Cataract Surgery Outcomes in Uveitis

The Multicenter Uveitis Steroid Treatment Trial

H. Nida Sen, MD, MHS,1 Francis M. Abreu, BS,2 Thomas A. Louis, PhD,2 Elizabeth A. Sugar, PhD,2,3
Michael M. Altaweel, MD,4 Susan G. Elner, MD,5 Janet T. Holbrook, PhD, MPH,3
Douglas A. Jabs, MD, MBA,3,6 Rosa Y. Kim, MD,7 John H. Kempen, MD, PhD,8 for the Multicenter Uveitis Steroid
Treatment (MUST) Trial and Follow-up Study Research Group*

Purpose: To assess the visual outcomes of cataract surgery in eyes that received fluocinolone acetonide
implant or systemic therapy with oral corticosteroids and immunosuppression during the Multicenter Uveitis
Steroid Treatment (MUST) Trial.
Design: Nested prospective cohort study of patients enrolled in a randomized clinical trial.
Participants: Patients that underwent cataract surgery during the first 2 years of follow-up in the MUST Trial.
Methods: Visual outcomes of cataract surgery were evaluated 3, 6, and 9 months after surgery using log-
arithmic visual acuity charts. Change in visual acuity over time was assessed using a mixed-effects model.
Main Outcome Measures: Best-corrected visual acuity.
Results: After excluding eyes that underwent cataract surgery simultaneously with implant surgery, among
the 479 eyes in the MUST Trial, 117 eyes (28 eyes in the systemic, 89 in the implant group) in 82 patients un-
derwent cataract surgery during the first 2 years of follow-up. Overall, visual acuity increased by 23 letters from
the preoperative visit to the 3-month visit (95% confidence interval [CI], 17e29 letters; P < 0.001) and was stable
through 9 months of follow-up. Eyes presumed to have a more severe cataract, as measured by inability to grade
vitreous haze, gained an additional 42 letters (95% CI, 34e56 letters; P < 0.001) beyond the 13-letter gain in eyes
that had gradable vitreous haze before surgery (95% CI, 9e18 letters; P < 0.001) 3 months after surgery, making
up for an initial difference of
45 letters at the preoperative visit (95% CI,
56 to
34 letters; P < 0.001). Black
race, longer time from uveitis onset, and hypotony were associated with worse preoperative visual acuity (P <
0.05), but did not affect postsurgical recovery (P > 0.05, test of interaction). After adjusting for other risk factors,
there was no significant difference in the improvement in visual acuity between the 2 treatment groups (implant
vs. systemic therapy, 2 letters; 95% CI,
10 to 15 letters; P ¼ 0.70).
Conclusions: Cataract surgery resulted in substantial, sustained, and similar visual acuity improvement in
the eyes of patients with uveitis treated with the fluocinolone acetonide implant or standard systemic
therapy. Ophthalmology 2016;123:183-190 ª 2016 Published by Elsevier on behalf of the American Academy of
Ophthalmology.

Supplemental material is available at www.aaojournal.org.

Cataract is a common complication of uveitis. It can result
from inflammation as part of the disease process or from the
corticosteroids used to treat the inflammation. Cataract
surgery in the setting of uveitis differs from senile cataract
and can pose additional challenges and risks.1,2 Although
the outcomes of cataract surgery in uveitic eyes are not as
well studied as those in nonuveitic eyes, most studies sug-
gest poorer visual outcomes and more postoperative com-
plications among patients with uveitis. Furthermore, many
of these studies are weighted toward the results of cataract
surgery in patients with anterior uveitides.2e6
Preoperative control of inflammation is crucial for cata-
ract surgery in uveitic eyes. A systematic review of the
literature showed that eyes with controlled inflammation at
the time of cataract surgery had better visual outcomes.3 A
prospective study showed that eyes with active
inflammation within 3 months before cataract surgery
were more likely to have postoperative macular edema
and that a short perioperative course of oral
corticosteroids, started 2 days before surgery, significantly
reduced the incidence of postoperative macular edema.6
Hence, preoperative addition or increase in systemic
therapy, mainly corticosteroids, has become a standard
approach in cataract surgery for uveitic eyes.
An alternative approach to systemic therapy for treating
intermediate uveitis, posterior uveitis, and panuveitis is the
fluocinolone acetonide implant (Retisert; Bausch & Lomb,
Rochester, NY), which is designed to provide sustained,
steady-state levels of corticosteroids directly to the eye for
up to 3 years. In the Multicenter Uveitis Steroid Treatment

 2016 Published by Elsevier on behalf of the American Academy of Ophthalmology http://dx.doi.org/10.1016/j.ophtha.2015.09.022 183
ISSN 0161-6420/15

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 Ophthalmology Volume 123, Number 1, January 2016
Figure 1. Flowchart showing the selection of uveitic eyes with cataract
surgery during the Multicenter Steroid Treatment Trial for inclusion in
analysis. VA ¼ visual acuity.
(MUST) Trial, a randomized, clinical effectiveness trial of
implant therapy versus standard systemic therapy with oral
corticosteroids and immunosuppression for patients with
noninfectious intermediate uveitis, posterior uveitis, and
panuveitis, both the implant and systemic therapy
controlled the inflammation in the large majority of pa-
tients. Nevertheless, implant therapy resulted in inactive
inflammation in a greater proportion of eyes than did
systemic therapy.7 Because cataracts occurred in both
treatment groups, the MUST Trial provides the
opportunity to compare the outcomes of cataract surgery
in uveitic eyes with fluocinolone acetonide implants with
those of patients treated with systemic corticosteroids and
immunosuppression.
Methods
Eligibility
Patients included in this study were participants in the MUST Trial,
a randomized, comparative effectiveness clinical trial comparing
the fluocinolone acetonide intraocular implant with standard sys-
temic therapy (systemic corticosteroids and immunosuppressive
medications) for the treatment of noninfectious, recently active
intermediate uveitis, posterior uveitis, or panuveitis (clinical-
trials.gov identifier, NCT00132691). The study enrolled 255 pa-
tients at 23 clinical centers in the United States (21 centers), United
Kingdom, and Australia. The protocol was approved by the insti-
tutional review board of each center, and all participants provided
written informed consent. The study complied with the Health
Insurance Portability and Accountability Act and adhered to the
tenets of the Declaration of Helsinki.7,8 Data on best-corrected
visual acuity and a detailed ocular and medical history were
collected at 3-month intervals for 2 years.
Uveitic eyes that underwent cataract surgery during follow-up
were eligible for inclusion in this study unless the surgery was per-
formed before or concurrent with implant surgery (Fig 1). Eyes that
underwent concurrent cataract and implant surgery were excluded
because of possible interference of implant surgery and its
complications with cataract surgery-related outcomes. Visit win-
dows were structured for the purpose of this analysis into a
184
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preoperative visit that occurred within 6 months of the date of surgery
(
6 to 0 months) and postsurgical visits that occurred at 3, 6, and 9
months after surgery with windows of 0 to 4 months, 4 to 7 months,
and 7 to 10 months, respectively. In addition, eyes that did not have a
preoperative visual acuity measurement or a postsurgical visual acuity
measurement within 10 months after surgery were excluded.
Outcomes
The primary outcome of the current study was best-corrected visual
acuity, measured using logarithmic visual acuity charts8,9 accord-
ing to a standardized protocol. Secondary outcomes included bi-
nary categorizations of visual acuity patterns. The change from the
preoperative to the first available postoperative visit was defined in
2 ways. For the purposes of this study, we considered a 5-letter
improvement or more or a visual acuity outcome of 20/40 or
better to be clinically meaningful. We first calculated the propor-
tion of eyes with an improvement based on the number of letters (5
or 10 letters of improvement), and then the proportion of eyes that
improved to 20/40 or better at the first postoperative visit was
analyzed. The proportion of eyes with visual acuity of 20/40 or
better at the first postoperative visit also was considered.
Statistical Analyses
Analyses were conducted based on the treatment being received at
the time of the presurgical visit. The Kruskal-Wallis rank-sum test
and the Fisher exact test were used to compare patient-level
characteristics of the 2 therapies for eligible patients at the pre-
operative visit. A linear logistic (binary attribute) or multinomial
(multicategory attribute) mixed-effects model with a patient-level
random effect to adjust for between-eye correlation was used to
compare preoperative eye-level characteristics between therapies.
To model visual acuity over time, a means mixed-effects model
that included terms for treatment, visit, and treatment-by-visit
interaction was specified and estimated via maximum likelihood.
A patient-level random intercept and a first-order autoregressive
covariance structure for the within-eye repeated measurements
were included to introduce between-eye correlation (via the
random intercept) and longitudinal within-eye correlation (the first-
order autoregressive component).
The association of other risk factors was assessed by adding
them to the base model structure as follows: a main effect to assess
the impact on baseline visual acuity and an interaction term with
time to assess the impact on change in visual acuity after surgery.
Secondary outcomes were modeled by logistic regression esti-
mated via generalized estimating equations that account for the
between-eye correlation for individuals with bilateral cataract
surgery. Inability to grade vitreous haze was used as a surrogate for
cataract severity. The risk factors considered included both indi-
vidual characteristics (age, race, gender, uveitis location, presence
of systemic disease) and preoperative eye-specific characteristics
(disease duration, intraocular pressure, inability to grade vitreous
haze). Robust standard errors were computed for all models. Sta-
tistical analyses were performed using SAS software version 9.3
(SAS Inc, Cary, NC), Stata 12 software (StataCorp LP, College
Station, TX), and R software version 3.0.1 (The R project for
Statistical Computing; available at: http://www.r-project.org/).
Results
From the 479 eyes with uveitis of the 255 individuals enrolled in
the MUST Trial, a total of 117 eyes from 82 patients met the
criteria for inclusion in the cataract study during the first 2 years of
follow-up in the MUST Trial (Fig 1). A total of 28 eyes (24%)
received systemic therapy and 89 eyes (76%) received implant
 Sen et al 
Cataract Surgery Outcomes in Uveitis

Table 1. Characteristics of Patients and Eyes Undergoing Cataract Surgery in the Multicenter Uveitis Steroid Treatment Trial

Treatment Group
Overall Systemic Implant P Value*
Patient characteristics
Participants, no. (%) 82 22 (27) 60 (73)
Demographics
Age at preoperative visit (yrs), median (IQR) 46 (31e53) 53 (38e58) 44 (31e51) 0.20
Male gender, no. (%) 27 (33) 5 (23) 22 (37) 0.29
Black race, no. (%) 15 (18) 3 (14) 12 (20) 0.75
Clinical characteristics at the time of randomization in the MUST Trial
Posterior uveitis or panuveitis, no. (%) 52 (63) 12 (55) 40 (67) 0.44
Systemic disease, no. (%) 22 (27) 4 (18) 18 (30) 0.40
Eye characteristics
Eligible eyes, no. (%) 117 28 (24) 89 (76)
Time since uveitis onset at the preoperative visit (yrs),z median (IQR)y 2 (1e5) 1 (0e3) 2 (1e5) 0.18z
Preoperative visual acuity (standard letters), no. (%)
Median (IQR) 56 (25e69) 43 (5e59) 60 (38e72) 0.09
20/40 or better 29 (25) 5 (18) 24 (27) 0.33
Worse than 20/100 50 (43) 18 (64) 32 (36) 0.031
20/200 or worse 33 (28) 12 (43) 21 (24) 0.09
Preoperative vitreous haze ungradable, no. (%) 26 (22) 12 (43) 14 (16) 0.003
Preoperative intraocular pressure (mmHg), no. (%)y
Median (IQR) 18 (14e23) 16 (13e20) 18 (15e24) 0.037
7 5 (4) 3 (11) 2 (2)
8e23 84 (72) 21 (75) 63 (72)
24e29 19 (16) 2 (7) 17 (19)
30 8 (7) 2 (7) 6 (7)

IQR ¼ interquartile range (i.e. the 25th to 75th percentile); MUST ¼ Multicenter Uveitis Steroid Treatment.
*Unless otherwise specified, P values compare the distribution of all primary categories excluding missing values.
y
Missing values: 1 preoperative intraocular pressure observation missing (1%) from implant group, and 2 observations missing time since uveitis at
the preoperative visit in the implant group (2%).
z
Based on a log transformation of time since uveitis onset at the preoperative visit.

therapy. Two eyes receiving systemic therapy and 15 of those
receiving implant therapy originally were randomized to receive
the other treatment. The most common reasons for exclusion
included aphakia or pseudophakia at enrollment (n ¼ 202 eyes),
no surgery during follow-up (n ¼ 113), or concurrent cataract
and implant surgery (n ¼ 22).
Demographic characteristics at the preoperative visit were
similar between treatment groups, with 33% of patients being men,
18% of patients being black, and a median age of 46 years overall
(Table 1). Fifty-two patients (63%) had posterior uveitis or pan-
uveitis, with a nonsignificantly higher proportion in the implant
group (67%) compared with the systemic group (55%). Preopera-
tive visit visual acuities for eyes in the implant group were better
than those in the systemic therapy group (median, 60 vs. 43 letters,
respectively; P ¼ 0.090), but this difference did not achieve con-
ventional statistical significance. However, the proportion of eyes
with visual acuity worse than 20/100 was significantly higher in
the systemic group than in the implant group (64% vs. 36%,
respectively; P ¼ 0.031). Time since uveitis onset (or duration of
uveitis) was similar between the 2 treatment groups, with an
overall median of 2 years (interquartile range, 1e5 years). The
proportion of eyes with ungradable vitreous haze at the preop-
erative visit was significantly higher in the systemic treatment
group (43% vs. 16%; P ¼ 0.003; Table 1). Preoperative
intraocular pressure was within the normal range in both
groups, but the median was 2-mmHg higher for eyes in
the implant group, a magnitude that was statistically significant
(P ¼ 0.037), but not clinically meaningful.
Cataract surgery included intraocular lens placement in the
overwhelming majority of eyes (113 eyes [97%]); the other 4 eyes
(3%) were left aphakic. There was no difference by treatment
group. In the implant group, 86 eyes (97%) had an intraocular lens
placed, and in the systemic therapy group, 27 eyes (96%) had an
intraocular lens placed (P ¼ 0.91).
Overall, visual acuity improved by 23 letters (95% confidence
interval [CI], 18e29 letters; P < 0.001) from the preoperative visit
to the 3-month postoperative visit. The visual acuity was stable
thereafter with an additional 2 letters at 6 months (95% CI,
0 to 4
letters; P ¼ 0.05) that vanished by 9 months (P ¼ 0.62). This
pattern of improvement at 3 months that remained stable through 9
months was seen in both treatment groups (Fig 2). The point
estimate of improvement was larger for eyes receiving systemic
therapy (29 letters; 95% CI, 17e43 letters; P < 0.001) as
compared with eyes receiving implant therapy (21 letters; 95%
CI, 16e27 letters; P < 0.001). However, the difference between
the groups in visual improvement was not statistically significant
(mean,
9 letters for implant vs. systemic therapy; 95% CI,
23
to 6 letters; P ¼ 0.24).
In the multivariate model, a number of factors were associated
with worse visual acuity at the preoperative visit (Table 2). Eyes
that had ungradable preoperative vitreous haze had a
preoperative visual acuity that was 45 letters worse (
45 letters)
than in eyes that were gradable (95% CI,
56 to
34 letters; P
< 0.0001); eyes of black patients had a preoperative visual
acuity that was 12 letters worse than those of nonblack patients
(95% CI,
22 to
2 letters; P ¼ 0.021), and preoperative
hypotony (intraocular pressure, 7 mmHg) was associated with
a visual acuity of 8 letters worse as compared with eyes with
normal intraocular pressure (8e23 mmHg). For each decade
since uveitis diagnosis, there was a 4.7-letter worse preoperative

185

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 Ophthalmology Volume 123, Number 1, January 2016
Figure 2. Mean visual acuity over time for eyes with cataract surgery
during the Multicenter Steroid Treatment Trial stratified by treatment
(implant [grey] vs. systemic [black] therapy). The 95% confidence intervals
are included for each treatment group at each interval.
visual acuity (95% CI,
9 to
0.4 letters; P ¼ 0.033). After
adjusting for other risk factors, there was no significant difference
in the preoperative visual acuity for the 2 treatment groups (implant
vs. systemic therapy: median, 6 letters; 95% CI,
4 to 15 letters;
P ¼ 0.22).
Only the ability to grade preoperative vitreous haze was asso-
ciated significantly with the amount of improvement in visual
acuity after cataract surgery (Table 2). For eyes with gradable
vitreous haze, visual acuity improved by a mean of 13 letters
from the preoperative visit to the 3-month postoperative visit
(95% CI, 9e18 letters; P < 0.001) and showed a significant
additional gain at 6 months (mean, 3 letters; 95% CI, 1e4 letters;
P ¼ 0.001) that had vanished by 9 months (P ¼ 0.52). Eyes that
were not gradable for vitreous haze at the preoperative visit had an
additional mean improvement of 42 letters (95% CI, 35 to
56
letters; P < 0.001) from the preoperative visit to the 3-month
postoperative visit beyond that observed with gradable vitreous
haze, for a mean total improvement of 55 letters. The difference in
improvement was such that eyes with preoperative ungradable
vitreous haze had postoperative visual acuities that were not sta-
tistically or clinically significantly different from those with grad-
able preoperative vitreous haze (mean,
3 letters; 95% CI,
12 to
7 letters; P ¼ 0.55). After adjusting for other risk factors, there was
no significant difference in the improvement in visual acuity be-
tween the 2 treatment groups (implant vs. systemic therapy: mean,
2 letters; 95% CI,
10 to 15 letters; P ¼ 0.70).
Overall, most eyes improved by a clinically meaningful amount
between the preoperative and first postoperative visit (Table 3).
Ninety-two eyes (79%) had an improvement of 5 letters or more
and 77 eyes (67%) had an improvement of 10 letters or more. In
fact, 72 eyes (62%) had a postoperative visual acuity of 20/40 or
better, including 45 eyes (63%) that improved from worse than 20/
40 to 20/40 or better, all of whom had at least a 5-letter gain. Very
few eyes experienced a 5-letter or more decline in visual acuity; 5
eyes (4%) had a decline of 5 letters or more and only 3 eyes (3%)
had a decline of 10 letters or more.
Similar to what was seen in the analysis of mean change in
visual acuity, eyes with ungradable vitreous haze at the
186
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preoperative visit were more likely to experience postoperative
visual acuity improvement by 10 letters or more (odds ratio [OR],
7.9 letters; 95% CI, 1.8e35.1 letters; P ¼ 0.007) and a post-
operative visual acuity of 20/40 or better regardless of preoperative
visual acuity (OR, 1.7 letters; 95% CI, 1.1e2.7 letters; P ¼ 0.03).
There was no significant difference in the probability of post-
operative improvement in vision by 5 letters or more, 10 letters or
more, or having postoperative visual acuity of 20/40 or better for
the 2 treatment groups (P > 0.49; Table 3). None of the other
patient or eye characteristics were associated significantly with
any of the postoperative improvement outcomes. However, there
was a suggestion that having posterior uveitis or panuveitis at
enrollment in the MUST Trial was associated with a lower
probability of a 5- or 10-letter improvement (OR, 0.3; 95% CI,
0.1e1.1; P ¼ 0.060; and OR, 0.4; 95% CI, 0.2e1.1; P ¼ 0.07,
respectively). Because of the small number of eyes with a
decline, we were unable to evaluate risk factors associated with a
loss of vision.
Discussion
Cataract is among the most common structural complica-
tions of uveitis and its treatment with corticosteroids, and
cataract surgery is among the most common surgical pro-
cedures performed on patients with uveitis. Several studies
have reported that substantial visual gain occurs in most
uveitic eyes after cataract surgery.2e4,10e14 Although cata-
ract is a well-recognized occurrence with the fluocinolone
acetonide implant and cataract surgery is needed in more
than 90% of eyes by 3 years after implantation,15 the MUST
Trial provided the first opportunity to compare the outcomes
of cataract surgery in eyes with the implant with those of
patients treated with systemic therapy. The current study
showed statistically significant, clinically meaningful, and
sustained (for up to 9 months after surgery) improvement
in visual acuity of similar magnitude after cataract surgery
in both eyes treated with systemic therapy and those
treated with the fluocinolone acetonide implant. Overall,
62% of eyes achieved a visual acuity of 20/40 or better
after surgery. This success proportion is lower than that
reported for uncomplicated cataract surgery in the general
public (96%),16 but similar to that reported in other
studies of uveitic cataract surgery.3
In a meta-analysis of the outcomes of cataract surgery,
Mehta et al3 estimated that the overall percent of eyes with
uveitis achieving 20/40 or better postoperative visual acuity
was 68% and that anterior approaches, intraocular lens
placement, nonsilicone lenses, and operating on eyes with
inactive uveitis were associated with better outcomes.
Uveitis class was not evaluated systematically, but Fuchs
heterochromic uveitis seemed to respond better than other
types of uveitis; intermediate uveitis seemed to have a
similar success rate to the overall rate; and the one
panuveitis evaluated, Behçet’s disease, had worse
outcomes. In this regard, there was a suggestion from our
data that posterior uveitis and panuveitis may show a
worse response than intermediate uveitis. Such a result
would not be surprising because patients with posterior
uveitis are more likely to encounter permanent structural
damage that may limit visual improvement. Because the
MUST Trial enrolled patients with only intermediate
 Sen et al 
Cataract Surgery Outcomes in Uveitis

Table 2. Adjusted* Risk Factors Affecting Visual Acuity at the Preoperative Visit and Affecting the Preoperative to Postoperative Visit
Change in Visual Acuity in the Multicenter Uveitis Steroid Treatment Trial

Preoperative Visual Acuity

Estimated Mean Difference at Preoperative Visit,
Characteristics Letters (95% Confidence Interval) P Value
Treatment
Systemic Reference
Implant 5.5
3.3 to 14.4 0.22
Race
Nonblack Reference
Black
12.0
22.1 to
1.8 0.021
Time from uveitis onset at preoperative visit
4.7
9.0 to
0.4 0.033
(10 yrs), centered at 2 yrs
Preoperative intraocular pressure (mmHg)
7
7.6
14.0 to
1.0 0.022
8e23 Reference
24e29
5.6
16.4 to 5.2 0.31
30 9.1
1.6 to 19.8 0.096

Change from Preoperative to Postoperative Visual Acuity

Mean Difference from Preoperative to Postoperative
Visits, Letters (95% Confidence Interval) P Value
y
Eyes with gradable preoperative vitreous haze
Preoperative visit Reference
3 mos 13.4 9.7e17.1 <0.001
6 mos 15.9 12.6e19.2 <0.001
9 mos 15.4 11.7e19.0 <0.001
Eyes with ungradable preoperative vitreous haze
Preoperative visit Reference
3 mos 55.4 42.9e67.9 <0.001
6 mos 58.0 45.4e70.6 <0.001
9 mos 57.4 44.7e70.1 <0.001

*Adjusted for all factors simultaneously.

y
The association of preoperative vitreous haze with preoperative visual acuity was significantly different from its association with postoperative visual acuity
(P < 0.001).

uveitis, posterior uveitis, or panuveitis, its results ay not be
comparable directly with those of series including eyes with
anterior uveitis. Nevertheless, the proportion of eyes with a
postoperative visual acuity of 20/40 or better in the MUST
Trial is on the same order as that in the meta-analysis.
The level of vision before cataract surgery differed be-
tween the 2 treatment groups, and it was likely that eyes in the
systemic group had worse cataracts at the time of surgery.
Eyes receiving systemic therapy were significantly more
likely to have a preoperative visual acuity worse than 20/100
and, assuming that inability to grade the vitreous haze is a
marker for denser cataract, worse cataracts. Reasons for this
difference are unknown, but it is possible that ophthalmolo-
gists were likely to operate sooner on eyes treated with
implant therapy because cataract surgery is an expected and
nearly universal complication of implant therapy.7,15,17 It is
also possible that eyes with more severe cataracts in the
implant group had simultaneous cataract and implant surgery
and were excluded from this study. Nevertheless, there was no
significant difference in the visual improvement between the 2
treatment groups, even after adjusting for other risk factors.
Sheppard et al17 evaluated cataract outcomes in uveitic eyes
that received the fluocinolone acetonide implant and compared
them with those of fellow, nonimplanted eyes. They reported
that eyes undergoing cataract surgery after the implantation
had a better visual acuity gain and less postoperative
inflammation than the fellow eyes, which were untreated or
managed with regional corticosteroid injections.15 No details
were given in this article about the duration of inactive
disease or preoperative regimens in the nonimplant group,
whereas given the duration of effect of the implant, these
eyes were receiving preoperative corticosteroid therapy
comparable with that resulting from systemic therapy. In this
regard, the MUST results suggest that eyes with intermediate
uveitis, posterior uveitis, or panuveitis will have similar
postoperative visual improvement whether the eye has been
treated with an implant or with systemic therapy.
Although black patients and eyes with hypotony were
associated with poorer preoperative visual acuity, they were
not associated with any worse likelihood of visual
improvement after cataract surgery. The risk factors that
were associated with lower preoperative visual acuity (black
race, disease duration, hypotony) are known risk factors for
poorer visual acuity in eyes with uveitis.18e20 Longer dis-
ease duration is known to be associated with poorer out-
comes and more structural complications,18,21,22 and
hypotony, which likely is reflective of the chronicity and
severity of the underlying disease, has been associated with

187

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 Ophthalmology Volume 123, Number 1, January 2016

Table 3. Risk Factors for Visual Acuity Improvement in Eyes Undergoing Cataract Surgery in the Multicenter Uveitis Steroid Treatment
Trial

Postoperative Visual
‡5-Letter Improvement ‡10-Letter Improvement Acuity 20/40 or Better
(n [ 117) (n [ 115)* (n [ 117)
95% Confidence 95% Confidence P Odds 95% Confidence P
Odds Ratio Interval P Value Odds Ratio Interval Value Ratio Interval Value
Patient characteristics
Demographics
Age at preoperative visit (yrs) 1.0 0.9e1.1 0.47 1.0 0.9e1.1 0.19 1.0 0.9e1.1 0.13
Gender
Female Ref Ref Ref
Male 1.2 0.4e3.1 0.76 0.9 0.4e2.1 0.79 1.7 0.7e4.1 0.24
Race
Nonblack Ref Ref Ref
Black 0.9 0.3e2.8 0.82 1.3 0.4e4.0 0.59 0.7 0.3e2.1 0.57
Clinical characteristics at the time
of randomization in the MUST Trial
Uveitis class
Intermediate uveitis Ref Ref Ref
Posterior uveitis or panuveitis 0.3 0.1e1.1 0.06 0.4 0.2e1.1 0.07 1.0 0.4e2.4 0.98
Systemic disease
No Ref Ref
Yes 1.0 0.3e2.8 0.96 1.0 0.4e2.6 0.97 1.6 0.6e4.1 0.34
Eye characteristics
Treatment
Systemic Ref Ref Ref
Implant 1.4 0.5e4.0 0.49 1.0 0.5e2.5 0.99 1.36 0.6e3.3 0.49
Time from uveitis onset at preoperative 1.0 0.9e1.1 0.96 1.0 0.9e1.1 0.91 1.0 0.9e1.1 0.36
visit (yrs), centered at 2 yrs
Preoperative intraocular pressure (mmHg)
7 1.3 0.1e14.2 0.80 2.3 0.2e22.4 0.47 0.2 0.0e1.3 0.09
8e23 Ref Ref Ref
24e29 1.4 0.4e5.4 0.62 1.5 0.5e4.6 0.51 1.1 0.4e3.3 0.80
30 0.7 0.1e4.0 0.74 1.2 0.2e6.3 0.86 0.9 0.2e4.2 0.93
Preoperative vitreous haze
Gradable Ref Ref Ref
Ungradable 3.7 0.8e16.7 0.08 7.9 1.8e35.1 0.007 1.7 1.1e2.7 0.03

MUST ¼ Multicenter Uveitis Steroid Treatment; Ref ¼ reference.

*Two eyes with a preoperative visual acuity of 89 letters, which precluded a 10-letter improvement, were excluded.

poorer visual acuity in patients with uveitis.19,21,22 Although
these factors were associated with poorer overall vision,
none of them had an impact on improvement in visual acuity
after surgery (P > 0.05, test of interaction). The only
characteristic associated with better gains in vision after
surgery was ungradable vitreous haze before surgery. As
noted above, it is likely that ungradable vitreous haze before
surgery was a marker for denser and worse cataract,
resulting in worse visual acuity before surgery and bigger
gains in acuity at the postoperative visits.
The typical recommendation is to defer cataract surgery in
uveitic eyes until the uveitis has been inactive for a minimum
of 3 months before surgery and to pretreat patients with sys-
temic corticosteroids briefly before cataract surgery and for a
short time after surgery. A systematic review and meta-analysis
of the literature found that active uveitis at the time of cataract
surgery was associated with poorer outcomes. A prospective
study of cataract surgery6 demonstrated that active uveitis
within 3 months before cataract surgery and failure to use
perioperative systemic corticosteroids each were associated
with worse outcomes and evidenced by more macular
edema. Unfortunately, the follow-up schedule and visit win-
dows in this study (in which the preoperative visit could be as
much as 6 months before surgery) precluded the evaluation of
the effect of inactive uveitis in the 3 months before surgery.
Similarly, the surgical data collection did not include infor-
mation on the use of perioperative oral corticosteroids.
Our study is limited by the relatively small number of
eyes in the systemic treatment group. We were unable to
measure the severity of cataract directly and instead used a
surrogate (inability to grade vitreous haze) to attempt to
account for the impact of severity. The large majority of
eyes showed an improvement in visual acuity, which limited
our ability to perform multivariate analyses of risk factors
related to visual acuity threshold. Nearly all eyes had
placement of an intraocular lens, limiting any power to
evaluate the effect of aphakia. Finally, the small number of
eyes with a decline made it impossible to evaluate for risk
factors related to decline. Nevertheless, our study suggested
that patients with intermediate uveitis, posterior uveitis, or

188

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 Sen et al 
Cataract Surgery Outcomes in Uveitis
panuveitis show similar improvements in visual acuity after
cataract surgery, regardless whether the uveitis was treated
with the fluocinolone acetonide implant or with systemic
therapy with oral corticosteroids and immunosuppression.
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Footnotes and Financial Disclosures
Originally received: June 24, 2015.
Final revision: September 9, 2015.
Accepted: September 15, 2015.
Available online: October 20, 2015. Manuscript no. 2015-1055.
1
National Eye Institute, National Institutes of Health, Bethesda, Maryland.
2
Department of Biostatistics, The Johns Hopkins University Bloomberg
School of Public Health, Baltimore, Maryland.
3 Treatment Research Group is available at www.aaojournal.org.
Department of Epidemiology, The Johns Hopkins University Bloomberg
School of Public Health, Baltimore, Maryland.
4
Department of Ophthalmology, University of Wisconsin School of
Medicine and Public Health, Madison, Wisconsin.
5
Department of Ophthalmology, Kellogg Eye Center, University of
Michigan, Ann Arbor, Michigan.
6
Departments of Ophthalmology and Medicine, Icahn School of Medicine
at Mount Sinai, New York, New York.
7 Supported by the National Eye Institute, National Institutes of Health,
Retina Consultants of Houston, Houston, Texas; Blanton Eye Institute,
Houston Methodist Hospital, Houston, Texas; and the Department of
Ophthalmology, Weill Cornell Medical College, New York, New York.
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outcome after cataract surgery in patients with uveitis.
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cataract outcomes in patients with noninfectious posterior
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19. Sen HN, Vitale S, Gangaputra SS, et al. Periocular cortico-
steroid injections in uveitis: effects and complications.
Ophthalmology 2014;121:2275–86.
20. Maini R, O’Sullivan J, Reddy A, et al. The risk of complica-
tions of uveitis in a district hospital cohort. Br J Ophthalmol
2004;88:512–7.
21. Sen HN, Drye LT, Goldstein DA, et al; for the Multicenter
Uveitis Steroid Treatment (MUST) Trial Research Group.
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Steroid Treatment (MUST) trial. Ocul Immunol Inflamm
2012;20:104–12.
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8
Department of Ophthalmology and the Center for Clinical Epidemiology
and Biostatistics, Department of Biostatistics and Epidemiology, The
University of Pennsylvania Perelman School of Medicine, Philadelphia,
Pennsylvania.
Presented at: American Academy of Ophthalmology Annual Meeting,
Chicago, IL, October 2014.
*A complete listing of the members of the Multicenter Uveitis Steroid
Financial Disclosure(s):
The author(s) have made the following disclosure(s): D.A.J.: Consultant -
Santen (Osaka, Japan); Data and Safety Monitoring Committee
Applied
Genetic Technologies Corporation (Alachua, FL)
J.H.K: Consultant - AbbVie (North Chicago, IL); Alcon (Fort Worth, TX);
Allergan (Irvine, CA) Can-Fite (Peta-Tikva, Israel); Clearside (Alpharetta,
GA); Lux Biosciences (Jersey City, NJ); Roche (Basel, Switzerland) Xoma
(Berkeley, CA)
Bethesda, Maryland (Collaborative Agreement nos.: U10EY014655
[D.A.J.], U10EY014660 [J.T.H.], and U10EY014656 [M.M.A.]); and the
National Eye Institute Intramural Research Program (H.N.S.) (Bethesda,
189
 Ophthalmology Volume 123, Number 1, January 2016
MD). Bausch & Lomb (Rochester, NY) provided support to the study in the
form of donation of fluocinolone implants for patients randomized to
implant therapy who were uninsured or otherwise unable to pay for im-
plants, or who were located at a site where implants could not be purchased
(e.g., the United Kingdom). Additional support was provided by Research
to Prevent Blindness, Inc., New York, NY; the Paul and Evanina Mackall
Foundation (Chicago, IL); and the Lois Pope Life Foundation (Delray
Beach, FL). A representative of the National Eye Institute participated in
the conduct of the study, including the study design; collection, manage-
ment, analysis, and interpretation of the data; and review and approval of
this manuscript. The sponsor or funding organization had no role in the
design or conduct of this research.
Pictures & Perspectives
190
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For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
Author Contributions:
Conception and design: Kempen, Jabs, Abreu, Louis, Sugar, Sen
Analysis and interpretation: Kempen, Jabs, Abreu, Louis, Sugar, Sen
Data collection: Sen, Abreu, Louis, Sugar, Altaweel, Elner, Holbrook, Jabs,
Kim, Kempen
Obtained funding: none
Overall responsibility: Kempen, Jabs, Sen
Abbreviations and Acronyms:
CI ¼ confidence interval; IQR ¼ Interquartile range; MUST ¼ Multicenter
Uveitis Steroid Treatment; OR ¼ odds ratio.
Correspondence:
H. Nida Sen, MD, MHS, National Eye Institute, National Institutes of
Health, 10 Center Drive, 10N109, Bethesda, MD 20892. E-mail: senh@nei.
nih.gov.
Histologic Changes in a Squamous Cell Carcinoma of
Conjunctiva Refractive to Interferon-a2b
A 74-year-old man presented with a limbal mass (Fig 1A),
found by incisional biopsy to be full-thickness conjunctival
intraepithelial neoplasia (squamous cell carcinoma in situ)
(Fig 1B, arrow). No significant inflammation was present at
this stage. Despite 3 months of topical interferon a-2b ther-
apy, the lesion enlarged (Fig 1C). The mass was surgically
excised, and histopathology revealed progression to invasive
squamous cell carcinoma with marked pleomorphism,
numerous mitotic figures (Fig 1D, arrow), foreign body giant
cells (Fig 1D, asterisk), and dyskeratosis. Although there was
superficial necrosis (Fig 1D, star), the deeper tumor appeared
viable.
MARIA E. RODRIGUEZ, MD
CHRISTOPHER K. BURRIS, MD
NOAH B. SAIPE, MD
Department of Ophthalmology and Visual Sciences, University of
Wisconsin e Madison, Wisconsin