British Journal of Ophthalmology 1996;80:895-899

Ciliary body enlargement and cyst formation inuveitis

Ronald C Gentile, JeffreyM Liebmann, Celso Tello, Zeev Stegman, Scott S Weissman,Robert Ritch

Ocular ImnagingCenter, The New YorkEye and Ear Infirmary,New York, and theDepartments ofOphthalmology, TheNew York Eye and EarInfirmary, New York,and New York MedicalCollege, Valhalla, NY,USAR C GentileJM LiebmannC TelloZ StegmanS S WeissmanR Ritch

Correspondence to:Robert Ritch, MD,Glaucoma Service, The NewYork Eye and Ear Infirmary,310 East 14th Street, NewYork, NY 10003, USA.

Accepted for publication28 June 1996

AbstractBackground-Acute anterior uveitis hasdiverse causes and systemic associations.Inflammation is predominantly localisedto the iris and pars plicata. little is knownabout the in vivo effects of uveitis on

ciliary body anatomy.Methods-Bilateral, high frequency, highresolution, ultrasound biomicroscopy wasperformed on consecutive patients withunilateral anterior uveitis to evaluate cili-ary body anatomy. Imaging was repeatedwhen possible during the clinical course.The cross sectional area of the anteriorciliary body was measured using imageprocessing and analysis software. Meas-urements from the uveitic eyes were com-pared with the fellow eyes and the effect oftreatment was evaluated.Results-Fourteen patients were enrolled.Ultrasound biomicroscopy demonstrateda larger ciliary body cross sectional area

in the uveitic eyes compared with thefellow, clinically uninvolved eyes (2.45 (SD0.48) mm' versus 1.55 (SD 0.15) mm2, (p =0.0000; paired t test)). A ciliochoroidaleffusion was present in one uveitic eye.Epithelial cysts were imaged bilaterally infour uveitic patients (290/6) and unilater-ally in unaffected eyes of two uveiticpatients. Ciliary body cross sectional areadecreased following steroid therapy (p =

0.0001; paired t test). New cysts were notedin three uveitic eyes during the follow upperiod and in none of the fellow, unaf-fected eyes.Conclusion-Ultrasound biomicroscopyoffers a new approach to the evaluation ofanterior uveitis. The response to treat-ment can be evaluated objectively andtherapeutic efficacy can be more easilyassessed. It has the potential to help eluci-date the pathophysiology and anatomicalchanges of this heterogeneous group ofdisorders.(BrJ Ophthalmol 1996;80:895-899)

Anterior uveitis is characterised by inflamma-tion predominantly localised to the iris andpars plicata of the ciliary body, accompaniedby a breakdown of the blood-aqueous barrierand increased aqueous protein and cells. Sinceno direct clinical pathological studies havebeen conducted in the acute phase of anterioruveitis,' and since visualisation of the ciliarybody in vivo is difficult with slit-lamp biomi-

croscopy, little is known about the effect ofacute anterior uveitis on ciliary body anatomy.Improved imaging of the ciliary body in vivo

is possible using high frequency ultrasoundbiomicroscopy (UBM).' This has proved to bevaluable in elucidating the anatomy and patho-physiology of a variety of anterior segmentdisorders.'3 After noting ciliary body enlarge-ment and epithelial cysts of the pars plicata ina patient with anterior uveitis, we performedthis prospective pilot study to detect in vivoalterations of ciliary body appearance inanterior uveitis.

Patients and methodsAfter informed consent, consecutive patientswith unilateral anterior uveitis underwent oph-thalmic examination and UBM of both eyes.Examination included visual acuity testing,slit-lamp biomicroscopy, tonometry, gonio-scopy, and indirect ophthalmoscopy. Diagnosisand classification were based on history andclinical examination using guidelines describedby Tessler.9 Patients with a history of trauma,evidence of posterior uveitis, intermediateuveitis, or postoperative inflammation wereexcluded. Anterior chamber reaction wasgraded according to the method of Hogan etal.10 Laboratory evaluation, skin testing, andchest x ray were performed when clinicallyindicated.High resolution UBM (Zeiss-Humphrey,

San Leandro, CA, USA) is based on highfrequency transducers, incorporated into a Bmode clinical scanner. The device and tech-nique of UBM have been reported in detailelsewhere.2""12 Our current device uses a 50MHz transducer, achieves a tissue resolution of50 pm., and has a tissue penetration of 4-5 mm.Scanning is performed with the patient in thesupine position using topical anaesthesia. A 20mm eye cup is placed on the eye and filled withsaline solution," which serves as a couplingmedium. The ultrasound probe is placedapproximately 2-3 mm from the ocular sur-face. Fine movement of the probe is performedmanually to visualise different locations of theanterior segment. Images are captured on avideo printer.The ciliary body was imaged for 360

degrees. Multiple transverse images of theanterior segment were taken in all fourquadrants. When a cyst was identified it waslocalised to within 1 clock hour and wasconfirmed with a sagittal cross sectional image.The diameter of the cyst was approximated tothe nearest 50 gm. All UBM scans were

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Table 1 Patient data and ophthalmic examination

History ofPatient Age Sex Uvettic eye Type Cells/flare Presumed cause uveitis

1 16 M L NG +1/+3 ID No2 55 F R G +3/+3 ID* No3 46 F R NG +2/+2 ID* No4 47 F R NG +2/+1 ID No5 29 M L G +3/+3 ID*t No6 29 M L NG +3/+4 ID*t No7 34 M L NG +1-2/+1-2 ID No8 22 M L NG +3/+4 HLA-B27* Yes9 49 M R NG +3/+4 ID* Yes10 45 F R NG +1-2/+1-2 Colitis* associated Yes11 17 F L G +1-2/+1-2 ID*t No12 33 M L NG +1/+1 ID No13 19 M R NG +4/+4 HLA-B27* No14 52 F L NG +1-2/+1-2 ID* Yes

NG = non-granulomatous; G = granulomatous; ID = idiopathic.* Uveitis investigations performed.t Positive purified protein derivative with normal chest x ray.

performed by two experienced examiners (CT,ZS). Imaging was repeated during the courseof the disease when patient follow up allowed.A representative cross sectional image of the

ciliary body was used to quantify ciliary bodysize. The cross sectional area of the anteriorciliary body on the ultrasound biomicrographswas measured using a public domain imageprocessing and analysis program (NIH IMAGE1.60). On a Macintosh Quadra 840AV, an 8.5by 11 inch area consisting of five to sixultrasound biomicrographs were scanned at300 dpi and 20% scaling on a Microtek MSF-300 ZS flatbed colour/grey image scanner.Each scan was converted to a 324 kilobyteTIFF file which was imported into NIH IMAGE1.60. The scale was calculated using the selec-tion tool and set to 31 pixels per mm. Theanterior 2 mm of ciliary body was outlinedusing the free hand selection tool and its areawas calculated using the measurement com-mand. The external margin outlined extended2 mm along the uvea-scleral interface startinganteriorly at the scleral spur. The posteriormargin was constructed using a line perpen-dicular to the sclera. The internal and anteriormargins included the ciliary processes andanterior ciliary body face. Measurement ofeach micrograph was performed five times andrecorded as an average value in mm2.

Ciliary body sizes of the uveitic eyes beforetreatment were compared with the fellow,unaffected eyes, and with themselves at thesame meridian after treatment. Ciliary bodysizes of the uveitic eyes were correlated withthe clinical examination.

ResultsWe examined 14 consecutive patients with uni-lateral anterior uveitis. Mean patient age was35.2 (SD 13.7) years (range 16-55 years).There were eight men and six women. Six righteyes and eight left eyes were affected. The

Table 2 Cross sectional ciliary body area by group

Group No ofeyes Area (SD) (mm2) Range (mm2)

Uveitic eyes pre-treatment 14 2.45 (0.48) (2.03-3.66)Fellow eyes pre-treatment 14 1.55 (0.15) (1.36-1.92)Uveitic eyes post-treatment 11 1.62 (0.18) (1.40-1.91)Fellow eyes post-treatment 11 1.57 (0.15) (1.38-1.82)Normal control 15 1.53 (0.16) (1.26-1.77)

uveitis was classified as non-granulomatous in11 eyes (79%) and granulomatous in three eyes(21%). Four cases of non-granulomatous uvei-tis were considered recurrent by history. Theremainder of the patients with non-granulomatous uveitis and all of the patientswith granulomatous uveitis had no previoushistory of inflammation (Table 1).

Patients had varying degrees of inflamma-tion. Mean intraocular pressure was 13.2 (7.0)mm Hg (range 6-28 mm Hg) in the affectedeyes and 14.9 (3.7) (range 10-22 mm Hg) inthe fellow eyes. Slit-lamp biomicroscopy andgonioscopy suggested the presence of a uvealcyst in one eye due to a peripheral iriselevation. Treatment consisted of topical corti-costeroids and cycloplegics for all uveitic eyeswith the addition of a topical P blocker whenindicated to control intraocular pressure. Twopatients were treated with sub-Tenon's injec-tions of corticosteroid. One of these was alsotreated with oral corticosteroids. Laboratoryinvestigations were performed on 10 patients(71 %) and revealed HLA-B27 positivity in twopatients and a positive purified protein deriva-tive with normal chest x ray in three patients(Table 1).The cross sectional areas of the anterior cili-

ary body of the uveitic and the clinically unaf-fected, fellow eyes before treatment were 2.45(0.48) mm' and 1.55 (0.15) mm2, respectively(p = 0.0000; paired t test). Clinically unaf-fected eyes resembled our data base of normalcontrols (mean ciliary body area 1.53 (0.16)mm2, range 1.26-1.77 mm2) (Table 2). En-largement was limited to the pars plicataexcept for one patient (patient 13) with exten-sion to the pars plana. Eyes with greaterdegrees of cell (p = 0.01) and flare (p = 0.03)reactions tended to have larger cross sectionalciliary body areas. A ciliochoroidal effusion wasimaged in one uveitic eye and none of thefellow eyes.

Repeat UBM imaging was performed 1-6months after the initiation of treatment on 11patients. Three patients were lost to follow up.Resolution of the ciliary body enlargement orthe ciliochoroidal effusion was imaged in alltreated uveitic eyes (mean post-treatment crosssectional ciliary body area was 1.62 (0.18)mm' for the uveitic eyes and 1.57 (0.15) mm2for the fellow eyes (p = 0.40; paired t test)).The ciliary body was smaller in all uveitic eyesafter treatment when compared with them-selves before treatment (p = 0.0001; paired ttest). As expected, the fellow uninvolved eyedid not exhibit a change in cross sectional cili-ary body area during the course of the study (p= 0.57; paired t test)).

Epithelial cysts were imaged bilaterally infour patients and unilaterally in two patients(two fellow, non-uveitic eyes) before treatment.These cysts were located at the iridociliaryjunction (two patients), anterior ciliary body(two patients), or at both locations (twopatients). Cyst diameter ranged from 150 to1000 gm. Five of these patients had non-granulomatous and one had granulomatousuveitis. These cysts did not change in appear-ance during the course of the study.

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Ciliary body enlargement and cystformation in uveitis

Three new ciliary body cysts formed (that is,cysts in areas in which they were not previouslydetected) in three (27%) uveitic eyes duringthe follow up period. They occurred in twoeyes with cysts and in one eye without any pre-vious cysts whose fellow eye had one cyst. Twoof these eyes were diagnosed with HLA-B27associated uveitis and the other was diagnosedwith colitis associated uveitis in a patient whowas HLA-B27 negative. No new cysts formedin the fellow unaffected eyes during the followup period. Of the three newly formed cystsdemonstrated by UBM, two were iridociliarycysts, and one was an anterior ciliary body cyst.Their size ranged from 350 to 600 jim (Table3). There was no significant difference in thesize of the ciliary body or amount of inflamma-tion before treatment between those eyeswhich formed new cysts and those who didnot. In a comparable series of consecutivelyscanned normal patients, occult ciliary bodycysts were detected bilaterally in 2/15 (13%)patients.

REPRESENTATIVE CASESCase 1 (patient 2)A 55-year-old black woman with no past ocularor medical history presented with ciliary flush,pain, and photophobia in the right eye of 3days' duration. Slit-lamp examination revealed3+ cells and flare, an open angle, and scatteredposterior synechiae. The intraocular pressurewas 28 mm Hg in the right eye and 18 mm Hgin the left eye. There was no evidence of vitre-ous, retinal, or choroidal inflammation in theright eye. The left eye was unremarkable. UBMdemonstrated marked enlargement of the parsplicata compared with the fellow, unaffectedeye (Figs IA and B). Following medicaltherapy with topical prednisolone acetate 1%and cyclopentolate 1%, repeat imaging demon-strated resolution of the enlargement (Fig 1C).

Case 2 (patient 13)A 19-year-old white man with no past ocular or

medical history presented with conjunctivalinjection in the right eye of 4 days' duration.Slit-lamp examination demonstrated 2+ cellsand flare. Intraocular pressure was 6 mm Hgwith anterior vitreous cells and normal dilatedophthalmoscopy. Despite intensive topicaltherapy with prednisolone acetate 1%, theinflammation increased to 4+ cells and flareand he developed a spontaneous hyphaema.

Table 3 Ciliary body cysts

Figure 1 (A) Sagittal view of a normal ciliary body(arrow) in the unaffected eye. (B) Enlarged ciliary body(arrow) in the uveitic eye before treatment. (C) Resolutionof ciliary body enlargement (arrow) following treatment.

Uveitic eye (post-treatmentUveitic eye (pre-treatment) Fellow eye formation)

Patient Location Clock hour Size (plm) Location Clock hour Size (pm) Location Clock hour Size (,um)7 ACB 6:00 700 ACB 7:00 700 None NA NA

ACB 7:00 2508 ACB 6:00 700 ICJ 7:00 700 ICJ 9:00 500

ICJ 5:00 250 ICJ 10:00 1000ICJ 12:00 400 ICJ 12:00 300

10 ACB 9:00 1000 ICJ 4:00 200 ICJ 5:00 35011 None NA NA ICJ 9:00 300 None NA NA12 ICJ 3:30 800 ICJ 7:00 150 None NA NA

ICJ 11:00 80013 None NA NA ACB 3:00 250 ACB 9:00 600

ACB anterior ciliary body; ICJ = iridociliary junction; NA = not applicable.

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Figure 2 (A) Sagital view of massive enlargement of theciliary body (arrows) involving the pars plana (P) withassociated hyphaema (H) in the uveitic eye. The iris isvisible (I). (B) A new ciliary body cyst (arrow) hasformed after treatment has begun. (C) Transverse sectionshowing two small cysts (arrows) on the anterior ciliarybody in thefelow eye.

UBM demonstrated massive ciliary bodyenlargement with interzonular debris and a

partially contracted blood clot in the anteriorchamber (Fig 2A). No cysts were identified.Repeat UBM imaging after administration ofperiocular corticosteroids demonstrated reso-lution of the ciliary body swelling and theformation of a single large anterior ciliary bodycyst (Fig 2B). The fellow eye had two smallpars plicata cysts at 3 o'clock (Fig 2G). Thepatient was HLA-B27 positive.

Case 3 (patient 14)A 52-year-old Hispanic woman presented withrecurrent anterior uveitis in the left eye of 3days' duration. A similar episode had occurred2 years earlier. Slit-lamp examination revealed1-2+ cells and flare. The intraocular pressurewas 22 mm Hg and the angle was wide open.

Figure 3 (A) Sagittal view oflow lying ciliochoroidaleffusion (small arrows). (B) Resolution of the effiusionfollowing treatment.

The posterior segment was normal. UBMdemonstrated minimal ciliary body enlarge-ment with a shallow ciliochoroidal effusion inthe uveitic eye (Fig 3A). Repeat UBM aftertreatment demonstrated resolution of the effu-sion (Fig 3B).

DiscussionUveitis has diverse causes and systemic asso-ciations. The most widely used system ofclassification is based on the anatomicallocation of inflammation within the eye. Ante-rior uveitis, the most common form, can besubdivided clinically into iritis, iridocyclitis,and anterior cyclitis.'4 Very little is knownabout the pathology of acute anterior uveitis,with no clinical pathological studies in theacute phase having been conducted.' Ourstudy is the first to report in vivo alterations inciliary body anatomy associated with uveitis.

Ciliary body enlargement occurred in alleyes with uveitis and was directly related to theamount of inflammation. This most probablyrepresents stromal oedema caused by extrava-sation of plasma and infiltration of acuteinflammatory cells from vascular beds withinthe ciliary body. Consistent with the clinicalimpression of the location of inflammation,enlargement was limited to the pars plicata inall eyes except one. The exception was apatient (no 13) with a massively enlarged parsplicata, severe intraocular inflammation, and athickened pars plana.

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899Ciliary body enlargement and cystformation in uveitis

that eyes with inflammation have a predisposi-tion to cyst formation. We postulate that cystformation may occur as fluid enters theinterepithelial space of the posterior iris andciliary body. This may become more pro-nounced as ciliary body enlargement subsides,as evidenced by the formation of new cysts inthree of our patients.

In summary, UBM offers a new approach tothe evaluation of anterior uveitis. The responseto treatment can be evaluated objectively andtherapeutic efficacy can be more easily as-sessed. UBM has the potential to helpelucidate the pathophysiology and anatomicalchanges of this heterogeneous group of disor-ders.

Figure 4 (A) Typical cyst (arrow) at the iridociliaryjunction. (B) Cyst (E) in transverse section among theciliary processes (small arrows). The angle recess is visible(large arrow).

UBM imaged resolution of the ciliary bodyenlargement in all uveitic eyes and resolutionof a small ciliochoroidal effusion in one eyeafter treatment. In addition to detecting smallsubclinical effusions, UBM offers a new possi-ble quantitative tool in the evaluation of uveitis.UBM imaging on a video monitor permitted

visualisation of all the ciliary processes anddetection of cysts during each examinationwith accurate assessment of number and loca-tion. Ultrasonographically lucent areas consist-ent with a diagnosis of epithelial cysts were

found in both the uveitic and fellow non-uveitic eye. The majority of ciliary body cystswere bilateral and were located within the pos-

terior iris and ciliary body epithelium at the iri-dociliary junction or anterior ciliary body (Fig4). Although these cysts have been reported tooccur primarily without inflammation,"1"some cases have been described in eyes withinflammation.'516

Three uveitic eyes in the present studyshowed evidence of new cyst formation, thesignificance of which is unclear. It is possible

This work was supported in part by The Glaucoma Founda-tion, New York; awards in memory of Mary E and Alexander PHirsch (to CT) and Herbert Tenzer (to ZS), by The New YorkGlaucoma Research Institute, New York, The Fight For SightResearch Division of Prevent Blindness America, New York;and The New York Eye and Ear Infirmary Department of Oph-thalmology Research Fund.

Presented in part at the Annual Meeting of the AmericanAcademy of Ophthalmology, Chicago, Illinois, 14-15 Novem-ber 1993.The authors have no financial interest in the ultrasound

biomicroscope.

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