Study Population

Medical records of 108 patients with JIA-associated uveitis (International Classification of Disease [ICD] codes: 714.30 + 364.XX) seen between July 1984 and June 30, 2014 in the Division of Ocular Immunology at the Wilmer Eye Institute, Johns Hopkins Hospital, were identified. Diagnoses were based on review of case history and ophthalmologic examination by a uveitis specialist with ancillary testing guided by clinical findings.

Data Collection

Data were collected by chart review and entered into a standardized database. Data included demographic features (age, sex, and race), past history of arthritis, past history of uveitis, anatomic location of the uveitis as defined by the Standardization of Uveitis Nomenclature (SUN) Working Group, results of diagnostic testing, and medications (doses and routes) at each clinic visit. Ophthalmic findings at each visit included visual acuity, intraocular pressure (IOP), slit-lamp examination, grade of inflammation in the anterior chamber and in the vitreous by SUN criteria, and dilated fundus findings.

Main Outcome Measures

The prevalence of hypotony (defined as IOP <5 mm Hg) and low IOP (defined as IOP ≥5 mm Hg but lower than 8 mm Hg) at presentation and the incidence of these conditions during follow-up were assessed retrospectively. To calculate incidence rates of these outcomes, eyes with hypotony and low IOP were compared with eyes with IOP ≥8 mm Hg in follow-up data. The following variables were assessed for potential association with hypotony and low IOP: age at presentation, age at the time of uveitis diagnosis, sex, race, visual acuity at presentation, any prior intraocular surgery, prior cataract surgery, prior glaucoma surgery, prior vitrectomy, inflammatory activity in the eye (anterior chamber cell, anterior chamber flare, vitreous cell, vitreous haze), anatomic location of the uveitis, duration of uveitis, presence of other structural ocular complications of uveitis (band keratopathy, posterior synechiae, cataract, epiretinal membrane, macular edema, optic nerve edema), and the treatment at presentation (topical corticosteroids, topical IOP lowering drops, immunosuppressive drug therapy, and/or oral corticosteroids). The development of new-onset complications among eyes affected with uveitis was noted on clinical examination. The development of new-onset cataract was defined as the presence of 1+ nuclear sclerosis, 1+ cortical change, or trace posterior subcapsular change seen on clinical examination in an eye in which no cataract had been reported on prior visits.

Statistical Analysis

Statistical analysis was performed using Stata statistical software (version 10.0, 2007; Stata Corporation, College Station, Texas, USA). Frequencies and medians of demographic variables were tabulated for patients/eyes and compared using χ ² test and t test for categorical and numerical data, respectively. Incidence rates for ocular complications were calculated as the number of events divided by the number of eye-years (EY) of the at-risk eyes. At-risk eyes included all eyes that were free of each respective outcome at presentation with at least 1 follow-up visit in our clinic. The 95% confidence intervals (CI) were calculated for the estimated incidence rates of ocular complications. For risk factor analyses regarding prevalence of hypotony or low IOP among eyes at cohort entry, crude and adjusted odds ratios (aOR) were calculated using univariate and multivariate logistic regression. Time-updated univariate and multivariate Cox proportional-hazards models were used to assess the potential risk factors for developing new-onset hypotony or low IOP among patients with JIA-associated uveitis and crude and adjusted hazard ratios reported. P values were 2-sided and nominal, with a value < .05 being considered as statistically significant.

Characteristics of the Study Population at Presentation

One hundred and eight patients (196 eyes) with JIA-associated uveitis were identified. The majority of patients were female (73%, n = 79) and white (82%, n = 85). The median age at onset of uveitis was 6 years (range, 0.5–35 years), with a median duration of uveitis prior to presentation of 4 years (range, −2.0 to 45.4 years). Of the 108 patients with JIA-associated uveitis, 12 (11.1%) (20 eyes, 10.2%) had documented history of hypotony prior to presentation. Ten patients (9.3%) (14 eyes, 7.1%) presented with hypotony, and 4 patients (3.7%) (5 eyes, 2.6%) presented with low IOP. Four patients (3.7%) presented with bilateral hypotony and 1 patient presented with bilateral low IOP.

Risk Factors for Hypotony at Presentation

Based on IOP at presentation, eyes were categorized as having hypotony (n = 14 eyes, median IOP = 1.5; range = 0–4 mm Hg), low IOP (n = 5 eyes, median IOP = 7; range = 5–7 mm Hg), or IOP ≥8 mm Hg (n = 177 eyes; median IOP = 15; range = 8–38 mm Hg). Crude and adjusted logistic regression models identified several risk factors for hypotony and low IOP, which are summarized in Tables 1 and 2 . All patients with hypotony were over age 14, and the majority (57.1%, n = 8) were over age 18. Sex was not significantly associated with hypotony at presentation. Male sex was a risk factor for presenting with low IOP in univariate analysis (odds ratio [OR], 3.4; 95% CI, 1.3–8.8; P = .01) but did not achieve conventional statistical significance in the multivariate analysis.

In the univariate analyses, patients with ≥10 years duration of arthritis prior to presentation were significantly more likely to present with hypotony (OR, 16.2; 95% CI, 2.1–126.5; P = .008). Patients who presented to our clinic 4 or more years after the diagnosis of uveitis were 13-fold more likely to present with hypotony (95% CI, 1.7–101.4; P = .01). In over one-third (35.7%, n = 5) of hypotonous eyes, uveitis was first diagnosed at 3 years of age or younger, as compared with 11.5% (n = 21) of patients with nonhypotonous eyes (OR, 5.1; 95% CI, 1.5–17.7; P = .01). The median duration of uveitis was longer in hypotonous eyes than in eyes with IOP ≥5 mm Hg (17.0 years vs 3.8 years; P = .002). The vast majority of eyes with hypotony (92.9%, 13/14 eyes) had uveitis for longer than 5 years prior to presentation, whereas 44% of eyes with IOP ≥5 mm Hg (81/182) had uveitis longer than 5 years (OR, 7.2; 95% CI, 0.9–57.0; P = .06). Furthermore, eyes with evidence of increased disease severity including other structural ocular complications, such as posterior synechiae, were more likely to present with hypotony.

The majority of eyes with hypotony at presentation (57.1%, n = 8) had inflammation in the vitreous or posterior pole. These eyes were 17 times more likely to have hypotony (aOR, 16.9; 95% CI, 1.2–238; P = .04) when compared with eyes with isolated anterior uveitis. Eyes with panuveitis (35.7%, n = 5) were 13 times more likely to present with hypotony (OR, 13.3; 95% CI, 3.5–51.3, P < .001), and eyes with intermediate uveitis (21.4%, n = 3) were 6.7 times more likely to present with hypotony (OR, 6.7; 95% CI, 1.5–30.0; P = .01) compared with eyes with anterior uveitis. Eyes with active disease as defined by anterior chamber (AC) flare ≥1+ were more likely to present with hypotony (OR, 3.8; 95% CI, 1.0–14.0; P = .04) or low IOP (OR, 2.9; 95% CI, 1.0–8.5; P = .04); however, this risk factor was not statistically significant in the multivariate model.

Hypotony was associated with poor vision at presentation. The majority of hypotonous eyes (85.7%, n = 12) were legally blind (aOR, 7.6; 95% CI, 0.9–65.3; P = .06), and the rest (14.3%, n = 2) had visual acuity impairment (≤20/50 but >20/200). No eyes with hypotony at presentation had visual acuity of 20/40 or better, whereas 77.5% (n = 141) of nonhypotonous eyes had visual acuity of 20/40 or better at presentation. Four out of 14 hypotonous eyes at presentation had no follow-up visit. Over a median follow-up period of 11.5 years, 5 out of 10 hypotonous eyes at presentation showed no change in their visual acuity at the end of the follow-up period. Four eyes showed worsening of visual acuity (including 3 eyes with no light perception [NLP]), and only 1 eye showed slight improvement in vision from light perception (LP) to count finger (CF).

Eyes with a prior history of at least 1 intraocular surgery were statistically significantly more likely to present with hypotony (aOR, 76.3; 95% CI, 1.7–3406, P = .02). Thirteen of 14 hypotonous eyes (92.8%) had undergone cataract surgery prior to presentation, whereas 33 out of 182 eyes (18.3%) without hypotony had undergone cataract surgery at presentation. Subanalysis revealed that 82% of aphakic eyes at presentation had hypotony, vs only 9% of pseudophakic eyes at presentation (χ ² , P < .0001). Three hypotonous eyes had history of prior glaucoma surgery (2 eyes had trabeculectomy and 1 eye had peripheral laser iridotomy), and there was no significant association with hypotony (OR, 1.9; 95% CI, 0.5–7.3; P = .36).

Use of oral corticosteroid at presentation was a strong risk factor for hypotony (aOR, 46.6; 95% CI, 0.9–2297; P = .05) and low IOP (aOR, 14.2; 95% CI, 1.4–145.6; P = .02). Eyes with history of periocular corticosteroid injections were more likely to present with hypotony (aOR 30.7; 95% CI 1.4–669; P = .03) or low IOP (aOR, 20.5; 95% CI, 2.8–147; P = .003). Use of topical glaucoma drops, topical corticosteroids, mydriatic drops, glaucoma drops, or immunosuppressive drugs were not associated with hypotony or low IOP at presentation.

Incidence of Ocular Complications Among Eyes With Juvenile Idiopathic Arthritis–Associated Uveitis and Hypotony/Low Intraocular Pressure

Seventy-eight percent of patients were seen in follow-up, and the median follow-up period of these patients was 5.3 years (range, 2 weeks to 29.7 years). During follow-up, 26 of 137 developed hypotony, with a rate of 0.04 per eye-year (95% CI, 0.02/EY–0.05/EY, Figure 1 ), and 38 of 132 eyes developed low IOP (IOP <8 mm Hg) at the rate of 0.06 (95% CI, 0.04/EY–0.08/EY) ( Table 3 ). Although 4 out of 5 eyes with low IOP at presentation developed hypotony for at least 1 visit during follow-up at a rate of 0.48/EY (95% CI, 0.13/EY–1.23/EY), only 1 eye had sustained hypotony. During the follow-up period, some eyes improved in terms of IOP measurements, but the increases in IOP were typically 1–2 mm Hg. Although a small number of eyes had increases in IOP enough to move from the “hypotony” group to the “low IOP” group, no eyes improved enough to achieve sustained IOP ≥8 mm Hg (eg, the “normal IOP” group).

Kaplan-Meier estimate of development of hypotony (intraocular pressure <5) during follow-up in eyes with juvenile idiopathic arthritis–associated uveitis that were event-free at presentation.

Of the 26 eyes with newly diagnosed hypotony during follow-up, 12 had a history of recent glaucoma surgery. The median time between glaucoma surgery and development of new hypotony was 0.17 years (range: 1 week to 6.9 years). Among eyes with recent glaucoma surgery during follow-up, 9 eyes had recent tube shunt surgery, 2 eyes had recent trabeculectomy, and 1 eye had history of surgical peripheral iridotomy.

The majority of hypotonous eyes had visual impairment or legal blindness at the time of presentation. Among eyes with low IOP at presentation, the incidence rate of visual impairment (worse than 20/50 but better than 20/200) was 0.21/EY (95% CI, 0.01/EY–1.19/EY), vs 0.06/EY (95% CI, 0.04/EY–0.08/EY) in eyes with IOP ≥8 mm Hg at presentation (incidence rate ratio, 3.7; 95% CI, 0.1–22.3, P = .13). The incidence of legal blindness (20/200 or worse) was 0.12/EY in the eyes with low IOP (95% CI, 0.00/EY–0.67/EY) and 0.04/EY (95% CI, 0.02/EY–0.06/EY) in the eyes with IOP ≥8 mm Hg (incidence rate ratio, 3.1; 95% CI, 0.1–19.3, P = .16) ( Figure 2 ).

Kaplan-Meier (KM) estimate of development of legal blindness (visual acuity 20/200 or worse) during follow-up in eyes that were hypotony-free at presentation. The dashed line represents the KM estimate for eyes that stayed hypotony-free during follow-up, and the constant line refers to eyes with new hypotony during follow-up.

Risk Factors for Development of Hypotony During Follow-up

Univariate Cox regression analysis demonstrated that eyes with panuveitis (HR, 9.7; 95% CI, 3.2–29.1, P < .001), prior intraocular surgery (HR, 2.4; 95% CI, 1.1–5.5, P = .03), any structural ocular complications (defined as posterior synechiae, band keratopathy, cataract, glaucoma, optic disc edema, epiretinal membrane, or choroidal neovascularization; HR, 77.9; 95% CI, 1.9–33.6, P = .005), AC cell ≥3+ (HR, 2.5; 95% CI, 1.0–6.7, P = .04), AC flare ≥1+ (HR, 3.8; 95% CI, 1.6–9.0, P = .003), visual impairment (HR, 7.4; 95% CI, 2.9–18.9, P = .04), legal blindness (HR, 2.9; 95% CI, 1.0–7.9, P = .04), and treatment with ≤3 corticosteroid drops per day (HR, 3.0; 95% CI, 1.2–7.9, P = .02) at presentation were more likely to develop hypotony during follow-up. Patients who were receiving immunosuppressive therapy at presentation were statistically significantly less likely to develop hypotony during follow-up (HR, 0.1; 95% CI, 0.02–1.0, P = .05) ( Table 4 , Figure 3 ). After adjustment for statistically significant risk factors from the crude analysis, panuveitis remained associated with hypotony (aHR, 43.14; 95% CI, 3.27–569; P = .004), as did oral corticosteroid treatment (aHR, 28.95; 95% CI, 3.14–267.37, P = .003), presenting with ≥3+ AC cell or flare (aHR, 25.6; 95% CI, 4.53–144.93, P < .001), treating with lower dose of corticosteroid drops (aHR, 7.32; 95% CI, 1.34–39.9, P = .02), presence of posterior synechiae (aHR, 5.89; 95% CI, 1.28–26.91, P = .02), and visual impairment (aHR, 4.23; 95% CI, 1.01–17.69, P = .05) at presentation ( Table 5 ). In contrast, treatment with immunosuppressive drug therapy was associated with lower rates of hypotony (aHR, 0.02; 95% CI, 0.00–0.10, P = .002). Use of time-updated analyses for AC cell or flare and treatment with topical or oral corticosteroids or immunosuppressive drug therapy did not alter the results observed in the multivariable analysis (data not shown).

Table 4

Factors Influencing the Risk of Hypotony (<5 mm Hg) and Low Intraocular Pressure (IOP <8 mm Hg) in Patients With Juvenile Idiopathic Arthritis–Associated Uveitis: Results of Univariate Cox Proportional-Hazards Regressions

Variable	Hypotony (<5 mm Hg) (n = 137, Events = 26)		Low IOP (<8 mm Hg) (n = 132, Events = 38)
	HR (95% CI)	P Value	HR (95% CI)	P Value
Age at presentation (y)
<6	Reference		Reference
6–12	2.9 (0.8–11.1)	.11	2.7 (0.9–7.7)	.07
13–18	1.3 (0.2–7.7)	.79	1.9 (0.5–6.4)	.32
>18	3.5 (01.0–12.4)	.05*	2.9 (1.0–8.1)	.04*
Age at the time of uveitis diagnosis
<4 y	Reference		Reference
4–9 y	1.8 (0.5–6.1)	.36	1.8 (0.6–5.3)	.30
> 9 y	1.2 (0.3–4.6)	.79	2.5 (0.8–7.5)	.11
Sex
Female	Reference		Reference
Male	2.5 (1.1–5.6)	.03*	2.2 (1.1–4.5)	.03
Race
White	Reference		Reference
Black	3.1 (1.2–7.9)	.02*	2.1 (0.8–5.5)	.13
Other	0.7 (0.1–5.0)	.69	3.3 (1.1–9.7)	.03
Duration of uveitis prior to presentation (per year)	1.04 (1.0–1.1)	.006*	1.02 (0.99–1.05)	.05
Duration of uveitis at presentation
<6 months	Reference		Reference
6 months to 2 years	1.0 (0.3–3.3)	.96	1.0 (0.4–2.8)	.99
>2 years	1.4 (0.6–3.5)	.43	1.3 (0.6–2.9)	.44
Type of uveitis
Anterior	Reference		Reference
Intermediate or Ant+Int	0.8 (0.2–3.5)	.77	1.4 (0.5–4.0)	.50
Panuveitis	9.7 (3.2–29.1)	<.001*	7.5 (2.6–21.7)	<.001
Ocular surgery history
Any intraocular surgery	2.4 (1.1–5.5)	.03*	2.7 (1.4–5.5)	.005
Prior vitrectomy	4.9 (1.4–16.6)	.01*	1.9 (0.5–8.3)	.35
Prior cataract surgery	2.9 (1.2–6.6)	.01*	2.1 (0.9–4.6)	.07
Prior glaucoma surgery a	2.6 (0.9–7.5)	.09	4.5 (1.8–11.3)	.001
Signs of inflammatory activity
Anterior chamber cells
Quiet	Reference		Reference
0.5+	2.1 (0.7–6.2)	.17	1.6 (0.6–4.3)	.37
1+	0.9 (0.2–3.2)	.86	0.6 (0.2–2.0)	.37
2+	1.7 (0.5–6.2)	.42	3.0 (1.2–7.9)	.02
3+ or worse	3.0 (1.0–8.9)	.04*	3.0 (1.2–7.6)	.02
Anterior chamber flare
Quiet	Reference		Reference
1+	2.3 (0.8–6.8)	.14	2.1 (0.9–4.7)	.08
2+	4.7 (1.8–12.2)	.001*	3.3 (1.5–7.3)	.004
3+ or worse	86.5 (13–576)	<.001*	215.7 (18.7–2485)	<.001
Structural complications at presentation
Any structural complications	7.9 (1.9–33.6)	.005*	2.8 (1.3–6.2)	.01
Posterior synechiae	2.8 (1.3–6.0)	.01*	2.1 (1.1–4.2)	.03
Epiretinal membrane	6.2 (1.8–21.1)	.003*	4.7 (1.4–15.5)	.01
Treatment at presentation
Topical corticosteroid drops
None	Reference		Reference
1–3 drops/d	3.0 (1.2–7.9)	.02*	4.0 (1.7–9.3)	.001
>3 drops/d	1.0 (0.4–2.4)	.96	1.0 (0.5–2.1)	.98
Topical mydriatic drops	1.8 (0.7–4.2)	.20	1.5 (0.7–3.4)	.28
Topical IOP-lowering drops	2.3 (0.9–6.3)	.09	1.8 (0.8–4.3)	.17
Oral corticosteroid	2.4 (0.8–6.8)	.12	3.0 (1.1–7.8)	.02
Immunosuppressive agents	0.1 (0.02–1.0)	.05*	0.7 (0.3–1.6)	.42
Prior priocular corticosteroid injection(s)	3.3 (1.3–8.3)	.01*	2.3 (1.0–5.0)	.04
Visual acuity at presentation
20/40 or better	Reference		Reference
20/50 to 20/160	7.4 (2.9–18.9)	<.001*	3.5 (1.4–8.7)	.006
20/200 or worse	2.9 (1.0–7.9)	.04*	3.1 (1.3–7.4)	.01

Only gold members can continue reading. Log In or Register to continue

Share this:

• Click to share on Twitter (Opens in new window)
• Click to share on Facebook (Opens in new window)

Related

Related posts:

1. Analysis of Intraocular Lens Biofilms and Fluids After Long-Term Uncomplicated Cataract Surgery
2. Extent of Internal Limiting Membrane Peeling and its Impact on Macular Hole Surgery Outcomes: A Randomized Trial
3. Penetrating Keratoplasty for Keratoconus With and Without Resolved Corneal Hydrops: Long-term Results
4. Pars Plana Vitrectomy Combined With Either Secondary Scleral Fixated or Anterior Chamber Intraocular Lens Implantation

Stay updated, free articles. Join our Telegram channel

Join