POSTERIOR UVEITIS

Signs and Symptoms

Posterior uveitis is an encompassing term indicating inflammation of the posterior segment. The inflammation may be posterior, intermediate or pan-ocular. As the causes of posterior uveitis are numerous, so are the signs and symptoms. Patients with posterior uveitis typically complain of vision reduction, floaters and possibly visual field loss. Pain, photophobia and lacrimation, typical of anterior uveitis, are usually absent in cases of posterior uveitis. Due to the myriad potential causes, there is no identifiable age, sex or racial predilection. However, for each cause of posterior uveitis, there may be a racial, gender or age predominance.

Posterior uveitis is a set of conditions that can be broadly ascribed to either an infectious or noninfectious inflammatory cause. As such, patients may have a preexisting diagnosis of an infectious disease such as histoplasmosis, toxoplasmosis, toxocariasis, syphilis, tuberculosis, herpes simplex, herpes zoster, cytomegalovirus, West Nile virus, Dengue fever, Chikungunya, Rift Valley fever, rickettsioses or bacterial or fungal septicemia. Alternately, patients may suffer from a diagnosed inflammatory condition such as Behçet syndrome or sarcoidosis. Patients with no known medical conditions may manifest posterior uveitis as the initial marker of an infectious or inflammatory condition.1-8

Clinical findings vary depending upon the cause of posterior uveitis and may include vitritis, posterior vitreous detachment (PVD), cystoid macular edema (CME), retinal and anterior segment neovascularization, cataract, serous retinal detachment, retinal hemorrhage, vitreous hemorrhage, chorioretinitis, vasculitis, solitary tumor-like masses, retinochoroidal punctate or plaque-like lesions, retinitis and neuroretinitis, granulomas, occlusive retinal vasculitis, optic neuritis, choroidal and retinal infiltration, inflammatory exudates (“snowballs” and “snow banks”), and “candle-wax drippings” adjacent to retinal vessels, to name a few.1-8

Pathophysiology

Like virtually all inflammations within the body, posterior uveitis in its most basic form represents an antigen-antibody response. Infectious agents such as tuberculosis, syphilis and herpes viruses are the antigenic stimuli. In noninfectious posterior uveitis, various conditions can initiate an autoimmune response where the body reacts to its own tissues. There has been research and speculation regarding the underlying pathophysiology of posterior uveitis with regard to the mechanisms producing inflammatory cell damage to the retina. Inflammatory CD4 T-cells, effector macrophages and proinflammatory cytokines have been implicated, disrupting immune privilege in the posterior segment of the eye.9

Management

A thorough history may identify a potential etiology of posterior uveitis or, at minimum, direct a tailored medical evaluation. A crucial initial part of managing patients with posterior uveitis is determining if the cause is infectious or inflammatory. Infectious causes of posterior uveitis respond well to disease-specific oral or intravenous antimicrobial therapy. Once an infectious cause has been eliminated, inflammatory posterior uveitis can be treated with oral, intravenous or intraocular immunosuppressive anti-inflammatories.10 However, if systemic or intraocular steroids are employed in cases of infectious posterior uveitis without concurrent antimicrobial therapy, the immunosuppression can significantly worsen the condition.

Many cases of posterior and intermediate uveitis—such as toxoplasmosis, pars planitis, histoplasmosis and retinal white dot syndromes (acute posterior multifocal placoid pigmentary epitheliopathy or birdshot choroidopathy)—can be diagnosed ophthalmoscopically. However, conditions such as syphilis and sarcoidosis may present with nonspecific findings of posterior inflammation; the definitive diagnosis must be made through laboratory investigations.

Whenever possible, a medical evaluation tailored towards the most likely causes based upon the clinical examination, the patient’s systemic signs and symptoms and epidemiology should be undertaken. Depending on the suspected etiologies, medical evaluation may include venereal disease research labs, rapid plasma reagin, fluorescent antibody absorption testing, anti-toxoplasma enzyme linked immunoassay titers, tuberculin skin test, chest X-ray and angiotensin converting enzyme.1,8

Should an infectious cause of posterior uveitis be discovered, appropriate systemic antimicrobial therapy can be employed as follows:

For toxoplasmosis, recommended treatments include Daraprim (pyrimethamine, GlaxoSmithKline) and sulfadiazine or Bactrim (trimethprim/sulfamethoxazole (Hoffmann-LaRoche) for four to six weeks. For cases of posterior uveitis caused by syphilis, IV aqueous penicillin G is recommended. Should tuberculosis be identified, possible treatments include isoniazid, Rifadin (rifampin, Aventis), pyrazinamide and Myambutol (ethambutol, X-GEN Pharmaceuticals) for up to seven months. Some, including the military, recommend or require nine-month treatment courses. Care must be taken when using these agents as toxic optic neuropathy may ensure. Viral causes are treated with oral Zovirax (acyclovir, Delcor Asset), Valtrex (valacyclovir, GlaxoSmithKline) or IV ganciclovir. There is no well identified treatment for toxocariasis.1,8

Should infectious causes be ruled out and the condition is considered strictly inflammatory, then systemic anti-inflammatory therapy is employed. Sustained-release intraocular corticosteroid treatment has shown to be an effective strategy for the treatment of noninfectious posterior uveitis. Currently, there are three approved sustained-release intraocular corticosteroid implants: Ozurdex (dexamethasone, Allergan), Retisert (fluocinolone acetonide, Bausch + Lomb) and Iluvien (fluocinolone acetonide, Alimera Sciences).11-17 These sustained-release intraocular implants have been shown to be very effective in controlling inflammation and improving visual acuity in eyes with noninfectious posterior uveitis.11-17

An alternative to sustained-release corticosteroids has always been systemic steroids and other immunosuppressants. The drawback to systemic therapy is that it is nonspecific; long-term use of some of these agents may induce significant adverse effects.18 However, it has been shown that systemic corticosteroids plus immunosuppression for noninfectious intermediate, posterior and panuveitis is effective and well tolerated.19 While sustained-release corticosteroid implants largely avoid systemic adverse effects, they do carry the risk of cataract and elevated intraocular pressure with subsequent glaucoma.20 However, the intensive, site-specific anti-inflammatory action of sustained-release implants may have better ability to control inflammation in posterior uveitis.21

Clinical Pearls

Many conditions that cause posterior uveitis, including toxoplasmosis and the white dot syndromes, can be diagnosed ophthalmoscopically. However, many patients present with nonspecific findings such as vitritis and vasculitis where the diagnosis is not evident. In all cases, medical evaluation is necessary.

Infectious etiologies of posterior uveitis must be eliminated before systemic or intraocular steroid therapy is used.

There is no evidence that topical corticosteroid therapy is effective for posterior uveitis.

Vitritis from posterior uveitis commonly causes PVD. Consider vitritis and posterior uveitis in young PVD patients.

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2. Khairallah M, Kahloun R, Ben Yahia S, et al. New infectious etiologies for posterior uveitis. Ophthalmic Res. 2013;49(2):66-72.

3. Jovanović SV, Jovanović ZD, Radotić FM, et al. Clinical aspects of posterior uveitis in ocular sarcoidosis. Acta Clin Croat. 2012;51(2):247-53.

4. Garweg JG, Tappeiner C. Differential diagnosis in infectious posterior uveitis. Klin Monbl Augenheilkd. 2011;228(4):268-72.

5. Tugal-Tutkun I, Gupta V, Cunningham ET. Differential diagnosis of behçet uveitis. Ocul Immunol Inflamm. 2013;21(5):337-50.

6. Jamilloux Y, Kodjikian L, Broussolle C, Sève P. Sarcoidosis and uveitis. Autoimmun Rev. 2014;13(8):840-9.

7. Davis JL. Ocular syphilis. Curr Opin Ophthalmol. 2014;25(6):513-8.

8. Sudharshan S, Ganesh SK, Biswas J. Current approach in the diagnosis and management of posterior uveitis. Indian J Ophthalmol. 2010;58(1):29-43.

9. Forrester JV. Intermediate and posterior uveitis. Chem Immunol Allergy. 2007;92:228-43.

10. Song J. Systemic management of posterior uveitis. J Ocul Pharmacol Ther. 2003;19(4):325-43.

11. Cabrera M, Yeh S, Albini TA. Sustained-release corticosteroid options. J Ophthalmol. 2014;2014:164692. Epub 2014 Jul 23.

12. Patel CC, Mandava N, Oliver SC, et al. Treatment of intractable posterior uveitis in pediatric patients with the fluocinolone acetonide intravitreal implant (Retisert). Retina. 2012;32(3):537-42.

13. Myung JS, Aaker GD, Kiss S. Treatment of noninfectious posterior uveitis with dexamethasone intravitreal implant. Clin Ophthalmol. 2010; 6(4):1423-6.

14. Sangwan VS, Pearson PA, Paul H, Comstock TL. Use of the fluocinolone acetonide intravitreal implant for the treatment of noninfectious posterior uveitis: 3-year results of a randomized clinical trial in a predominantly Asian population. Ophthalmol Ther. 2014 Dec 12.

15. Lightman S, Belfort R Jr, Naik RK, et al. Vision-related functioning outcomes of dexamethasone intravitreal implant in noninfectious intermediate or posterior uveitis. Invest Ophthalmol Vis Sci. 2013;54(7):4864-70.

16. Lowder C, Belfort R Jr, Lightman S, et al. Ozurdex HURON Study Group. Dexamethasone intravitreal implant for noninfectious intermediate or posterior uveitis. Arch Ophthalmol. 2011;129(5):545-53.

17. Oh EK, Lee EK, Yu HG. Long-term results of fluocinolone acetonide intravitreal implant in Behçet intractable posterior uveitis. Can J Ophthalmol. 2014;49(3):273-8.

18. Pleyer U, Stübiger N. New pharmacotherapy options for noninfectious posterior uveitis. Expert Opin Biol Ther. 2014;14(12):1783-99.

19. Kempen JH, Altaweel MM, Holbrook JT, et al. Multicenter Uveitis Steroid Treatment (MUST) Trial Research Group. Randomized comparison of systemic anti-inflammatory therapy versus fluocinolone acetonide implant for intermediate, posterior, and panuveitis: the multicenter uveitis steroid treatment trial. Ophthalmology. 2011;118(10):1916-26.

20. Friedman DS, Holbrook JT, Ansari H, et al. MUST Research Group. Risk of elevated intraocular pressure and glaucoma in patients with uveitis: results of the multicenter uveitis steroid treatment trial. Ophthalmology. 2013;120(8):1571-9.

21. Pavesio C, Zierhut M, Bairi K, et al. Evaluation of an intravitreal fluocinolone acetonide implant versus standard systemic therapy in noninfectious posterior uveitis. Ophthalmology. 2010;117(3):567-75.