YO Clinic July 2021

UVEITIS: GENERAL APPROACH

Uveitis is inflammation of the uvea (in Latin uva, means ‘grape’) which consists of the pigmented layers of the eye, mainly the iris, ciliary body and choroid. Inflammation of these structures may involve the retina, sclera, cornea, vitreous and optic nerve.

Uveitis is responsible for 5-10% of visual impairment worldwide. Up to 35% of uveitic cases end up with significant visual loss. Prognosis varies by age, etiology and type of inflammation. In general, females are slightly more affected. Non-infectious etiology is generally more common in the developed world, whereas, recently, the prevalence of infectious etiologies, including TB and syphilis, has increased.

A comprehensive ophthalmic and systemic evaluation is essential because uveitis is frequently associated with systemic diseases. Furthermore, determining the type of inflammation guides our therapeutic approach. 

There are various classification systems based on anatomy, clinical course, etiology and histology of the inflammation. In order to create standardized terminology, the Standardization of Uveitis Nomenclature (SUN) Working Group developed an anatomical classification system, descriptors and grading system in 2005 (Table 1). 

Table 1: The SUN Working Group Anatomical Classification and Descriptors in Uveitis

Uveitis Type	Primary Inflammation Site                                 Include
Anterior uveitis	Anterior Chamber	Iritis, Iridocyclitis, Anterior cyclitis
Intermediate uveitis	Vitreous	Pars planitis, Posterior cyclitis, Hyalitis
Posterior uveitis	Retina or choroid	Choroiditis, Chorioretinitis, Retinochoroiditis, Retinitis, Neuroretinitis
Panuveitis	Anterior chamber, vitreous,retina/choroid
Category	Descriptor	Comment
Onset	Sudden Insidious
Duration	Limited Persistent	≤3 months duration >3 months duration
Course	Acute Recurrent Chronic	-Sudden onset limited duration -Repeated episodes, inactivity without treatment >3 months -Relapse in <3 months after  discontinuation of treatment

1. Anterior Uveitis

Inflammation of the iris (iritis) and ciliary body (cyclitis) accounts for nearly 45-50% of all uveitis cases. Anterior uveitis in adults is most commonly idiopathic, however other causes are HLA-B27 associated diseases (ankylosing spondylitis, Reiter’s syndrome, psoriatic arthritis and inflammatory bowel disease).

The two main subgroups are non-granulomatous and granulomatous uveitis. Acute non-granulomatous inflammation might be idiopathic or associated with autoimmune diseases, infections, trauma or drug use. Meanwhile, chronic non-granulomatous uveitis (>6 weeks) might be due to juvenile idiopathic arthritis (JIA), Fuchs’ heterochromic iridocyclitis and infections.

Granulomatous uveitis might also have an infectious origin or might be immune-mediated as in sarcoidosis, Vogt-Koyanagi-Harada (VKH) syndrome, sympathetic ophthalmia, MS and lens-induced uveitis.

Symptoms and signs depend on which part of the uvea is involved, time of onset and duration of the disease. Acute onset anterior uveitis might cause pain, photophobia, redness, blurred vision and epiphora. Typical findings are conjunctival and ciliary injection, miosis, anterior chamber reaction and keratic precipitates. On the other hand, chronic anterior uveitis, e.g. JIA, might present without any symptoms. The presenting symptom may be blurred vision due to complications such as calcific band keratopathy, cataracts and cystoid macular edema (CME). Other possible causes of blurred vision are inflammatory cells in visual axis, fibrin, aqueous flare and keratic precipitates. Hypopyon, synechiae and iris nodules (Koeppe nodules; at the pupillary border, Busacca nodules; in iris stroma, Berlin nodules; in the angle) might be noted too. Intraocular pressure might be either low due to decreased aqueous production or high due to trabeculitis and decreased outflow.

2. Intermediate Uveitis

Intermediate uveitis accounts for up to 15% of all uveitis cases. Here, the primary inflammation sites are vitreous, vitreous base over the ciliary body and peripheral retina-pars plana complex.

Intermediate uveitis might be seen in MS, sarcoidosis, syphilis and TB. The most common form (85-90%) is pars planitis, in which ‘snowball’ or ‘snowbanking’ occurs without any sign of infection or systemic disease.

Floaters and blurred vision are the most common presenting symptoms. Those might be due to vitreous cells and/or CME. The onset in teenagers might be more insidious. Ischemia from retinal phlebitis may lead to neovascularization along the areas of snowbank in 10%. 

Although 60% of cases have a prolonged course and 30% of cases have a course with remissions and exacerbations, CME could be resolved with adequate anti-inflammatory control with a good visual prognosis.

3. Posterior Uveitis

Posterior uveitis primarily involves the retina and/or choroid and constitutes approximately 20% of all uveitic cases. The most common cause in adults is toxoplasmosis.

Etiology might be infectious as in toxoplasmosis, CMV, acute retinal necrosis, candidiasis or cat-scratch disease. A subgroup of inflammatory chorioretinopathies, known as ‘white dot syndromes,’ are described, commonly present with discrete, multiple, well-circumscribed, yellow-white lesions at the retina level, retina pigment epithelium (RPE) and choroid. Bilateral involvement, female predominance and young age (<50 years) are common features. Fluorescein angiography, fundus autofluorescence, indocyanine green angiography and optical coherence tomography help during diagnosis and treatment selection. 

Presenting symptoms include painless decrease in visual acuity, floaters, photopsia, scotomata, metamorphopsia and nyctalopia. Vitreous cells, membranes, vasculitis (sheathing, cuffing), exudates, pigmentary changes (due to RPE inflammation) and choroiditis might be observed. 

4. Panuveitis

In panuveitis or diffuse uveitis, the inflammation involves all anatomical compartments of the eye. It is usually bilateral yet might be asymmetrical. Etiology might be associated with systemic diseases as sarcoidosis, Behçet’s disease, VKH syndrome, syphilis or TB. Penetrating eye trauma might cause panuveitis in sympathetic ophthalmia. Generally, systemic findings help the differential diagnoses because ocular findings are varied. In Behçet’s disease, recurrent, usually bilateral, non-granulomatous anterior or posterior uveitis, conjunctivitis, episcleritis and keratitis might be seen. However, bilateral diffuse granulomatous panuveitis with serous retinal detachments are characteristic in VKH. Sarcoidosis is a multisystem granulomatous disease with recurrent granulomatous anterior uveitis episodes in which pars planitis, retinal periphlebitis and choroiditis might be seen. 

5. Management: General Principles

The primary aim of therapy is to control inflammation and reduce the risk of vision loss. The treatment protocol should be shaped according to the etiology. The main constituents are topical steroids and cycloplegics. In case of an infection, antibiotics are added as well. Systemic steroids and immunosuppressive agents might be used in refractory cases. Anti-VEGF therapy in the case of CME and choroidal neovascular membrane should be used to protect visual function. Pars plana vitrectomy might be considered in vision-threatening and severe cases.

Immune-mediated eye diseases are a leading cause of visual disability worldwide. Appropriate differential diagnoses, familiarity with the therapeutic approaches and recognizing and treating vision threatening complications are all crucial in daily practice.

YO News – July