Intermediate Uveitis Treatment & Management

Treatment considerations include the following:

• Treatment of intermediate uveitis is undertaken to prevent permanent structural damage to vital ocular tissue, and, as a consequence, the method outlined by Kaplan is outdated. ^[8]

• Whereas mild asymptomatic vitreous cell may not require immediate treatment, any evidence of CME, neovascularization of the peripheral retina, extensive vasculitis, or significant vitreous cell requires treatment.

• Treatment is no longer based on an arbitrary level of vision. As with most forms of uveitis, corticosteroids are the mainstay of therapy.

  • Topical therapy with prednisolone acetate 1% or prednisolone sodium phosphate 1% is only helpful in the treatment of the anterior segment inflammation. The intravitreal concentration of corticosteroids administered topically is too low to be efficacious in the face of moderate-to-severe vitritis, especially in the phakic patient.

  • Periocular injections of corticosteroids are preferentially given in unilateral cases and occasionally in bilateral cases. Triamcinolone acetonide can be administered superotemporally into the sub-Tenon space or through the inferior eyelid into the retroseptal space. If the disease is not controlled after 2-3 injections given over an 8-week period, systemic prednisone should be considered. Some authorities advocate the use of a combination of betamethasone and depot methylprednisolone in an effort to achieve early onset and prolonged duration of action.

  • Oral prednisone may be the preferred treatment in patients with bilateral intermediate uveitis or in cases resistant to topical or periocular steroids. A purified protein derivative (PPD) test is imperative prior to starting any patient on systemic corticosteroids if there are any risk factors for TB. Once the inflammation stabilizes, the oral dose is tapered according to disease activity. An H2 blocker (Tagamet or Zantac) or a proton pump inhibitor (Prilosec or Prevacid) can be prescribed adjunctively to oral steroids.

  • Intravitreal triamcinolone acetonide injections have been used to treat CME. In a case series by Hogewind et al, of 33 eyes with intermediate or posterior uveitis and refractory CME, 50% improved greater than 2 lines at 3 months; but, by 12 months, the proportion of improved eyes declined to 40%. ^[9]

  • Several small case series have explored the use of somatostatin analogues (Octreotide) IM and intravitreal bevacizumab (Avastin) in patients with refractory uveitic CME.

  • For recalcitrant cases with high corticosteroid requirements to control the inflammation, the surgical implantation of a device releasing fluocinolone acetonide in the vitreous can be considered (see Surgical Care).

• In the event that corticosteroids cannot control the intermediate uveitis or in those whose disease invariably flares when steroids are discontinued, immunosuppressive therapy often is attempted. Immunosuppression or immune-modulation is also used as part of the concept of steroid-sparing therapy in an effort to reduce the patient's requirement for systemic corticosteroids and, therefore, to diminish the adverse effects of systemic corticosteroid therapy.

  • Methotrexate, mycophenolate, cyclosporine, tacrolimus and azathioprine, are the most commonly used agents with documented efficacy in many uveitic conditions. Chlorambucil can be considered for intractable cases but is rarely required anymore. They can be used concurrently with corticosteroids as steroid sparing agents or alone.

  • Murphy et al prospectively evaluated the efficacy and the safety of cyclosporine and tacrolimus in patients with posterior and intermediate uveitis. ^[10] The 2 agents did show a similar response rate (approximately 67%), but cyclosporine was associated with a higher incidence of adverse effects.

  • Two phase 3 studies (VISUAL 1 and VISUAL 2) showed that adults with active and inactive noninfectious intermediate uveitis, panuveitis, and posterior uveitis treated with adalimumab had a significantly lower risk for treatment failure as compared with placebo. In July 2016, the FDA approved adalimumab as a second-line treatment for patients who do not respond appropriately to steroids, making adalimumab the first noncorticosteroid medication approved for uveitis. Adalimumab is an important addition to the treatment armamentarium in the management of patients with noninfectious uveitis. ^{[11, 12]}

  • The use of infliximab, an anti-tumor necrosis factor (anti-TNF) monoclonal antibody, has been shown to be effective in improving macular thickness and visual acuity in patients with uveitic refractory CME due to intermediate uveitis or other noninfectious uveitis. Initial successful reports by Markomichelakis et al were duplicated by Rajaraman et al in a pediatric population in which infliximab achieved reduction in intraocular inflammation with concurrent elimination or decrease in steroid requirements. ^{[13, 14]}

  • Finally, interferon-beta (INF-beta), which has an established value in the treatment of MS, appears to have a positive effect in terms of visual acuity, CME, and aqueous and vitreous inflammation in intermediate uveitis associated with MS.

Surgical treatment includes the following:

• Cryotherapy has been shown to be effective in treatment of intermediate uveitis. It may be used after periocular or systemic corticosteroid therapy failure and is often combined with a periocular steroid injection. Peribulbar anesthesia is required for this procedure.

  • By ablating the peripheral retina with a transconjunctival approach, compromised vasculature can be destroyed, eliminating both the source for inflammatory mediators and the stimulus for neovascularization.

  • The effect is noted after several weeks but may need to be repeated after 3-6 months.

  • Devenyi et al reported that 90% of steroid-resistant eyes no longer required corticosteroid treatment after cryotherapy, and, in 78%, vitritis was eliminated. ^[15]

  • This surgical approach is not without complications including transient worsening of vitreous inflammation, decreased accommodative potential, cataract, hyphema, epiretinal membranes, and retinal detachment.

  • Therefore, some authors advocate the use of cryotherapy only for patients with peripheral retinal neovascularization and a history of vitreous hemorrhage.

• Park and colleagues evaluated the use of peripheral scatter photocoagulation in 10 eyes with steroid-resistant pars planitis. ^[16] Photocoagulation appeared to be as effective as cryotherapy in controlling intraocular inflammation and neovascularization of the vitreous base.

• Another surgical option for treating intermediate uveitis is pars plana vitrectomy.

  • This modality is gaining popularity, because it theoretically reduces the antigen load and inflammatory mediators in the vitreous.

  • Pars plana vitrectomy has been shown to decrease the intensity of the intraocular inflammation and reduce CME, but controlled clinical trials are lacking.

  • In a published review of 44 interventional case series of pars plana vitrectomy for uveitis, the most common indication of pars plana vitrectomy was intermediate uveitis. This review by Becker et al grades pars plana vitrectomy as possibly relevant to the outcomes of improving vision and reducing inflammation and CME. ^[17]

  • Another small prospective study found that eyes randomized to pars plana vitrectomy/immunomodulatory therapy had improved uveitis compared with those given immunomodulatory therapy alone. ^[18]

  • Retinal detachment, cataract, and recurrent vitreous hemorrhage are known complications. Several authorities reserve the use of vitrectomy for patients with either dense vitreous debris with known complications of intermediate uveitis such as nonclearing vitreous hemorrhage or epiretinal membrane.

  • Vitrectomy also may be indicated in patients who are steroid responders or those who cannot use/tolerate immunosuppressive therapy.

  • In a retrospective analysis, pars plana vitrectomy was combined with cataract surgery in 22 of 43 eyes with intermediate uveitis; 40 of 43 eyes achieved a similar or better visual acuity after an average follow-up period of 45 months. In a small subset, immunosuppression could also be discontinued.

• For cases that require a high dose of systemic corticosteroids or frequent periocular injections to control flare-ups of the disease, the surgical implantation of a fluocinolone acetonide (Retisert, Yutiq) or dexamethasone (Ozurdex) implant can be considered. In a cohort of patients with recurrent posterior noninfectious uveitis, where the more severely affected eye was selected to receive a fluocinolone implant, the selected eyes showed a significant decrease in disease recurrences, from 51.4% to 6.1%, after 34 weeks of follow-up, with a moderate benefit in visual acuity as well. ^[19] In addition, in a randomized trial, the 0.7-mg dexamethasone implant effectively reduced intraocular inflammation and improved visual acuity over a 6-month period. ^[20]

• Many patients with intermediate uveitis develop cataract, either secondary to the disease process or due to corticosteroid treatment.

  • Management of cataract in these patients is controversial.

  • It is well established that maximal preoperative suppression of inflammation is imperative before cataract surgery. Younger patients should be cell free for 6 months prior to surgery, and older patients for at least 3 months, depending upon the judgment of the experienced operating surgeon.

  • The controversy lies in whether these patients would benefit more from aphakic correction or intraocular lens (IOL) placement.

  • Some authors report a poor visual outcome secondary to a postoperative escalation of inflammation and/or adherent debris onto the IOL, requiring multiple YAG laser procedures.

  • Other investigators have found that select patients can enjoy a relatively uncomplicated postoperative course and improved visual acuity with pseudophakia.

  • Although it was speculated that heparin surface-modified intraocular lenses would reduce postoperative debris collection and posterior synechiae, small prospective case series suggest that there is no statistical difference between heparin-coated IOLs and polymethyl methacrylate (PMMA) IOLs in terms of final visual acuity, lens deposits, posterior capsular opacities, or anterior/posterior synechiae.

  • In a retrospective series of 86 patients (100 eyes) with pars planitis who underwent phacoemulsification, 91% had better visual acuity postoperatively and only 10% had a decrease in visual acuity as a result of reactivation of pars planitis or progression of CME. This study determined that acrylic IOL had a statistically significant lower incidence of posterior capsular opacification compared to PMMA IOLs.

A cost-effective, directed, patient-specific laboratory diagnostic evaluation is best directed by the informed ophthalmologist. This approach incorporates the demographics, history, and examination findings into a comprehensive, practical diagnostic approach to the patient with uveitis.

For any patient with uveitis, seek an internist for a general medical evaluation.

Input from a gastroenterologist, neurologist, or infectious disease specialist may be necessary, depending on physical findings or pertinent elements of the review of systems.

Consultation with an experienced chemotherapist is mandatory when using alkylating and cytotoxic agents.