Adverse Events after Intravitreal Triamcinolone in Patients with and without Uveitis

doi:10.1016/j.ophtha.2007.05.037

Ophthalmology

Volume 114, Issue 10, October 2007, Pages 1912-1918

Presented as a poster at: American Academy of Ophthalmology meeting, October 2005, Chicago, Illinois.

https://doi.org/10.1016/j.ophtha.2007.05.037 Get rights and content

Purpose

To evaluate the rates of adverse ocular events after intravitreal triamcinolone acetonide (IVTA) injection in patients with and without uveitis.

Design

Retrospective observational case series.

Participants

Two hundred twenty-two eyes of 173 patients were included in the study: 45 eyes of 31 patients with macular edema (ME) due to uveitis and 177 eyes of 142 patients with ME secondary to other etiologies.

Methods

Retrospective review of patients who received IVTA at the Cole Eye Institute for ME attributable to various causes between the years 2001 and 2005. Data review of clinical records included patient demographics, etiology of ME, and adverse outcomes after injection. Rates of adverse outcomes in patients with and without uveitis were compared.

Main Outcome Measures

Intraocular pressure (IOP) elevation and posterior subcapsular cataract (PSC) progression.

Results

Uveitis patients were significantly younger, more likely to be female, and more likely to have had prior posterior sub–Tenon’s capsule steroid injection and/or glaucoma therapy than their nonuveitis counterparts. In a multivariate analysis adjusting for the differences in these factors, the presence of uveitis was the strongest risk factor for an adverse IOP event (odds ratio, 2.5; 95% confidence interval [CI], 1.0–6.1; P = 0.05). The odds of having a documented increase in PSC after IVTA injection were 5.6 times greater in uveitis eyes (P = 0.007; 95% CI, 1.6–19.6).

Conclusions

Intraocular pressure elevation and PSC progression occurred with greater frequency in uveitis patients receiving IVTA. Patients with uveitis treated with IVTA should be counseled about these risks and monitored closely.

Section snippets

Materials and Methods

A retrospective chart review was performed of patients who received IVTA (Kenalog 40, Bristol-Myers Squibb, Princeton, NJ) for ME at the Cole Eye Institute between August 2001 and July 2005. After approval was obtained from the Cleveland Clinic Foundation Institutional Review Board to conduct the chart review, the computerized database of the Cole Eye Institute was used to identify all patients who received IVTA for treatment of ME. The search criteria identified patients based on the Current

Results

The study included 222 eyes of 173 patients: 45 eyes of 31 patients with ME due to uveitis and 177 eyes of 142 patients with ME secondary to other etiologies. Diabetes and retinal vein occlusion were the 2 most common causes of nonuveitic ME (Table 1). Nineteen eyes (42%) with ME secondary to uveitis had a known associated systemic condition (Table 2).

Comparison of clinical characteristics between the 2 groups demonstrated significant differences with respect to several baseline factors (Table 3

Discussion

Intravitreal triamcinolone has become a widely used treatment for ME. It has been shown to result in at least temporary visual improvement in patients with ME secondary to diabetes mellitus and retinal vein occlusions.28, 29, 30, 31 The increased use of this drug in treating numerous conditions associated with ME has prompted several studies evaluating the efficacy of treatment as well as potential adverse effects—namely, IOP elevation and cataract progression.

Several studies have reported the

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Cited by (43)

Risk of Cataract in Intermediate Uveitis
2021, American Journal of Ophthalmology
Citation Excerpt :
If PPV is pursued to treat intermediate uveitis, the effects of vitrectomy on cataract formation should be considered in evaluating the potential benefit of inflammation remission. Also in keeping with prior reports,3,7,25-28 this study found an increased risk of cataract formation with increased corticosteroid use. The risk of cataract with systemic, topical ophthalmic, or periocular corticosteroids is well established, but here we characterize the risk associated with different levels of corticosteroid therapy specifically in the intermediate uveitis context.
To determine the incidence of and predictive factors for cataract in intermediate uveitis.
Retrospective cohort study.
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.
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.
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.
Ocular hypertension following 40 mg sub-Tenon triamcinolone versus 0.7 mg dexamethasone implant versus 2 mg intravitreal triamcinolone
2020, Canadian Journal of Ophthalmology
Citation Excerpt :
The only significant difference in rate of OHT in the POINT trial was found when comparing STT and DEX. Previous studies have shown that a history of uveitis is a risk factor for developing OHT when receiving intravitreal steroids.30,31 Given that only eyes with uveitis were included in the POINT trial and the higher 4 mg dose IVT was used,24,26,27 comparing rates of OHT to our study is challenging.
To compare rates of ocular hypertension (OHT) in eyes receiving 40 mg sub-Tenon triamcinolone (STT), 0.7 mg dexamethasone implant (DEX), and 2 mg intravitreal triamcinolone (IVT).
This study is a single-centre, retrospective case series. All patients receiving STT and DEX between 4/1/2014 and 3/1/2017 and IVT between 3/1/2012 and 3/1/2017 with a minimum of 3 months’ follow-up were included. OHT was defined as an intraocular pressure (IOP) >24 mm Hg. Patients receiving any other form of topical, oral, or intravitreal steroid were excluded.
113 eyes from 104 patients in the STT group, 122 eyes from 109 patients in the DEX group, and 109 eyes from 103 patients in the IVT group were included. The mean number of injections for each eye was 1.7 in the STT group, 2.6 for the DEX group, and 2.8 for the IVT group (p < 0.001). Twenty eyes (17.7%) developed OHT in the STT group, 19 eyes (15.6%) developed OHT in the DEX group, and 14 eyes (12.8%) developed OHT in the IVT group (p = 0.60). IOP was controlled in all eyes with observation, topical IOP-lowering medication, or surgical intervention. The rate of incisional glaucoma surgery was 1.7% in the STT group, 1.6% in the DEX group, and 0% in the IVT group (p = 0.55).
The rate of OHT was similar across treatment groups. The proportion of OHT in patients with a history of glaucoma was no different from that in patients without a history of glaucoma. All cases were successfully managed with observation, medical treatment, or incisional surgery.
Comparer le taux d'hypertension oculaire (HTO) dans des yeux soumis à l'un des traitements suivants : 40 mg de triamcinolone administrés sous la capsule de Tenon (TSCT); implant de dexaméthasone dosé à 0,7 mg (DEX) ou injection intravitréenne de 2 mg de triamcinolone (IIVT).
Cette étude rétrospective d'une série de cas a été réalisée dans un seul centre. Ont été inclus tous les patients qui ont reçu la TSCT ou un DEX du 4/1/2014 au 3/1/2017 et une IIVT du 3/1/2012 au 3/1/2017 et qui ont fait l'objet d'un suivi minimum de 3 mois. L'HTO se définissait comme une pression intraoculaire (PIO) > 24 mm Hg. Les patients qui recevaient toute autre forme de stéroïdes (topiques, oraux ou intravitréens) ont été exclus.
Ainsi, 113 yeux de 104 patients dans le groupe TSCT, 122 yeux de 109 patients dans le groupe DEX et 109 yeux de 103 patients dans le groupe IIVT ont été inclus. Le nombre moyen d'injections dans chaque œil était de 1,7 dans le groupe TSCT, de 2,6 dans le groupe DEX et de 2,8 dans le groupe IIVT (p < 0,001). Il est apparu une HTO dans 20 yeux (17,7 %) du groupe TSCT, 19 yeux (15,6 %) du groupe DEX et 14 yeux (12,8 %) du groupe IIVT (p = 0,60). Dans tous les yeux, la PIO a été prise en charge de l'une des 3 façons suivantes : observation, médicament topique pour abaisser la PIO ou intervention chirurgicale. Le taux de chirurgie incisionnelle du glaucome se chiffrait à 1,7 % dans le groupe TSCT, à 1,6 % dans le groupe DEX et à 0 % dans le groupe IIVT (p = 0,55).
Le taux d'HTO était semblable dans tous les groupes de traitement. La proportion d'HTO ne différait pas, que les patients aient ou non des antécédents de glaucome. L'observation, le traitement médicamenteux ou la chirurgie incisionnelle ont permis la prise en charge réussie de tous les cas d'HTO.
Cataract in the Adult Eye Preferred Practice Pattern®
2017, Ophthalmology
Intraocular Pressure Monitoring Post Intravitreal Steroids: A Systematic Review
2013, Survey of Ophthalmology
Citation Excerpt :
A family history of glaucoma may also be a risk factor for OHT following IVT steroid.2 Among posterior segment diseases that required IVT steroid, only uveitis has been reported as a risk factor for OHT after IVT TA injection.63,104 Our analysis of OHT following IVT TA injection found the highest prevalence of OHT in uveitis patients (42.7%; 95% CI, 28.4–58.3) followed by macular degeneration (38.5%; 95% CI, 33.8–43.4), retinal vein occlusion (35.9%; 95% CI, 30.7–41.5), DME (32.3%; 95% CI, 27.5–37.5), and choroidal neovascular membrane (30.4%; 95% CI, 24.3–37.4).
The use of intravitreal (IVT) corticosteroids for treatment of posterior segment diseases has increased significantly over the last decade. A commonly recognized complication of IVT steroids is secondary ocular hypertension (OHT) that can occur immediately secondary to direct intraocular volume increase or weeks to months later as a result of increased outflow resistance. We performed a meta-analysis and found 32% (95% confidence interval, 28.2–36.3) of individuals developed OHT following 4 mg IVT triamcinolone, 66% (50.2–78.8) and 79% (72.2–84.5) following 0.59 and 2.1 mg fluocinolone implant, respectively, and 11% (6.4–17.9) and 15% (9.2–24.3) following 0.35 and 0.7 mg dexamethasone implant, respectively. Risk factors included pre-existing glaucoma, higher baseline intraocular pressure (IOP), younger age, OHT following previous injection, uveitis, higher steroid dosage, and fluocinolone implant. Most cases of OHT can be controlled medically; up to 45% following fluocinolone implant require surgery, however. We suggest a protocol to monitor IOP after IVT steroid injection/implantation that includes checking IOP within 30 minutes after injection, followed by 1 week after IVT triamcinolone and 2 weeks after implant insertion, then every 2 weeks for the first month and monthly for up to 6 months after IVT triamcinolone and dexamethasone implantation and 9 months after fluocinolone implantation.
Suppression of phagocytic cells in retinal disorders using amphiphilic poly(γ-glutamic acid) nanoparticles containing dexamethasone
2011, Journal of Controlled Release
Citation Excerpt :
Subtenon or intravitreal administration of triamcinolone acetate (IVTA), a type of steroid, has been effective in the treatment of several retinal disorders, including uveitis, diabetic macular edema, laser injury, and branch or central retinal vein occlusion [31,32]. However, 30 to 40% of patients with IVTA experienced complications of steroid-induced glaucoma [33–35] and post-capsular cataract formation [36], and 59% of patients with preexisting glaucoma required additional glaucoma medications [33]. Furthermore, direct administration of steroids is toxic for retinal neurons [37].
To investigate the potential of nanoparticles (NPs) composed of poly(γ-glutamic acid) conjugated with l-phenylalanine (γ-PGA-Phe NPs) for the treatment of retinal diseases, γ-PGA-Phe NPs (200 nm) were tested with macrophages and microglia in vitro or by intravitreal administration into normal or pathological rat eyes. The anti-inflammatory effects of the NPs containing dexamethasone (DEX-NPs) were examined using qRT-PCR in vitro by counting activated microglia and Fluorogold-labeled retinal ganglion cells in the retinas under excitotoxicity or by counting TUNEL (+) photoreceptors in the detached retinas. The NPs were taken up efficiently by cultured macrophages or microglia. At day 7, 60–80% of the diffuse signal remained in the cytoplasm of these cells. In normal rat eyes, the NPs did not accumulate in the retinas and no inflammatory cells were recruited. Conversely, under pathological conditions, the NPs were localized in activated CD11b-positive cells in the retina. DEX-NPs suppressed the expression of TNFα and MCP-1 in cultured macrophages or microglia, the activation of microglia, the loss of retinal ganglion cells (RGCs) in excitotoxic retinas, and the number of TUNEL (+) photoreceptors in detached retinas. These data suggest that γ-PGA-Phe NPs can be a powerful tool for suppressing inflammatory cells in pathological conditions in the retina.
Effectiveness of interferon alpha in the treatment of uveitis macular edema refractory to corticosteroid and/or immunosuppressive treatment
2010, Journal Francais d'Ophtalmologie
La survenue d’un œdème maculaire est toujours une complication majeure dans le cadre d’uvéite intermédiaire et/ou postérieure. Certains de ces œdèmes sont réfractaires aux traitements par corticoïde et/ou immunosuppresseur. L’interféron (IFN), validé dans le traitement de la maladie de Behçet, possède des propriétés immunorégulatrices et antiprolifératives qui en font une molécule intéressante dans les œdèmes maculaires uvéititques réfractaires au traitement corticoïde avec ou sans immunosuppresseur. Des études récentes ont mises en évidence un déficit en IFN-α chez des patients uvéitiques.
Nous rapportons les cas consécutifs de six patients ayant présenté des œdèmes maculaires uvétiques, dont deux au cours d’une choriorétinopathie de Birdshot et quatre au cours d’uvéites d’origine idiopathique, réfractaires au traitement anti-inflammatoire et/ou immuno-suppresseur et traités par IFN-α. Une diminution moyenne de l’épaisseur des 1 000 μm centraux de 189,7 ± 67 μm et un gain moyen d’acuité visuelle de 0,35 ± 0,21 LogMAR étaient notés. Un seul cas de dépression avérée est survenu au cours du traitement.
Toutes les études cliniques montrent une efficacité remarquable de l’IFN-α sur l’œdème maculaire en moins d’un mois. Notre petite série retrouve une efficacité similaire, et ce malgé une attitude thérapeutique moins agressive que celle des études précédentes. On retrouve malgré tout les effets secondaires de l’IFN, au premier rang desquels le syndrome dépressif.
Dans notre série de six cas cliniques consécutifs d’œdème maculaire uvéitique réfractaire aux corticoïdes et/ou immunosuppresseur, l’IFN-α a montré un résultat anatomique et fonctionnel très intéressant. Les modalités exactes de mise en œuvre et de posologie restent à définir. Toutefois, il semble qu’une posologie plus faible et une durée de traitment plus courte que celle proposée dans la littérature puissent être aussi efficaces, tout en diminuant le taux de complications.
Macular edema is always a major complication in intermediate and/or posterior uveitis. Some of these macular edemas are refractory to steroid and/or immunosuppressive drugs. Interferon, a validated treatment for Behçet disease, has antiproliferative and immunoregulative properties that may be very valuable in uveitic edema refractory to steroid and/or immunosuppressive agents. Recent studies have brought out the value of interferon-alpha by demonstrating its low blood rate in affected patients.
We describe a series of six consecutive uveitic macular edema, secondary to two birdshot retinochoroidopathy, and four cases of idiopathic uveitis treated with interferon-alpha. Our small case series showed a 189.7 ± 67 μm decrease in mapping and an improvement in visual acuity of 0.35 ± 0.21 LogMAR.
Other publications have shown a remarkable efficacy on macular edema and visual acuity in less than 1 month of treatment. Our small case series found the same results as the other studies, despite a less aggressive therapeutic regimen. However, we also observed some well-known side effects, in particular depression.
In our series of six consecutive cases of uveitic macular edema refractory to steroid or immunosuppressive drugs, alpha-interferon provided highly advantageous anatomical and functional results. The treatment modality must be specified, but it seems that a shorter duration and lower posologies might be as effective and lead to a lower rate of complications than the regimen currently proposed in the literature.

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: Manuscript no. 2006-1012.

: The authors have no financial conflicts.

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Original articleAdverse Events after Intravitreal Triamcinolone in Patients with and without Uveitis

Purpose

Design

Participants

Methods

Main Outcome Measures

Results

Conclusions

Section snippets

Materials and Methods

Results

Discussion

Ophthalmology

Ophthalmology

Ophthalmology

Am J Ophthalmol

Am J Ophthalmol

Am J Ophthalmol

Am J Ophthalmol

Ophthalmology

Eur J Pharmacol

Ophthalmology

Ophthalmology

Am J Ophthalmol

Ophthalmology

Am J Ophthalmol

Am J Ophthalmol

Am J Ophthalmol

Ophthalmology

Can J Ophthalmol

Intravitreal injection of triamcinolone for diffuse diabetic macular edema

Arch Ophthalmol

Intravitreal triamcinolone injection for chronic diffuse diabetic macular oedema

Clin Experiment Ophthalmol

Intravitreal triamcinolone acetonide in refractory pseudophakic cystoid macular edema: functional and anatomic results

Eur J Ophthalmol

Intravitreal triamcinolone acetonide for the treatment of chronic pseudophakic cystoid macular oedema

Acta Ophthalmol Scand

Intravitreal triamcinolone for the management of macular edema due to nonischemic central retinal vein occlusion

Arch Ophthalmol

Intravitreal triamcinolone for the treatment of macular edema associated with central retinal vein occlusion

Arch Ophthalmol

Original article
Adverse Events after Intravitreal Triamcinolone in Patients with and without Uveitis