius, B.F.; and Sayegh,
          Ophthal 73:11-18 (Jan) 1965.                            R.E.: Ocular Pressure and Aqueous Outflow Facility
             4. Armaly, M.F.: The Des Moines Population           in Siblings, Arch Ophthal 80:354-360 (Sept) 1968.
          Study of Glaucoma, Invest Ophthal 1:618-628 (Oct)         9. Allen, L., et al: Instant Positive Photographs
          1962.                                                   and Stereograms of Ocular Fundus Fluorescence,
             5. Becker, B., and Shaffer, R.N.: Diagnosis and      Arch Ophthal 75:192-198 (Feb) 1966.




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Archopht 82 2_008

  • 1. The Cup/Disc Ratio The Findings of Tonometry and Tonography in the Normal Eye Mansour F. Armaly, MD, and Roger E. Sayegh, MD, Iowa City ied directly and significantly as that of their parents; similar relationship was seen among siblings. There was no significant age effect on this ratio. Gross inspection of the data failed to show significant relation¬ ship between appianation pressure ( ) level and the magnitude of this ratio. In another report2 it was suggested that enlargement of the optic cup may be the In eyes with normal fields, the cup/disc (C/D) first ocular evidence of the damaging effect ratio was found to be significantly related to ap- of increased ocular pressure. The question planation pressure PA level, ratio of pressure read- arose as to whether in the normal eye varia¬ ing at the beginning of the tonogram and the tion in the cup/disc (C/D) ratio is related tonographic estimate of aqueous outflow activity to variation in ocular pressure level. This (Po/C), and C-value. The frequency of C/D > 0.3 increased significantly with the PA level and with is especially interesting since each of the the magnitude of the Po/C ratio. It increased also two parameters was shown to be genetically as the C-value became smaller. This relationship determined and to be in all likelihood con¬ was independent of age or family history of trolled by multifactorial inheritance. Of glaucoma. equal interest is the possible relationship between the C/D ratio and the tonographic estimate of aqueous outflow activity (C) 1 HE RATIO between the diameter of the and the pressure reading at the beginning of optic cup and that of the optic disc in the the tonogram (P0)/C in the normal eye. normal eye of first degree relatives demon¬ An appropriate sample was studied to strated relationships indicative of its genetic evaluate the above questions. Its results un¬ determination.1 The ratio in offspring var- covered a statistically significant relation¬ Submitted for publication April 6, 1969. ship between the C/D ratio on the one hand From the Department of Ophthalmology, University and ocular pressure, C-value, and P0/C Hospitals, Iowa City. ratio on the other. In normal eyes the fre¬ Reprint requests to the Department of Ophthalmol- ogy, University Hospitals, Iowa City 52240 (Dr. quency of C/D ratio > 0.3 varied signifi¬ Armaly). cantly with variation in the above mea- Downloaded From: http://archopht.jamanetwork.com/ by a Johns Hopkins University User on 06/27/2012
  • 2. Fig 1.—Effect of PA reading on distribution of C/D Fig 2.—Effect of age on C/D ratio, with two age ratio, with two groups of readings: PA < 20 mm Hg group readings: < 40 years (light striation) and > 39 (light stippling) and PA == 20 mm Hg (dark stippling). years (dark striation). sures. It increased markedly as the increased, as the P„/C ratio became greater, Fig 3.—Effect of PA on C/D in younger age groups, and as the C-value became smaller. with two groups of PA readings: < 20 mm Hg (light stippling) and PA < 20 mm Hg (dark stippling). The Sample The sample was limited to 1,444 subjects in whom ophthalmoscopic examination of the C/D ratio was performed by a single examiner (R.S.). They fulfilled the follow¬ ing requirements: 1. Absence of ocular complaint and of history or evidence of past ocular dis¬ ease, injury, or surgery. 2. Visual acuity of 20/25 or better in each eye. 3. Distance refraction not exceeding 3 diopters of myopia or 1.5 D of astigma¬ tism. 4. Normal visual field examination of each eye using the Goldmann perim¬ was performed without dilating the pupil, eter with the I-2-e. except on rare occasions when it was felt 5. Reliable and satisfactory performance that estimation of the ratio could not be on Goldmann perimetry, applanation reliably made in the undilated pupil. This ratio was recorded separately for tonometry, and tonography. each eye. Procedure 4. Applanation tonometry and tonography were then performed by an independent The sequence of testing was as follows: research technician who was completely 1. Determination of best corrected visual unaware of the estimated C/D ratio. acuity for distance using Snellen-type In all cases the C/D ratio was recorded prior chart. to and without any knowledge of the result of 2. Goldmann perimetry using the I-2-e stim¬ tonometry and tonography. All tests were com¬ ulus. pleted on the same day. 3. Ophthalmoscopy to rule out gross abnor¬ mality to the posterior pole and to esti¬ Results mate the ratio of the horizontal diameter of the optic cup to that of the optic disc The distribution of the C/D ratio in the and record it to the nearest tenth. This normal eye was shown to differ significantly Downloaded From: http://archopht.jamanetwork.com/ by a Johns Hopkins University User on 06/27/2012
  • 3. Fig 5.—Effect of P, on C/D ratio, with percentage frequency of C/D = 0.00-0.3, inclusive, in light stip¬ pling and that of C/D > 0.3 in dark stippling. Fig 4.—Effect of PA on C/D in older age group, with two groups of PA readings: PA < 20 mm Hg (light stippling) and PA > 20 mm Hg (dark stippling). Fig 6.—Effect of C-value on C/D ratio, with per¬ Fig 7.—Effect of P„/C on C/D ratio, with percentage centage frequency of C/D = 0.00-0.3 in light stippling frequency of C/D = 0.00-0.03 in light stippling and and that of C/D > 0.3 in dark stippling. that of C/D > 0.3 in dark stippling. from the gaussian statistical distribution.1 C/D values occurred more frequently in The same was true for the distributions of eyes with > 19 than in those with PA, C, and ,,/C.3"5 Therefore, in the analy¬ PA < 20. An appropriate boundary for this ses that follow, the chi-square test will be used trend seems to be at C/D ratio of 0.3. To to evaluate the statistical significance of a evaluate this trend statistically, C/D ratios difference in frequency of certain observa¬ were divided into two subgroups: One in¬ tions. cluded C/D values of 0 to 0.3 inclusive, and Applanation Pressure and C/D Ratio.— the other included C/D values > 0.3. The The sample was divided into two groups percentage of eyes falling into each sub¬ depending upon the PA readings: the first group of C/D values was calculated in each included eyes with a PA < 20 mm Hg and PA group. In eyes with lower PA readings consisted of 2,467 eyes, and the second in¬ (PA < 20 mm Hg) 15.5% had a C/D ratio cluded those with > 19 mm Hg and > 0.3; whereas in eyes with higher PA read¬ consisted of 421 eyes. The frequency distri¬ ings (PA > 20 mm Hg) 23.3% had a C/D bution of the C/D ratio in each group ap¬ ratio > 0.3. This increase in frequency is pears in Fig 1. The frequency was expressed statistically highly significant at the 1% in percentage instead of absolute number to level of confidence using the chi-square test. permit visual comparison of the two groups. In the group with high PA readings, one It is obvious that small C/D values oc¬ expects to find older individuals to predomi¬ curred less frequently in eyes with PA > 19 nate because of the increase in PA with age than in those with PA < 20; similarly large in the normal eye.3 One might argue that if Downloaded From: http://archopht.jamanetwork.com/ by a Johns Hopkins University User on 06/27/2012
  • 4. age alone had a similar association with Table 1.—Percentage Frequency of CID > 0.3 ¡ Different PA, C, and P0/C Values large C/D ratios then the results of the preceding analysis may reflect that effect Total Frequency of C/D > rather than an effect of PA level. In a No. 0.3 in % preceding study no age effect could be un¬ Pa in mm Hg covered on the C/D ratio. The distribution <16 1,432 12.8 16-19 1,036 19.4 of C/D ratios in children did not differ 20-23 307 23.3 from that of their adult parents. However, >24 115 35.7 because of the significance of this uncertain¬ C-value in µ /mm Hg/min 194 11.8 >0.30 ty it became important to rule out such 0.25-0.34 868 12.3 association between age and C/D ratio in 0.15-0.24 1,136 16.9 <0.15 686 23.2 this present sample. The sample was di¬ vided into two age groups: One included P0/C Ratio 0-99 2,216 14.5 those whose age was < 40 years and the 100-150 474 20.0 >150 194 32.1 other included those whose age was > 39 years. The first consisted of 690 eyes and the second included 2,198. The median age for Table 2.—Percentage Frequency of Limit Values of the first was 31 years and for the second it Pa, C, and Z,. in Different C/D Ratios was 59 years. The percentage frequency dis¬ Percentage Frequency tribution of C/D ratio in each age group ap¬ C/D Total .-'-. Ratio No. Pa>19 C<0.15 Zp>2.00 pears in Fig 2. There is a suggestion that in the older age group the frequency of large 0.0-0.2 1,822 13 9.7 4.17 0.3-0.5 952 15.1 11.2 5.25 C/D ratios may be greater. In the younger 0.6-0.8 114 29 37.7 17.69 age group, C/D > 0.3 occurred in 14.2%, whereas in the older age group it occurred in 17.5%. Chi-square test revealed this increase groups with similar PA readings reveals no to be significant at the 5% level, but not at significant effect of agethis ratio (P > on the 1% level of confidence. Nevertheless, this 0.05). We must then conclude that the finding makes it greatly desirable to dis¬ relationship uncovered in the sample be¬ tinguish more definitely between the effect of tween PA and C/D is real and is not re¬ PA and that of age on this ratio. flecting a possible age effect; on the contra¬ In each age group, eyes were divided into ry, the possible age effect depicted in Fig 2 two categories depending upon the PA is seen to reflect the fact that higher PA is reading. The first included those with more frequent in the older age group. PA < 20 and the second those with PA > In an attempt to describe better the rela¬ 19. The frequency of the C/D ratio in each tionship between PA and C/D ratio, the PA group was calculated and appears in sample was divided into different Fig 3 and 4. In the younger age group (Fig groups and the frequency of C/D ratio was 3), the frequency of C/D > 0.3 was 13.4% investigated in each. The results appear in in eyes with PA < 20 and 25.5% in those Fig 5 and Table 1. They demonstrate clear¬ with PA > 19. The chi-square test shows the ly that the frequency of C/D > 0.3 in the increase to be statistically highly significant normal eye increases with PA reading. The at the 1% level of confidence. Similarly in chi-square test shows this increase to be the older age group (Fig 4), the frequency statistically highly significant at the 1% of C/D ratio > 0.3 was 16.5% in eyes with level of confidence. PA < 20 mm Hg and 23.2% in those with C-value, PJC Ratio, and the C/D Ratio.— PA > 19 mm Hg. The chi-square test In order to evaluate the relationship between showed this increase to be highly significant C-value of tonography and the C/D ratio, at the 1% level of confidence. Thus, in each eyes were divided into four groups depending age group the frequency of C/D ratio > 0.3 upon the C-value. The following ranges of is greater with higher pressure, indicating C-value were used: 0.00-0.14; 0.15-0.24; 0.25- that the association cannot be explained by 0.34; and > 0.34. In each group the distri¬ a possible age effect. In fact, comparing the bution of the C/D ratio was investigated and frequency of C/D > 0.3 in different age the percentage frequency of C/D ratios > Downloaded From: http://archopht.jamanetwork.com/ by a Johns Hopkins University User on 06/27/2012
  • 5. 0.3 was calculated. These appear in Fig 6 they share and C-value. This indicated that and Table 1. It is obvious that the frequency common genetic determinants; the alíele of C/D > 0.3 increases significantly as the pair which determines the magnitude of C-value becomes smaller. This increase is ocular pressure response to topical dexa- statistically highly significant at the 1% level methasone sodium phosphate was found to of confidence using the chi-square test- be one of these common determinants, low The relationship between P0/C and C/D response (PL), high response (PH). In the ratio was investigated in a similar manner. case of C/D ratio, the positive correlation Eyes were divided into three groups de¬ with PA and the negative correlation with pending upon the P0/C ratio. The range in C-value may also imply the sharing of com¬ the different groups was 0-99, 100-150, and mon genetic determinants. It is clear from >150. In each the frequency distribution of the results that this is not an all or none as¬ C/D ratio and the percentage frequency of sociation where large C/D values are always C/D > 0.3 were calculated and appear in associated with high PA and low C-values. Fig 7 and Table 1. Here again the frequen¬ Instead, it is a question of relative frequency cy of C/D > 0.3 increases progressively as of limit values of these measures in groups the P0/C ratio increases. This increase is with different C/D ratios. It is a relation¬ statistically highly significant at the 1% ship resulting from the interaction of more level of confidence using the chi-square test. than one factor and as such offers interesting C/D Ratio and Values of PA, C, and possibilities in terms of classifying the nor¬ Age-Corrected Standard Score for PA (Zp). mal eye, and in terms of future prediction of —It is of interest to inquire whether the fre¬ the development of glaucomatous visual func¬ quency of limit values of PA, C, and Zpe tion loss. Now one can classify the normal varies significantly with the C/D ratio. eye in terms of PA readings and classify Eyes were divided into three groups de¬ further eyes with similar PA readings ac¬ pending upon the C/D ratio: 0-0.2, 0.3-0.5, cording to the C/D ratios; similarly with the and 0.6-0.8. The percentage frequency of C-values and the P0/C ratio. There is a clin¬ PA readings > 19 mm Hg was calculated in ical impression that in eyes with normal each group. Similarly, the percentage fre¬ visual fields the development of future glau¬ quency of C-values < 0.15 and Zp > 2.00. comatous visual field loss is related to the The results appear in Table 2. They indi¬ presence of a certain combination of PA, C- cate clearly that the frequency of these limits value, P0/C, and C/D ratio. This intriguing becomes greater as the C/D ratio increases. possibility will be elucidated in long-term The chi-square test shows the difference be¬ studies of normal eyes. Along the same line tween the third group and either one of the of speculation the acquired enlargement of first two to be highly significant at the 1% the optic cup at varying levels of PA may be level of confidence. Comparing the second dependent upon the initial C/D ratio as well group with the first, we find the increase in as upon the level and magnitude of change in frequency of limit values not significant at PA or C-value with time. Furthermore, the the 1% level, but significant at the 5% level. finding that the percentage frequency of It is apparent that the increase in frequency Zp ^ 2.00 increases significantly as the C/D in limit values is not linear in the three ratio increases indicates clearly that the groups of C/D ratio. It is markedly greater association between C/D and PA is inde¬ in the group with C/D ratio of 0.6 to 0.8. pendent of age. This may mean that a different type of asso¬ Finally, one cannot escape the temptation ciation exists between these limit values and to distinguish two types of association be¬ the higher C/D ratios. tween C/D and PA: the first, in which common genetic factors are shared in this Comments and Discussion determination, in which case the relation¬ ship may be less dependent on time; the In the normal eye, the C/D ratio, PA, second, in which this relationship is ac¬ and C-value have been shown to be geneti¬ quired due to the influence of PA level on cally determined.7·8 A significant negative the blood supply of the optic disc, thus correlation was found to exist between P. producing an acquired large C/D ratio. Downloaded From: http://archopht.jamanetwork.com/ by a Johns Hopkins University User on 06/27/2012
  • 6. This latter is more likely to be dependent two samples a relationship between C/D upon time and to change with duration of and PA that is similar to that encountered observation. To help distinguish between in this study. This means that this relation¬ these possibilities, investigations of families ship is between C/D and PA and is not and of individuals tested with dexametha- significantly modified by the presence or ab¬ sone sodium phosphate eye drops are in sence of family history of glaucoma. progress in which the appearance of the cup This investigation was supported in part by research is monitored yearly by stereophotography grant CD-00017 from the Neurological and Sensory with fixed-image displacement,9 in the hope Disease Program, Division of Chronic Diseases, and NB-07328 from the National Institute of Neurological that their comparison will elucidate some of Diseases and Blindness. these intriguing speculations. In a preceding study,1 the distribution of Key Words.—Cup/disc ratio; optic cup; op¬ the average C/D ratio of the two eyes did tonography; tonometry. tic disc; not differ in a sample of first-degree rela¬ tives of patients with glaucoma and that of Generic and Trade Names of Drug the general population. Reexamination of Dexamethasone—Decadron Phosphate, Respi- the data in different PA groups in the man¬ haler Decadron Phosphate, Hexadrol Phos¬ ner described above revealed in each of the phate, Turbinaire Decadron Phosphate. References 1. Armaly, M.F.: Genetic Determination of Cup/ Therapy of the Glaucomas, ed 2, St. Louis: The C. Disc Ratio of the Optic Nerve, Arch Ophthal V. Mosby Co., Medical Publishers, 1965, p 108. 78:35-43 (July) 1967. 6. Armaly, M.F.: Age and Sex Correction of 2. Armaly, M.F.: The Correlation Between Ap- Applanation Pressure, Arch Ophthal 78:480-484 (Oct) pearance of the Optic Cup and Visual Function, 1967. Trans Amer Acad Ophthal Otolaryng, to be pub- 7. Armaly, M.F.: The Genetic Determination of lished. Ocular Pressure in the Normal Eye, Arch Ophthal 3. Armaly, M.F.: On the Distribution of Applana- 78:187-192 (Aug) 1967. tion Pressure: I. Statistical Features and the Effect of Age, Sex, and Family History of Glaucoma, Arch 8. Armaly, M.F.; Monstavicius, B.F.; and Sayegh, Ophthal 73:11-18 (Jan) 1965. R.E.: Ocular Pressure and Aqueous Outflow Facility 4. Armaly, M.F.: The Des Moines Population in Siblings, Arch Ophthal 80:354-360 (Sept) 1968. Study of Glaucoma, Invest Ophthal 1:618-628 (Oct) 9. Allen, L., et al: Instant Positive Photographs 1962. and Stereograms of Ocular Fundus Fluorescence, 5. Becker, B., and Shaffer, R.N.: Diagnosis and Arch Ophthal 75:192-198 (Feb) 1966. Downloaded From: http://archopht.jamanetwork.com/ by a Johns Hopkins University User on 06/27/2012