Purpose
To determine the incidence of and predictive factors for cataract in intermediate uveitis.
Design
Retrospective cohort study.
Methods
Patients were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study, in which medical records were reviewed to determine demographic and clinical data of every eye/patient at every visit at 5 participating US tertiary care uveitis centers. The primary outcome was development of vision-compromising cataract as defined by a decrease in visual acuity to 20/40 or less, or requiring cataract surgery. Survival analysis assessed visually defined cataract to avoid bias due to timing of surgery vis-à-vis inflammatory status.
Results
Among 2,190 eyes of 1,302 patients with intermediate uveitis, the cumulative incidence of cataract formation was 7.6% by 1 year (95% confidence interval [CI] = 6.2%-9.1%), increasing to 36.6% by 10 years (95% CI = 31.2%-41.6%). Increased cataract risk was observed in eyes with concurrent anterior uveitis causing posterior synechiae (hazard ratio = 2.68, 95% CI = 2.00-3.59, P < .001), and in eyes with epiretinal membrane formation (hazard ratio = 1.54, 95% CI = 1.15-2.07, P = .004). Higher dose corticosteroid therapy was associated with significantly higher incidence of cataract, especially time-updated use of topical corticosteroids ≥2 times/d or ≥4 periocular corticosteroid injections. Low-dose corticosteroid medications (oral prednisone 7.5 mg daily or less, or topical corticosteroid drops <2 times/d) were not associated with increased cataract risk.
Conclusions
Our study found that the incidence of clinically important cataract in intermediate uveitis is moderate. The risk is higher with markers of severity and with higher doses of corticosteroid medications, the latter being potentially modifiable.
U veitis represents a heterogeneous group of inflammatory conditions affecting the eye and is estimated to be responsible for as much as 10%-15% of visual loss in the adult population worldwide. Cataracts are among the complications of uveitis that can impair vision. Uveitic cataracts may require surgery to improve visual function, prevent further inflammation, or allow improved clinical examination for treatment and monitoring. Studies have shown that controlling intraocular inflammation reduces the incidence of cataracts. The primary treatments used in managing uveitis also are potentially cataractogenic. , Therefore, prompt treatment of intraocular inflammation while minimizing corticosteroid exposure is of the utmost importance for preventing complications of uveitis and vision loss.
Within the broader category of uveitis, patients can be categorized according to the primary site of inflammation within the eye; intermediate uveitis refers to inflammation that primarily affects the vitreous. Intermediate uveitis constitutes 2%-31% of all uveitis, and cataract has been reported to be one of the most common complications in this disease. Patients with intermediate uveitis often require systemic immunomodulatory therapy (IMT) and close monitoring given the potential for exacerbations, but with proper and timely treatment good visual acuity can be maintained. Indeed, after 7 years of follow-up in the Multicenter Uveitis Steroid Treatment (MUST) Trial, patients treated with systemic anti-inflammatory therapy, including those with intermediate uveitis, maintained their baseline visual acuity on average.
Uveitic cataracts pose a particular challenge for the surgeon as eyes with prior inflammation are prone to intraocular scarring, poor pupillary dilation, abnormally fragile iris vasculature, and repeat inflammation in the perioperative period. , These concerns apply in the subset of patients with intermediate uveitis as well. However, the situation regarding cataract incidence and its treatment may differ from anterior uveitis because the primary site of inflammation is behind rather than around the lens. Understanding the risks of cataract formation and need for cataract surgery in intermediate uveitis can help guide treatment and inform patient counseling. In this study, we analyze the incidence of clinically significant cataract in a large cohort of eyes of patients with intermediate uveitis.
METHODS
Study Population
Cases of intermediate uveitis were identified from the Systemic Immunosuppressive Therapy for Eye Disease (SITE) Cohort Study, a large retrospective study of patients with noninfectious inflammatory eye disease examined at US tertiary subspecialty centers, which has been previously described. , The study subsequently has been extended to include all eligible patients at the 5 centers from inception of the subspecialty uveitis practice at each through December 31, 2010. Those diagnosed with intermediate uveitis at the participating 5 core centers were included in this study. Intermediate uveitis had been defined as inflammation primarily localized to the vitreous, following the definition eventually agreed upon by the Standardization of Uveitis Nomenclature (SUN) Working Group. Patients with combined anterior and intermediate uveitis were included; special note was made of eyes with anterior uveitis or signs thereof, and analyses were adjusted for this factor. The Institutional Review Boards of the University of Pennsylvania, Oregon Health & Science University, Johns Hopkins School of Medicine, Massachusetts Eye and Ear, and the National Eye Institute approved the study, including waiver of informed consent for this retrospective cohort study, which involved no contact with human subjects. The study was conducted adhering to the tenets of the Declaration of Helsinki, and was compliant with all relevant laws.
Data Collection
All data collected had been entered into a computer-based standardized data form developed specifically for the SITE study. This system included built-in quality control measures and allowed for correction of data in real time. Data evaluated for this paper (see Tables 1 and 2 ) included patients’ demographic characteristics, objective inflammatory findings, duration of uveitis, and previous treatments pursued, including medication use and prior surgeries. Whether or not patients were taking several different common systemic medications, including aspirin, statins, angiotensin-converting enzyme inhibitors, and nonsteroidal anti-inflammatory drugs, was also noted to assess the hypotheses that each of these might modify the risk of cataract. The presence or absence of cataract in the fellow eye was also noted.
| Cox Model of Cataract by Visual Acuity | ||||||||
|---|---|---|---|---|---|---|---|---|
| Cataract | Crude | Adjusted a | ||||||
| Total | No | Yes | Hazard Ratio (95% CI) | P | Hazard Ratio (95% CI) | P | ||
| Age at presentation | <40 | 1,344 (61%) | 1,190 (89%) | 154 (11%) | Ref | .30 | Ref | .19 |
| 40-60 | 657 (30%) | 572 (87%) | 85 (13%) | 1.14 (0.84, 1.55) | 1.04 (0.76, 1.42) | |||
| >60 | 189 (9%) | 170 (90%) | 19 (10%) | 1.52 (0.86, 2.70) | 1.73 (0.96, 3.12) | |||
| Sex | Male | 785 (36%) | 696 (89%) | 89 (11%) | Ref | .90 | Ref | .89 |
| Female | 1,405 (64%) | 1,236 (88%) | 169 (12%) | 1.02 (0.76, 1.37) | 0.98 (0.73, 1.31) | |||
| Race category | White | 1,569 (72%) | 1,388 (88%) | 181 (12%) | Ref | .51 | Ref | .45 |
| Black | 219 (10%) | 186 (85%) | 33 (15%) | 1.26 (0.85, 1.86) | 1.30 (0.84, 1.99) | |||
| Hispanic | 83 (4%) | 75 (90%) | 8 (10%) | 0.73 (0.35, 1.53) | 0.81 (0.38, 1.75) | |||
| Other | 319 (15%) | 283 (89%) | 36 (11%) | 1.04 (0.70, 1.55) | 1.22 (0.83, 1.81) | |||
| Smoking | Never | 1,311 (60%) | 1,168 (89%) | 143 (11%) | Ref | .24 | Ref | .53 |
| Past | 203 (9%) | 175 (86%) | 28 (14%) | 1.23 (0.75, 2.00) | 1.06 (0.64, 1.75) | |||
| Current | 484 (22%) | 417 (86%) | 67 (14%) | 1.43 (1.01, 2.02) | 1.27 (0.90, 1.80) | |||
| Unknown | 192 (9%) | 172 (90%) | 20 (10%) | 1.11 (0.65, 1.87) | 0.91 (0.48, 1.72) | |||
a Adjusted for PPV, posterior synechia, epiretinal membrane, any IMTs, cumulative periocular corticosteroid injections, topical corticosteroids, and oral corticosteroids.
| Cox Model of Cataract by Visual Acuity | ||||||||
|---|---|---|---|---|---|---|---|---|
| Cataract | Crude | Adjusted a | ||||||
| Total | No | Yes | Hazard Ratio (95% CI) | P | Hazard Ratio (95% CI) | P | ||
| Anterior/intermediate uveitis at baseline | No | 1,564 (72%) | 1,411 (90%) | 153 (10%) | Ref | <.001 | Ref | .75 |
| Yes | 622 (28%) | 517 (83%) | 105 (17%) | 1.76 (1.32, 2.34) | 1.05 (0.76, 1.46) | |||
| Bilateral uveitis | No | 227 (10%) | 197 (87%) | 30 (13%) | Ref | .15 | Ref | .10 |
| Yes | 1,963 (90%) | 1,735 (88%) | 228 (12%) | 0.75 (0.50, 1.11) | 0.70 (0.46, 1.07) | |||
| Duration of uveitis before presentation | <6 mo | 816 (37%) | 747 (92%) | 69 (8%) | Ref | .06 | Ref | .19 |
| 6 mo to <2 y | 507 (23%) | 443 (87%) | 64 (13%) | 1.35 (0.91, 2.01) | 1.32 (0.89, 1.95) | |||
| 2+ y | 865 (40%) | 741 (86%) | 124 (14%) | 1.53 (1.08, 2.17) | 1.43 (0.97, 2.11) | |||
| Cataract in other eye b | No | 2,008 (92%) | 1,761 (88%) | 247 (12%) | Ref | .59 | Ref | .48 |
| Yes | 182 (8%) | 171 (94%) | 11 (6%) | 1.11 (0.76, 1.62) | 0.86 (0.56, 1.31) | |||
| Inflammatory activity b | Inactive | 392 (18%) | 356 (91%) | 36 (9%) | Ref | .16 | Ref | .12 |
| Slightly active | 238 (11%) | 221 (93%) | 17 (7%) | 1.41 (0.97, 2.06) | 1.24 (0.84, 1.83) | |||
| Active | 1,554 (71%) | 1,349 (87%) | 205 (13%) | 1.00 (0.72, 1.38) | 0.82 (0.59, 1.14) | |||
| Epiretinal membrane b | No | 2,003 (92%) | 1,775 (89%) | 228 (11%) | Ref | <.001 | Ref | .004 |
| Yes | 180 (8%) | 151 (84%) | 29 (16%) | 1.91 (1.45, 2.51) | 1.54 (1.15, 2.07) | |||
| Posterior synechia b | No | 1,925 (88%) | 1,725 (90%) | 200 (10%) | Ref | <.001 | Ref | <.001 |
| Yes | 258 (12%) | 200 (78%) | 58 (22%) | 3.01 (2.27, 3.99) | 2.68 (2.00, 3.59) | |||
| Pars plana vitrectomy (not for retinal detachment) | No | 2,128 (97%) | 1,880 (88%) | 248 (12%) | Ref | <.001 | Ref | .004 |
| Yes | 62 (3%) | 52 (84%) | 10 (16%) | 2.26 (1.46, 3.51) | 1.92 (1.24, 2.98) | |||
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