Adult Inclusion Conjunctivitis
Clinical Characteristics and Corneal
Susan Stenson, MD
Twenty-five consecutive cases of ad-
\s=b\
ult inclusion conjunctivitis were studied.
Diagnosis was based on the finding of
typical Halberstaedter-Prowazek inclu-
sion bodies on conjunctival scrapings.
Corneal involvement was common (20/25
patients); most frequent was superficial
epithelial keratitis (15/25). Other changes
seen included subepithelial nummular
keratitis (6/25), marginal keratitis (2/25),
and superior limbal swelling and pannus
(4/25). There seemed to be a predilection
for involvement of the upper half of the
cornea. Conjunctival scarring occurred in
one patient only. Associated genitouri-
nary symptoms were spontaneously re-
ported in three patients only; however, on
careful questioning, an additional 12
patients were found to have a history of
urethritis or cervicitis. A comparison with
viral follicular conjunctivitis is made. The
location and pattern of keratopathy, asso-
ciated genitourinary complaints, mucopu-
rulent nature of discharge, and lack of
response to standard topical therapy
would seem to suggest chlamydial cause.
Conjunctival scrapings are very helpful in
differential diagnosis between viral and
chlamydial conjunctivitis.
(Arch Ophthalmol 1981;99:605-608)
"inclusion is seen in
conjunctivitis
adults as an acute or chronic infec¬
tion. Its clinical presentation as a fol-
licular conjunctivitis can be indistin¬
guishable from viral processes. Reli¬
able differentiation is possible only
through culture, serologie, and cyto-
Accepted for publication July 5, 1980.
From the Department of Ophthalmology, New
York University Medical Center, New York.
Reprint requests to 333 E 34th St, Suite 1E,
New York, NY 10016 (Dr Stenson).
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Changes
logic studies.
The aim of this study was to evalu¬
ate the clinical characteristics, espe¬
cially the corneal changes, observed in
adult follicular conjunctivitis due to
Chlamydia so as to aid in its identifi¬
cation and differentiation from simi¬
lar cases of adenoviral infection.
SUBJECTS AND METHODS
Twenty-five consecutive cases of inclu¬
sion conjunctivitis were analyzed. All adult
patients with acute or chronic follicular
conjunctivitis were studied. Conjunctival
cultures for bacteria and fungi were rou¬
tinely obtained. Viral cultures for herpes
and adenovirus were done in selected cases
seen during the first several days of dis¬
ease. Scrapings of the upper and lower
palpebrai conjunctiva were taken and
stained with Giemsa for microscopic exam¬
ination.
Cytologie findings were used for the
differential diagnosis of viral and inclusion
follicular conjunctivitis. In viral processes,
the inflammatory cell response is predomi¬
nantly mononuclear, with many lympho¬
cytes and monocytes. In inclusion conjunc¬
tivitis, the cell response is intense and
polymorphic with many neutrophils, lym¬
phocytes, and monocytes; neutrophils are
usually most numerous. Plasma cells are
also frequently found. The pathognomonic
cytologie finding, however, is the baso-
philic cytoplasmic inclusion body of Hal-
berstaedter-Prowazek, typically seen "cap¬
ping" the nucleus of epithelial cells (Fig 1
and 2).
In this series, the diagnosis of inclusion
conjunctivitis was based on cytologie find¬
ing of chlamydial inclusions in Giemsa-
stained conjunctival scrapings. The other
methods of identifying this organism-
direct culture using yolk sacs or irradiated
McCoy cell cultures and serologie studies
(complement fixation or microimmuno-
fluorescence)—were not routinely done.
RESULTS
A total of 25 cases of adult inclusion
conjunctivitis were diagnosed based
on typical cytologie findings. Of these,
18 were seven were chronic
acute and
(acute wasconsidered less than one
month's duration). Infection varied
from four days to two years in dura¬
tion. Ages ranged from 14 to 45 years,
with an average of 26 years. There
were 16 males and nine females.
Infection was bilateral in 16 cases; in
the other nine, the left eye was slight¬
ly more frequently affected (five of
nine patients). There was a history of
a concomitant conjunctivitis in the
sexual partner in four cases. Overall,
systemic symptoms were uncommon.
Only three patients reported an
accompanying urethritis or cervicitis;
however, in an additional 12 subjects,
some genitourinary complaints could
be elicited on careful questioning.
Regional adenopathy was usually
present (moderate in 13), but not a
prominent feature.
The conjunctivitis was uniformly
follicular in type with involvement of
both upper and lower fornices; in sev¬
eral cases, the upper tarsal involve¬
ment was predominant. Conjunctival
chemosis and edema of the plica and
semilunar fold were often present in
acute infections, but to a lesser extent
than with viral conjunctivitis. Hemor¬
rhages were not observed in this se¬
ries. Membranes were seen in four
patients with florid conjunctival reac¬
tion; these occurred on both upper and
lower lids. No accompanying iritis was
found.
Overall, corneal changes were ob¬
served in 20 patients. Although the
 Fig 1.—Mononuclear response in viral conjunctivitis (left) compared
inflammatory cell response in inclusion conjunctivitis (right) with
(arrow) (Giemsa, x 200).
Fig 2.—Halberstaedter-Prowazek inclusion
(Giemsa, 500).
pattern of involvement varied, there
was a for in¬
striking predilection
volvement of the upper half of the
cornea. Epithelial keratitis was the
most common finding (15/25 pa¬
tients). This was usually in the form of
either multiple small-staining superfi¬
cial punctate lesions or minute flat
epithelial dots. Subepithelial nummu-
lar lesions, reminiscent of the keratop¬
athy of epidemic keratoconjunctivitis,
were also frequent (6/25); here again,
involvement was typically in the upper
one third of the cornea. More unusual
changes included marginal keratitis in
two patients, a phlyctenular lesion in
another, and a peculiar epaulette-like
pannus at the upper limbus in two more
(Fig 3 through 10).
Many of the patients had been pre-
treated with a variety of topical anti¬
biotic-steroid combinations without
improvement. None reported any re¬
cent travel outside the greater New
York area. After the diagnosis was
established, each patient received a
combination of topical erythromycin
ointment and oral tetracycline hy-
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with polymorphic
inclusion bodies
Fig 3.—Acute inclusion conjunctivitis in
21-year-old man with nonspecific urethri-
tis: follicles lower fornix.
Fig 4.—Follicles of upper fornix and tarsus
in same patient as Fig 3.
body (arrow) in conjunctival epithelial cell
drochloride (1
g/day) for three weeks.
Asymptomatic sexual partners also
received three-week courses of oral
tetracycline. Complete resolution oc¬
curred in all but one patient, a 21-
year-old man with a two-year history
of follicular conjunctivitis. In this
case, symptoms abated with treat¬ Fig 5.—Inclusion conjunctivitis with sub¬
ment and follicles gradually re¬ epithelial keratitis involving upper cornea
in 32-year-old woman with two-month his¬
gressed, but not completely. In anoth¬
er chronic case—a 26-year-old woman
tory of refractory follicular conjunctivitis.
with a six-month history of severe
membranous follicular conjunctivitis
with epithelial keratitis—infection
cleared with treatment, but scarring
of the palpebrai conjunctiva, especial¬
ly the upper part, resulted. (This was
the only case in this series where
conjunctival cicatrix was seen.) About
16 months later, she had a recurrence
of symptoms, having recently reinsti-
tuted sexual relations with her former
untreated partner. Cytologie findings
again demonstrated an intense poly¬
morphic inflammatory cell response Fig 6.—Sixteen-year-old boy with three-
with inclusion bodies. Repeated treat¬ week history of follicular conjunctivitis due
ment with oral tetracycline resolved to Chlamydia: marginal keratitis involving
the infection. upper cornea.

Fig 7.—Inclusion conjunctivitis with focal
superior pannus in 25-year-old woman
with bilateral involvement for one month.
Fig 8.—Inclusion conjunctivitis with su¬
perior limbal swelling in 29-year-old man
with one-week history of red eye.
Fig 9.—Inclusion conjunctivitis with su¬
perior "epaulette" pannus in 22-year-old
man with six-week history of follicular con¬
junctivitis OS.
Fig 10—Superior "epaulette" pannus and
subepithelial keratitis in 40-year-old man
with bilateral follicular conjunctivitis for
three weeks with no response to topical
steroid therapy.
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Comparison of Viral and
Incubation
Unilateral, bilateral
Ages
Systemic findings
Discharge
Course
Adenopathy
Follicles
Scarring
Keratitis
Cytologie findings
Response to tetracycline
Response to steroid
COMMENT
Inclusion conjunctivitis can be
as an acute or chronic follicular
junctivitis, usually occurring in adults
during their sexually active years or
in neonates from infected mothers.
The differential diagnosis of adult
inclusion conjunctivitis and viral folli¬
cular conjunctivitis can be difficult. In
follicular conjunctivitis due to viruses
other than the common adenovirus,
accompanying cutaneous and corneal
changes are usually diagnostic. In
herpes zoster, associated skin lesions
distributed along the ophthalmic
branches of the trigeminal nerve are
pathognomonic. With acute herpes
simplex, the presence of skin vesicles,
hypesthesia, and corneal (and rarely
conjunctival) dendrites is diagnostic.
The waxy umbilicated nodules of mol-
loscum contagiosum occurring along
the lid margins and associated with a
follicular conjunctivitis are character¬
istic. Conjunctivitis is frequently seen
in infections with RNA viruses. Here,
accompanying systemic signs (eg, the
skin rash of measles or the salivary
and lacrimal gland involvement with
mumps) should suggest the cause. In
adult inclusion conjunctivitis, the dif¬
ferential diagnosis is usually between
adenoviral and chlamydial infection.
Certain clinical characteristics can be
useful1 (Table). Incubation time is
longer with Chlamydia. Although res¬
piratory symptoms can rarely be seen
with inclusion conjunctivitis, genito¬
urinary problems are more frequent;
however, as can be seen in this series,
these are often not noticeable and
careful questioning may be necessary
to elicit signs of a nonspecific urethri-
tis or cervicitis. This is contrasted to
viral conjunctivitis, where accom¬
panying respiratory tract infection is
Chlamydial Follicular Conjunctivitis
Inclusion Viral
4-19 Days 3-7Days
Usually bilateral Usually unilateral
Young adults; neonates All ages
Genitourinary Respiratory
Mucopurulent Watery
Chronic Self-limited
Rare
Rare
Common; epithelial and Common; early epithe¬
subepithelial; fre¬ lial; late subepithe¬
quent limbal involve¬ lial; diffuse involve¬
ment; upper half of ment
the cornea
Inclusion bodies; poly¬ Mononuclear response
morphic
quite common. Except in viral follicu¬
seen lar conjunctivitis due to herpes sim¬
con¬ plex type 2, genital involvement does
not occur. Discharge is usually more
copious and mucopurulent with inclu¬
sion conjunctivitis, compared with the
scanty watery drainage with viral
processes. Regional lymphadenopathy
is observed in both types of follicular
conjunctivitis; however, involvement
seems to be more marked with
viruses. No subconjunctival hemor¬
rhages were found in any of the cases
reported herein; although not com¬
mon, petechial changes are recognized
to occur in viral conjunctivitis. Mem¬
branes are uncommon and seem to be
nonspecific, being found in both, prob¬
ably more as a manifestation of the
severity of the infection than the
cause. Chemosis and edema of the
plica and semilunar fold are also com¬
mon findings; these are generally
somewhat more prominent in viral
conjunctivitis. Age grouping in the
sexually active years and lack of
improvement after two weeks of con¬
servative treatment should also raise
strong suspicion of a chlamydial
cause. Lack of response to or even
exacerbation of symptoms with topi¬
cal steroids further suggests inclusion
conjunctivitis.2
The question of corneal changes in
inclusion conjunctivitis raises the
issue of its differentiation from tra¬
choma. Long recognized as a major
cause of blindness worldwide, tracho¬
ma affects the eyes primarily, being
characterized by stages of recurrent
activity and cicatrization, eventually
leading to corneal scarring and visual
loss. Systemic involvement is only sec¬
ondary; genital recovery of the orga¬
nism, although infrequent, has been
reported.' In contrast to this, the ocu-
 larchanges of inclusion conjunctivitis
are less common and secondary in
importance to genitourinary involve¬
ment. Without proper treatment, in¬
fection either pursues a benign self-
limited course or leads to chronic
symptoms. Scarring and visual loss
are virtually unheard of with inclusion
conjunctivitis. As opposed to the geo¬
graphic distribution and age predilec¬
tion for the very young and old with
trachoma, inclusion conjunctivitis oc¬
curs sporadically and affects primari¬
ly either neonates or young adults. It
should be noted, however, that al¬
though the clinical pictures differ and
certain serotypes of C trachomatis are
considered pathognomonic for tracho¬
ma (A, Ba, and C) and inclusion con¬
junctivitis (D to K), overlap does exist.
There is at least one report of a volun¬
teer inoculated with a chlamydial
strain from a neonate with inclusion
blennorrhea who developed ocular
changes indistinguishable from tra¬
choma.'
Several types of superficial corneal
involvement in adult inclusion con¬
junctivitis have been described. Daw-
son and Schachter reported corneal
findings in 17 cases and found pannus
in three, epithelial keratitis in 16,
marginal infiltrates in 12, and
epidemic keratoconjunctivitis-like
changes in two.5 Other authors have
denied the occurrence of any notewor¬
thy corneal changes in pure inclusion
conjunctivitis. Jones et al6 postulated
a third type of trachoma-inclusion
conjunctivitis (TRIC) ocular involve¬
ment: TRIC agent punctate keratitis,
or TPK. Patients with this condition,
considered clinically intermediate be¬
tween trachoma and inclusion con¬
junctivitis, are usually in their 20s,
frequently have elicitable genitouri¬
nary symptoms and typical inclusion
bodies in conjunctival scrapings. Cor¬
neal involvement is primarily in the
form of punctate stromal keratitis.
Serotype distinctions for TPK have
1. Schacter J, Dawson CR: Human Chlamydial
Infections. Littleton, Mass, PSG Publishing Co
Inc, 1978, pp 97-110.
2. Ormsby HL, Thompson GA, Cousineau GG,
et al:Topical therapy in inclusion conjunctivitis.
Am J Ophthalmol 1952;35:1811-1814.
3. Jones BR: Ocular syndromes of TRIC virus
infection and their possible genital significance.
Br J Vener Dis 1964;40:3-18.
4. Jones BR, Al-Hussaini MK, Dunlop EMC:
Infection of the eye and genital tract by TRIC
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not been done.
Several studies have recorded clini¬
cal characteristics of experimentally
induced inclusion conjunctivitis. Tar¬
izzo et al7 inoculated 13 blind volun¬
teers with the Kami strain
(TRIC/
/JAP/TOKU-3/ON). Conjunctival re¬
action was primarily in the lower lid.
A perikeratic infiltrate developed in
eight of 12 cases; no other corneal
changes were observed except for
upper limbal follicles in one case.7
This is in contrast to a second study
of experimental inclusion conjunctivi¬
tis in volunteers inoculated with
(TRIC/ /USA-Cal-9-ON) and (TRIC/
/USA-Cal/Cal-15-ON). Follicles oc¬
curred in the lower fornices and upper
tarsal plate. Conjunctival inflamma¬
tion peaked two weeks after exposure.
No conjunctival scarring was found
despite repeated exposure to the
agent for up to two years. Keratitis
was a regular feature of the disease.
Epithelial keratitis was most fre¬
quent; other involvement took the
form of marginal infiltrates, large
central subepithelial lesions, limbal
swelling, and micropannus (especially
in reinfections). In 44 primary infec¬
tions, epithelial keratitis occurred in
42 patients, marginal infiltrates in 40,
small central infiltrates in 33, and
large in 18. The frequency of keratitis
overall did not increase with reinfec¬
tion.8
The nature and frequency of cor¬
neal changes found in the series of
patients reported herein correlates
well with prior experimental and clin¬
ical reviews. Significant corneal
changes occurred in 20/25 cases. Most
frequent was superficial epithelial
keratitis, indistinguishable from that
seen in other conditions except for its
preferential involvement of the upper
cornea. Subepithelial keratitis rang¬
ing from fine extensions of more
superficial involvement to nummular
changes mimicking the keratitis of
epidemic keratoconjunctivitis was
References
agent: III. Ocular syndromes associated with
infection of the genital tract by TRIC agent. Rev
Int Trach Pathol Ocul Trop Subtrop 1965;42:27\x=req-\
43.
5. Dawson CR, Schachter J: TRIC agent infec-
tions of the eye and genital tract. Am J Ophthal-
mol 1967;63:1288-1297.
6. Jones BR, Al-Hussaini MK, Dunlop EM, et
al: Infection by TRIC agent and other members
of the Bedsonia group, with a note on Reiter's
disease: I. Ocular disease in the adult. Trans
also common; here, too, the superior
cornea was affected.
predominantly
More unusual changes included margi¬
nal infiltrates, phlyctenular changes,
and superior limbal swelling and scar¬
ring. Corneal changes overall seemed
more frequent with longer duration
and increased severity of disease;
however, the patient with the longest
history of involvement (two years)
exhibited no corneal pathologic find¬
ings, whereas the superior limbal
swelling in another occurred after
only one week of infection. In the one
case with recurrence, mild conjuncti¬
val scarring developed, but no corneal
involvement other than mild transient
punctate keratitis was noted.
Overall, the predilection for upper
corneal involvement, several atypical
forms of keratopathy, and the fre¬
quent occurrence of keratitis early in
the course of the infection, offer some
clinical characteristics helpful in dis¬
tinguishing chlamydial involvement
from cases of viral conjunctivitis
where the corneal changes involve the
entire surface (with perhaps some
preference for central and inferior
sites) and changes typically take the
form of either an early diffuse epithe¬
lial keratitis or a late subepithelial
nummular keratitis.
Keratitis in adult inclusion conjunc¬
tivitis seems to be more common in
occurrence and more variable in form
than generally believed. The location
and pattern of keratopathy—
combined with other clinical charac¬
teristics, including genitourinary in¬
volvement, lack of response to topical
steroids, and quality of discharge-
would seem to be helpful in the clinical
differentiation of chlamydial and
viral follicular conjunctivitis.
This research was supported in part by a
departmental grant from Research to Prevent
Blindness.
Walter Lentschner and Robert Newman pro¬
vided photographic assistance.
Ophthalmol Soc UK 1966;86:291-308.
7. Tarizzo ML, Nataf R, Nabli B: Experimental
inoculation of 13 volunteers with agent isolated
from inclusion conjunctivitis. Am J Ophthalmol
1967;63:1120-1128.
8. Dawson CR, Wood TR, Rose L, et al: Exper-
imental inclusion conjunctivitis in man: III. Ker-
atitis and other complications. Arch Ophthalmol
1967;78:341-349.