562 AMERICAN JOURNAL OF OPHTHALMOLOGY
retinal vein occlusion were present. Obstruc-
Fig. 1 (Kimmel and associates). Periphlebitis of the
inferotemporal branch retinal vein with nerve fiber
layer hemorrhages inferiorly and temporal to the
fovea indicative of branch vein occlusion.
months after the first examination, visual acu-
ity was R.E.: 20/30 and L. E.: 20/20. The right
eye had less periphlebitis of the inferotemporal
branch retinal vein. Fluorescein angiography
demonstrated capillary nonperfusion without
neovascularization or significant macular
edema (Fig. 2).
A branch retinal vein obstruction is usually
caused by thrombosis of the vein at a site of
arteriovenous crossing, where the artery and
vein share a common adventitial sheath. Our
patient with sarcoidosis had an inferotemporal
branch retinal vein occlusion at a site of intense
periphlebitis. No other risk factors for branch
Fig. 2 (Kimmel and associates). Fifteen months
after the initial examination. Note capillary nonper-
fusion without neovascularization.
May, 1989
tion of a small peripheral retinal venule with
subsequent ischemia and neovascularization is
well documented in ocular sarcoidosis.v' Al-
though less common, larger retinal vessels may
also become inflamed and subsequently oc-
cluded as shown in this case.
References
1. Gass, J. D. M., and Olson, C. L.: Sarcoidosis
with optic nerve and retinal involvement. Arch.
OphthalmoI. 94:945, 1976.
2. Sanders, M. D., and Shilling, J. S.: Retinal, cho-
roidal, and optic disc involvement in sarcoidosis.
Trans. OphthalmoI. Soc. U.K. 96:140, 1976.
3. Duker, J. S., Brown, G. c.. and McNamara, A.:
Proliferative sarcoid retinopathy. Ophthalmology
95:1680, 1988.
4. Asdourian, G. K., Goldberg, M. F., and Busse,
B. J.: Peripheral retinal neovascularization in sar-
coidosis. Arch. OphthalmoI. 93:787, 1975.
Systemic Absorption of Ophthalmic
Cyclopentolate
Timo Kaila, M.D.,
Risto Huupponen, M.D.,
Lotta Salminen, M.D.,
and Esko Iisalo, M.D.
Derartments of Pharmacology (T.K. and R.H.), Clin-
ica Pharmacology (R.H. and E.I.), and Ophthalmol-
ogy (L.S.), University of Turku. Supported in part by
the Paulo Foundation, Helsinki.
Inquiries to Risto Huupponen, M.D., Departments of
Pharmacology and Clinical Pharmacology, Kiinamql-
lynkatu 10, SF-20520 Turku, Finland.
Cyclopentolate, a synthetic antimuscarinic
agent, produces rapid and intense mydriasis
and cycloplegia of moderate duration after ocu-
lar administration. Ophthalmic cyclopentolate
is used for testing cycloplegic refraction and for
ophthalmoscopy. Its use both in children and
adults has been associated with acute psychotic
reactions' as well as one fatality. We undertook
this study to quantitate the systemic absorption
of cyclopentolate from eyedrops.
Six subjects, four men and two women with a
mean ± S.D. age of 33 ± 9 years, volunteered
Vol. 107, No.5 Letters to the Journal 563

for this study. When recumbent, two 30-f.,d TABLE

drops of 1% cyclopentolate (pH 5) were in- CYCLOPENTOLATE PLASMA CONCENTRATIONS
stilled into the lower cul-de-sac of one eye at a (NG/Ml)*
five-minute interval using a micropipette.
Blood samples were drawn into edetic acid TIME SINCE INSTILLATION OF LAST DROP (MIN)
SUBJECT
tubes from an antecubital vein using an intra- NO. 5 10 15 30 45 60 90
venous cannula, and the plasma was immedi-
ately separated from the blood by centrifuga- 1 2.2 3.3 2.9 2.2 2.7 1.9 1.9
tion. The blood samples were taken before the 2 11.8 13.5 15.5 4.7 3.5 9.5 6.1
cyclopentolate application and five, ten, 15, 30, 3 7.7 3.5 3.6 2.1 1.8 2.4 1.2
45, 60, and 90 minutes after the last drop was 4 9.1 6.7 6.3 4.1 3.1 2.1 1.7
instilled. The subjects remained recumbent up 5 7.1 8.5 7.5 NO' 2.3 1.5 3.2
to 30 minutes after drug instillation. 6 5.3 4.5 5.9 3.3 2.9 2.3 1.5
The radioreceptor assay used was a modifica- Mean 7.2 6.7 7.0 3.3 2.7 3.3 2.6
tion of the assay described previously for the S.D. 3.3 3.9 4.5 1.1 0.6 3.1 1.9
determination of ipratropium bromide, a po-
*Cyclopentolate concentration before drug instillation was un-
tent anticholinergic in plasma." Two milliliters
detectable in all subjects.
of the edetic acid plasma sample was mixed
with 200 ul of 0.01 M natriumpicrate solution. 'NO, not determined.
The cyclopentolate was extracted into
dichloroethane, after which 1.5-ml aliquots
were evaporated to dryness under a nitrogen radioreceptor assay, appears rapidly in the
stream. The evaporated samples were equili- blood stream after instillation. This finding is in
brated with 0.5 nM of tritiated N-methyl scopol- accordance with results of studies on ophthal-
amine (74 Ci/mmol) and with a 0.3-nM musca- mic atropine and timolol, where drug plasma
rinic receptor concentration from rat brain. The concentrations peaked ten minutes after the
cyclopentolate concentrations in the unknown drug application.v'
samples were determined against a calibration The sensitivity of our radioreceptor assay for
curve obtained from plasma standards of cyclopentolate allows the determination of
cyclopentolate prepared in drug-free plasma. even very low cyclopentolate plasma levels
The sensitivity of the method, defined in terms (150 pg/ml). The radioreceptor assays, howev-
of cyclopentolate units, was 150 pg/ml. The er, are semiqualitative, since they measure
intra-assay and interassay variations for the only the enantiomer, which binds to receptors
200-pg/ml standard were within 20% and those with a high affinity. Possible metabolites and
for the 2.0-ng/ml standard within 10%. other drugs in plasma with a high affinity to the
The mydriatic effect of cyclopentolate was same receptors interfere with the results.
estimated by measuring pupil size with a pupil- The first peak of cyclopentolate in plasma is
lometer at the same time the blood samples probably the result of drug absorption from the
were taken. The lightness of the room was kept conjunctival surface. In humans, the conjuncti-
constant over the entire study period. val surface area is about 17-fold larger than the
Ocular cyclopentolate was rapidly absorbed corneal area,' which enhances systemic drug
systemically, the peak concentrations being absorption in relation to its ocular penetration.
reached in 10 ± 5 minutes (mean ± S.D.) after In some subjects a second peak occurred
instillation of the last drop. Short-lasting burn- (Table). This probably reflects drug absorption
ing sensations in the eye and tearing were from more distal sites after drainage through
frequently reported after drug instillation. the nasolacrimal duct. A second peak after
Individual variation in the amount of the instillation of timolol has also been docu-
drug absorbed into systemic circulation was mented.
notable. Peak concentrations ranged from 3.3 In preterm infants, 0.5% ocular cyclo-
to 15.5 ng/ml, with a mean of 8.3 ± 4.1 ng/ml pentolate reduces gastric acid secretion and
(Table). volume. This effect, together with the psychot-
Pupil size increased from the basal value of ic reactions occurring particularly in children,
3.8 ± 0.8 mm to a maximum of 8.3 ± 0.5 mm calls for pharmacokinetic studies after instilla-
(P< .001, t-test for paired data) at ten minutes tion of cyclopentolate at a younger age. A
and remained constant for up to 90 minutes. reduction in the systemic absorption of oph-
Ophthalmic cyclopentolate, as measured by thalmic cyclopentolate without a decrease in its
564 AMERICAN JOURNAL OF OPHTHALMOLOGY
ocular actions should increase the safety of its
use. Developing a safer drug formulation for
cyclopentolate is a challenge for pharmacists
working with ocular drugs.
ACKNOWLEDGMENT
Mrs. Ulla Heikonen provided technical
assistance in cyclopentola te analysis.
References
1. Khurana, A. K., Ahluwalia, B. K., Rajan, c..
and Vohra. A. K.: Acute psychosis associated with
topical cyclopentolate hydrochloride. Am. J. Oph-
thalmol. 105:91, 1988.
2. Ensinger, H. A., Wahl, D., and Brantt, U.:
Radioreceptor assay for determination of the
antimuscarinic drug ipratropium bromide in man.
Eur. J. Clin. Pharmacol. 33:459, 1987.
3. Lahdes, K., Kaila, T., Huupponen, R.,
Salminen, L., and Iisalo, E.: Systemic absorption of
topically applied ocular atropine. Clin. Pharmacol.
Ther. 44:310,1988.
4. Kaila, T., Salminen, L., and Huupponen, R.:
Systemic absorption of topically applied ocular
timolol. J. Ocul. Pharmacol. 1:79, 1985.
5. Watsky, M. A., Jablonski, M. M., and
Edelhauser, H. F.: Comparison of conjunctival and
corneal surface areas in rabbit and human. Curro Eye
Res. 7:483, 1988.
Mean Visual Acuity
Alejandro Aguirre Vila-Coro, M.D.,
and Antonio Aguirre Vila-Coro, M.D.
University of Texas Health Science Center at Hous-
ton, Hermann Eye Center.
Inquiries to Alejandro Aguirre Vila-Cora, M. D., Dracena
40,28016 Madrid, Spain.
Papers reporting the visual acuities of a series
of patients often erroneously calculate the
mean visual acuities. A common error lies in
calculating the mean values of the denomina-
tors instead of the mean values of the whole
fractions. Converting the visual acuities into
decimals and then determining their mean
value avoids this error. For example, in two
patients whose visual acuities are 20120 and
20/400, to calculate the mean visual acuity cor-
rectly, the fractions are first converted into
decimals, so that 20/20 becomes 1.00 and 20/400
becomes 0.05.
May, 1989
The mean of the converted visual acuities,
(1.00 + 0.05)/2, equals 0.525. If desired, the
mean thus obtained in decimals can be convert-
ed back into a Snellen fraction. The numerator
of the Snellen fraction remains 20, and the
value of the denominator is obtained by divid-
ing 20 by the mean; in this case 20/0.525 =
38.09. The denominator can then be rounded to
the nearest Snellen measurement, so that 38.09
becomes 40.
We recommend that mean visual acuities, if
reported, be obtained by first converting the
fractions to decimals.
Correspondence
Correspondence concerning recent articles or other mate-
rial published in THE JOURNAL should be submitted within
six weeks of publication. Correspondence must be typed
double-spaced, on 8Y2 x l l-inch bond paper with 1 1/2-inch
margins on all four sides and should be no more than two
typewritten pages in length.
Every effort will be made to resolve controversies between
the correspondents and the authors of the article before
publication.
Visual Results With Low-Vision Aids in
Age-Related Macular Degeneration
EDITOR:
In the article "Visual results with low-vision
aids in age-related macular degeneration" by
F. P. Nasrallah, A. E. Jalkh, G. R. Friedman,
C. L. Trempe, J. W. McMeel, and C. L.
Schepens (Am. J. Ophthalmol. 106:730, De-
cember 1988), we commend the authors for
their interest in low vision and for their effort
in conducting this retrospective study. We
would like to make the following comments.
The data included with the paper are pre-
sented in a way that seems to support the
commonly held notion that "near vision" or
"reading vision" can vary widely for the
same level of distance vision. We maintain
that this seeming discrepancy is largely the
result of inaccuracies in clinical measurement.
We would like to present Nasrallah and asso-
ciates' data in a way that shows they actually
are consistent with this notion.
It is now generally accepted that steps of