Treatment of Uveitis



Treatment of Uveitis





LOCAL THERAPY

Sam S. Dahr

Local therapy of uveitis consists of topical drops, periocular injections, and intravitreal modalities, including injections and implants.


TOPICAL THERAPY


Prednisolone and Difluprednate

• Prednisolone acetate 1% ophthalmic suspension is a commonly used steroid eye drop marketed under the brand names Pred-Forte, Econopred, and Omnipred. Numerous generic formulations are also available.

• Difluprednate ophthalmic emulsion 0.05% (Durezol) was Food and Drug Administration (FDA) approved in 2008 for the treatment of inflammation and pain associated with ocular surgery.



  • It is considered at least as effective as prednisolone acetate 1%, and some evidence suggests that it is approximately twice as effective.


  • Unlike prednisolone acetate, which is a suspension, difluprednate does not require shaking, and because of its higher potency, it may allow for a less frequent dosing regimen.


Indication and Dosing

• Topical drops should be used to treat anterior uveitis. It may also be used to treat the anterior component of uveitis that also affects the intermediate or posterior compartments. Drops should not be used as monotherapy for intermediate uveitis, posterior uveitis, or panuveitis.

• The drops should be dosed according to the disease activity and can be used as frequently as every half hour while awake.

• Brand name Pred-Forte may be more effective than generic prednisolone acetate 1%.

• The goal is to eliminate the anterior chamber cell activity whenever possible.

• A common regimen is to taper by 1 drop per week, but tapering should not occur until the eye is inflammation free (if able to be achieved within a reasonable period of time). Eyes with intermediate uveitis, posterior
uveitis, or panuveitis on systemic therapy may have low-grade inflammatory breakthroughs in the anterior chamber only. In lieu of increasing systemic therapy, difluprednate or prednisone acetate 1% administered infrequently (one drop two or three times a week, e.g., Monday-Wednesday-Friday schedule or a Tuesday-Thursday schedule) may suppress these anterior breakthroughs while minimizing intraocular pressure (IOP)-related issues.


Complications and Side Effects

• The main side effects of topical steroids are an elevated IOP and cataract formation (Fig. 14-1). This risk is likely higher with difluprednate.

• Secondary infections, such as reactivated herpetic keratitis, bacterial keratitis, or fungal keratitis, are also possible side effects.

• Patients should not use contact lenses while using topical steroid therapy.


Cycloplegics and Mydriatics

• Cycloplegics and mydriatics, such as tropicamide, cyclopentolate, scopolamine, homatropine, and atropine, dilate the pupil and can prevent the development of posterior synechiae and may ameliorate pain associated with ciliary body inflammation and spasm.


Indication and Dosing

• It can be used for all cases with significant anterior chamber inflammation or eye pain suggestive of ciliary body spasm.

• Usually, shorter acting agents, such as tropicamide, provide a few hours of dilation followed by subsequent pupillary constriction. Three times a day dosing allows several cycles of dilation and constriction during a 24-hour period; by keeping the pupil moving, posterior synechiae development is reduced.

• Eyes with darker irides or higher levels of inflammation may require stronger/longer acting agents, such as scopolamine, homatropine, or atropine, both to facilitate the dilation/constriction cycle and to relieve ciliary pain.

• Some pupillary motility should be encouraged. If the pupil is immobile while dilated, posterior synechiae can still form.


Complications and Side Effects

• These medications are anticholinergics; thus, they may induce dryness of the mouth, facial flushing, headache, and, rarely, vasomotor or cardiorespiratory disturbances. Patients at risk of such complications may be advised to perform nasolacrimal occlusion for 1 minute after drop instillation.


PERIOCULAR THERAPY


Triamcinolone

• Triamcinolone acetonide is an injected long-acting steroid suspension, obtained under the brand names Kenalog or Kenalog-40.

• Kenalog has been used for periocular injections in an off-label manner for decades.


Indication and Dosing

• It is useful for all types of intraocular inflammation: anterior uveitis, intermediate uveitis, posterior uveitis, and panuveitis, as well as uveitic macular edema.

• Transconjunctival, transdermal, anterior sub-Tenon’s, and posterior sub-Tenon’s (Nozik style) injection techniques may be used.

• Typically, 40 mg (usually in 1 mL) is given, although 20 mg/0.5 mL may be used for an anterior sub-Tenon’s injection.


Complications and Side Effects

• The most feared complication is inadvertent ocular penetration.

• Patients may develop ptosis, even after a single injection.


• Septal atrophy with protuberance of the lower eyelid may also occur.

• Increased IOP and cataract may occur months or even years later, so patients need to have regular IOP measurements.

• A triamcinolone injection may increase the risk of secondary infections, and contact lens use should be discouraged.

• Chorioretinal scars suggestive of previous Toxoplasma infection and a positive Toxoplasma serum immunoglobulin G (IgG) titer are a strong relative contraindication to steroid injection.







FIGURE 14-1. Posterior subcapsular cataract. This patient developed a posterior subcapsular cataract, both as a result of her uveitis and from periocular steroid injections. (Courtesy of Julia Monsonego, CRA.)



INTRAVITREAL THERAPY


Triamcinolone

• Triamcinolone acetonide is an injectable long-acting steroid suspension.

• Triesence (Alcon) is preservative free and FDA labeled for intraocular use in uveitis and ocular inflammatory conditions.

• Preservative-free triamcinolone can be obtained from some compounding pharmacies.


Indication and Dosing

• It can be used in cases of intermediate uveitis, posterior uveitis, and panuveitis, as well as in cases of uveitic cystoid macular edema, in cases in which systemic therapy is insufficient and/or contraindicated.

• Historically, a 4 mg dose was utilized; however, recent experience suggests 1 to 2 mg is as effective as with a lower rate of IOP increase and less cataract formation.


Side Effects

• Patients may develop:



  • True infectious endophthalmitis


  • A paradoxic noninfectious inflammatory response to the drug (“sterile endophthalmitis”)


  • A “pseudoendophthalmitis” caused by triamcinolone particles settling in the anterior chamber and appearing as a hypopyon

• Increased IOP and cataract may occur months or years later.

• As with sub-Tenon’s steroid injection, when possible, periocular steroid injection should be avoided in eyes with a previous Toxoplasma infection and a positive Toxoplasma serum IgG titer.


Ranibizumab and Bevacizumab

• Ranibizumab (Lucentis), aflibercept (Eylea), and bevacizumab (Avastin) are genetically engineered monoclonal antibodies that bind to and inhibit the biologic activity of human vascular endothelial growth factor (VEGF). Ranibizumab is FDA approved for intraocular injection to treat wet macular degeneration, macular edema associated with retinal vein occlusion, diabetic macular edema (DME), diabetic retinopathy, and myopic choroidal neovascularization. Aflibercept is FDA approved for wet macular degeneration, macular edema following vein occlusion, DME, and diabetic retinopathy in patients with DME. Bevacizumab is FDA approved for intravenous (IV) use for various forms of cancer; the intraocular use of bevacizumab is off label, but its use is clinical trials validated and well established.


Indication and Dosing

• Anti-VEGF therapy may be used in conjunction with steroid therapy (usually sub-Tenon’s or intravitreal triamcinolone) for inflammatory choroidal neovascularization associated with white dot syndromes, sarcoidosis, and other forms of uveitis. It is also useful for peripheral retinal and anterior segment neovascularization.

• Although anti-VEGF therapy may be considered for patients with uveitic macular edema unresponsive to steroid and steroid-sparing therapy, any effect tends to be mild and transient, with a need for repeated injections over time. Therefore, anti-VEGF treatment should not be considered first-line therapy for uveitic macular edema.

• The typical dosing is a 0.05-mL injection of ranibizumab 0.5 mg, aflibercept 2 mg, or bevacizumab 1.25 mg.


Complications and Side Effects

• The standard potential complications of an intravitreal injection apply.

• Rarely, anywhere from days to weeks after an injection, patients may develop a mild inflammatory response with anterior chamber
and vitreous cells but without significant vitreous haze.


Fluocinolone Implant (Retisert)

• The fluocinolone acetonide 0.59 mg intravitreal implant is a long-acting implant marketed under the name Retisert. It is inserted through a pars plana incision performed in the operating room (Fig. 14-2).


Indication and Dosing

• The FDA label states that the fluocinolone implant is indicated for the treatment of chronic noninfectious uveitis affecting the posterior segment of the eye. In terms of the Standardization of Uveitis Nomenclature (SUN) classification, the implant can be used to treat significant intermediate uveitis, posterior uveitis, or panuveitis.

• The fluocinolone implant may be especially useful for unilateral disease or for patients who are intolerant of systemic immunomodulatory therapy (IMT). In patients previously on systemic steroid-sparing therapy, the fluocinolone implant does not necessarily eliminate a patient’s need for such therapy, but may allow dose reductions during the life of the implant.

• The 0.59-mg implant releases fluocinolone acetonide for approximately 30 months. Another implant can be placed without removing the previous implant, or the previous implant can be removed and exchanged.


Side Effects

• The fluocinolone implant shares all the potential complications of a vitreoretinal procedure, including endophthalmitis and hemorrhage.

• In the phase III trials, 60% of patients needed IOP-lowering therapy, and at 2 years, 32% of patients needed glaucoma filtering surgery. Greater than 90% of phakic eyes needed cataract surgery by 2 years postimplantation.

• The Multicenter Uveitis Steroid Treatment Trial compared the fluocinolone implant to systemic IMT. Fifty-four-month data suggest similar visual acuity, inflammatory control outcomes, and quality of life outcomes but there was some loss of visual benefit at 7 years compared to systemic therapy. However, the implant arm showed significant local complications, including need for cataract surgery, as well as ocular hypertension or glaucoma with the need for ocular hypertensive therapy and IOP-lowering surgery. Particularly for bilateral disease, systemic therapy may be a better first choice given its efficacy, systemic safety, and ocular safety.

• Over time there is a risk of implant dissociation, where the drug pellet separates from the strut. This event may occur spontaneously or during removal/exchange surgery.


Dexamethasone Implant (Ozurdex)

• The dexamethasone implant (Ozurdex) is a solid polymer drug delivery system containing 0.7 mg of micronized dexamethasone.

• The rod-shaped implant is injected in an office procedure into the vitreous through the pars plana utilizing a 22-gauge single-use injector/applicator. The implant is preservative free and will completely biodegrade over time.

May 5, 2019 | Posted by in OPHTHALMOLOGY | Comments Off on Treatment of Uveitis
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