Dexamethasone & Treatment Of Non-Infectious Posterior Segment Uveitis

Dexamethasone & Treatment Of Non-Infectious Posterior Segment Uveitis

April 12, 2021

Uveitis of the posterior segment encompasses a variety of diagnostic descriptions, namely intermediate uveitis, posterior uveitis, and panuveitis. Uveitis affecting the posterior segment can be infectious, although most cases are noninfectious.

Corticosteroids and immunomodulatory drugs are the cornerstones for treatment of noninfectious uveitis in the posterior segment. Treatment of posterior uveitis generally necessitates the use of intraocular injections/implants or systemic therapies.

Local corticosteroids are used when inflammation, or residual inflammation in the case of a systemically treated patient, is limited to the eye. Subtenon triamcinolone injections are most commonly used in clinical practice.

As with all treatments, there are some limitations. Clinical experience has shown that a percentage of patients will develop high IOP and/or cataract as a result of these injections, and it is difficult to predict which patients will have that response.

As for systemic treatments, corticosteroids are the first-line drug in noninfectious inflammatory conditions, including posterior segment uveitis. When >10 mg/d corticosteroid treatment is needed to keep ocular inflammation controlled, immunomodulatory therapies (IMTs) are used.

In Europe, cyclosporine, mycophenolate, azathioprine, and methotrexate are the most common IMTs used for noninfectious posterior segment uveitis.

For patients whose uveitis is refractory to traditional immunosuppressants, infliximab and adalimumab are the anti-TNF-a biologics that are most often used.

There is evidence that patients with certain systemic etiologies are best treated early with the anti-TNF-a medications.

Adamantiades-Behçet disease is believed to respond well to infliximab, and pediatric posterior segment uveitis patients, including those whose condition is associated with juvenile idiopathic arthritis, do well on adalimumab.

Regarding other biologics, interferon and the interleukin-6 inhibitor tocilizumab are beginning to be used more. The results of a small retrospective cohort study has been published recently showing success when treating inflammatory macular edema refractory to the anti-TNF-a medications.

Interferon is used mostly in Germany and Turkey, mainly in Behçet disease and in cases with macular edema. An advantage of interferon is that when treatment is stopped, a high percentage of patients remain in remission.

LOUVRE 2 STUDY

FINDINGS IN LOUVRE 2, a French postmarketing, prospective, observational study, confirm the real-world efficacy of the dexamethasone 0.7 mg intravitreal implant (Ozurdex, Allergan) for treating relatively long-standing non-infectious posterior segment uveitis.

The findings also provide insight into the characteristics of patients ophthalmologists choose for treatment with the sustained-release corticosteroid implant. Noninfectious posterior segment uveitis [NIPU] is the least common form of uveitis, yet it is the most vision-threatening form.

In addition to its potential to cause sudden/ severe vision loss, it can be associated with painful symptoms. Because of its sequelae, NIPU can lead to a marked decrease in quality of life.

In this cohort of patients seen in routine clinical practice, consisting mostly of individuals previously treated for uveitis for an average of 5 years, the intravitreal dexamethasone implant maintained its functional and anatomic efficacy.

In addition, the tolerability of the steroid implant treatment was consistent with what has been reported in the literature. With its approval in July 2010, the dexamethasone intravitreal implant became the first specialized treatment for NIPU in Europe.

Thereafter, the prospective, multicenter, observational LOUVRE 2 study was implemented in France to evaluate the real-world efficacy, safety, and use of the implant in patients affected by NIPU. The study enrolled consecutively presenting patients with inflammation of the posterior ocular segment due to NIPU.

Twenty randomly selected injection centers participated in the study. Both treatment-naive and previously treated patients were eligible for enrollment. Patients who were treated with the dexamethasone implant on study entry could be retreated with the implant and/or alternative therapies during follow-up.

According to the protocol, outcomes would be analyzed using data from visits at months 2, 6, and 18 after patient enrollment. A batch recall of the implant at the end of 2018 led to early termination of the study, and only a few patients reached the month 18 visit.

Efficacy assessments included changes in best corrected visual acuity (BCVA) and central retinal thickness (CRT). Safety evaluations reviewed AE reports. Baseline data were available for 241 patients, including 97 who were treated with the dexamethasone implant at study entry.

The patients who were treated with dexamethasone had on average a 5-year history of NIPU, and 80% had received prior treatment.

Compared with the group of 144 patients that did not receive the implant, those treated who received the dexamethasone implant were 7.9 years older on average and had a thicker mean CRT (mean difference 91.2 µm).

In addition, the group treated with the dexamethasone implant included greater proportions of patients with cataract (20.0% difference), macular edema (26.2% difference), and inflammation-associated pathology (8.8% difference).

Half the patients treated with the dexamethasone implant at entry into LOUVRE 2 were not retreated at month 6, mainly because they had sufficient improvement of their disease state.

The proportion of dexamethasone-treated patients achieving a greater than or equal to 15-letter gain in BCVA from baseline was 25% at month 2 and 19.4% at month 6. Mean improvement from baseline BCVA was 6.2 letters at 2 months and 4.3 letters at 6 months.

Central retinal dryness was maintained at months 2 and 6 with mean decreases from baseline of 27.4 and 18.5 μm, respectively.

The observed functional gains are clinically relevant and were achieved despite prior treatment with the dexamethasone implant in 55.7% of the patients followed prospectively.

 

These findings substantiate the efficacy of the dexamethasone implant for improving visual function among patients with NIPU in seen the clinical setting. The most frequently reported AE occurring in patients treated with the dexamethasone implant was transient ocular hypertension, which occurred at a rate of 6.9%.

This finding is similar to the experience reported with the dexamethasone implant in prior prospective and retrospective studies.