Classification of uveitis

Summary

Uveitis is defined as inflammation of the uveal tract (the iris, ciliary body and choroid), and in some cases the surrounding structures (retina, vitreous or anterior chamber). In this article, we describe the classification of uveitis by it’s anatomical location.

Anatomy

As the uveal tract is made up of the iris, ciliary body, and choroid, we’ll first dive in to the anatomy of the region. Check out our anatomy section for the detailed anatomy!

Iris

The iris is the most anterior part of the uvea, consisting of two parts, the 1) stroma, and 2) posterior pigmented layer.

Ciliary body

The ciliary body consists of 1) the stroma, 2) muscle, and 3) epithelium. It is divided into two parts, the pars plicata anteriorly and the pars plana which lies more posteriorly.

1. the pars plana: an avascular flat (plana = flat) portion between the ora serrata and ciliary processes of the pars plicata.

2. the pars plicata: a highly vascularised folded layer which forms an attachment for lens zonules

💡 As it is avascular, the pars plana is a good site for intravitreal injections or vitreous removal (you may have heard of pars plana vitrectomy)

Choroid

The choroid is the layer which lies between the sclera and the retinal pigment epithelium. It provides nutrients to the outer layers of the retina, and is perfused via two long posterior ciliary arteries, (short posterior ciliary artery and anterior ciliary artery) It is made of two layers:

1. Bruch’s membrane: this is the innermost layer, it’s function is unclear however it may play a part in fluid transport from the choroid to the retina, and is also permeable to fluoroscein

2. Vascular layer: this is split up into the choriocapillary layer, a medium vessel layer, and a large vessel layer

Classification table

The Standardisation of Uveitis Nomenclature (SUN) Working Group guidance on uveitis terminology, endorsed by the International Uveitis Study Group (IUSG), categorises uveitis anatomically:

	Area affected	Types
Anterior Uveitis	Iris +/- pars plicata	Iritis, Iridocyclitis Anterior cyclitis
Intermediate Uveitis	Pars plana and vitreous	Pars planitis, hyalitis Posterior cyclitis
Posterior Uveitis	Choroid and retina	Chorioretinitis, retinitis, neuroretinitis
Pan-uveitis	All of the above

Anterior uveitis

Anterior uveitis refers to inflammation of the iris and pars plicata (the anterior part of the ciliary body). The commonest presentation you will have come across is acute anterior uveitis, particularly associated with HLA-B27 associated conditions.

Clinical features

• The hallmark features are pain, redness, photophobia

• Anterior chamber cells

• Aqueous flare (with inflammation, proteins seep out of leaky blood vessels into the anterior chamber fluid)

• Iris nodules (Busacca and Koeppe nodules)

• Hypopyon

• Posterior synechiae (adhesions where the iris adheres to the anterior lens capsule, resulting in an irregular pupil which is sluggish in it’s reaction to light)

• Complications such as cystoid macular oedema, band keratopathy and secondary glaucoma

Slit-lamp photograph with TINU syndrome (Tubulointerstitial Nephritis and Uveitis Syndrome) showing ciliary injection, granulomatous keratic precipitates, and an irregular pupil. Image courtesy of Barut et al.

Acute and chronic

It can be of acute or chronic (>3 months) onset, however the commonest presentation of anterior uveitis is acute anterior uveitis - AAU. AAU typically has a sudden onset and a limited duration, with symptoms that usually quickly resolve with anti-inflammatory therapy. For the uveitis to be of a limited duration, inflammation must not recur for at least 3 months following tapering of steroids. In chronic disease however, inflammation typically will recur as soon as anti-inflammatory therapy is stopped.

Granulomatous and non granulomatous

Anterior uveitis can also be divided into granulomatous (due to underlying granuloma-forming disease), and non-granulomatous causes.

• Granulomatous

• Usually a chronic form of uveitis and is due to granuloma-forming underlying disease

• Examples include sarcoidosis, tuberculosis, syphilis

• Specific features include ‘mutton fat’ keratic precipitates

• Busacca nodules (only seen in granulomatous) and Koeppe nodules (also seen in non-granulomatous). These are inflammatory cell precipitates, Busacca nodules lie on the iris surface whilst Koeppe nodules lie on the pupillary margin

• Non Granulomatous

• Fine ‘Stellate’ keratic precipitates

• Koeppe nodules only

Causes split up by aetiology:

Idiopathic
HLA-B27 associated	Psoriasis, reactive arthritis, IBD, ankylosing spondylitis
Inflammatory	Sarcoidosis, Behçet's disease, SLE, juvenile idiopathic arthritis, multiple sclerosis, Fuch’s heterochromic cyclitis, tubulointerstitial nephritis, Posner-Schlossman syndrome
Infectious	TB, Lyme disease, syphilis, varicella zoster

Management

Acute management: steroid drops (e.g. prednisolone acetate 1%) and cyclopentolate

The basic workup for acute anterior uveitis includes HLA-B27 and syphilis testing. For bilateral granulomatous disease one should also consider testing for sarcoid (CXR at least).

A: Koeppe nodules at the pupillary border and Busacca nodules in the iris stroma in a Fuchs’ uveitis syndrome. Image courtesy of Nalçacıoğlu et al. B: Slit lamp photograph showing the granulomatous anterior uveitis with large Koeppe nodules. Image courtesy of Babu et al. C: Small stellate non-gravitationally distributed keratic precipitates (KPs) typical of Fuchs' uveitis. Image courtesy of Herbort et al. D: Mutton-fat KPs: This type of gravitational large KPs can be seen in tuberculosis and sarcoidosis, Image courtesy of Herbort et al.

Intermediate uveitis

Intermediate uveitis is inflammation of the posterior ciliary body (pars plana) and vitreous. This is a rarer form of uveitis. It is rarer than other forms, and is typically painless with no red eye. It’s onset is also usually insidious and bilateral.

Clinical features:

• Slow onset, bilateral

• Blurred vision

• Floaters

• Painless, no red eye

• Snowballs: white focal inflammatory cells and exudates

• Snowbanking: white exudates on the ora serrata which may extend onto the pars plana

• Peripheral periphlebitis: strong association with multiple sclerosis!

Causes split up by aetiology:

Idiopathic	Pars planitis
Inflammatory	Sarcoidosis, MS, inflammatory bowel disease
Infectious	Lyme disease, Toxocariasis, Whipple’s disease, Syphilis, Leprosy

Complications

• CMO - much more common in intermediate uveitis, complicating up to 50% of cases

• Optic disc swelling

• Band keratopathy (complicating up to 40% of cases!)

• Glaucoma

• Cataract formation

Pars plana snowball exudates. Image Courtesy of Babu et al.

Posterior uveitis

Posterior uveitis is inflammation of the choroid +/- retina. It is the rarest form of uveitis, and the most likely to result in vision loss. Whilst some cases may be asymptomatic, others may have a sudden onset with acute deterioration.

Clinical features:

• Floaters

• Reduced visual acuity

• Blurred or lost vision

• Difficulty seeing in the dark

• Difficulty seeing colour

Idiopathic
Inflammatory	Sympathetic ophthalmia, Vogt-Koyanagi-Harada (VKH) syndrome, birshot choroidopathy, sarcoidosis, Behcet’s
Infectious	Toxoplasmosis, onchocerciasis, toxocariasis, syphilis, TB, VZV, HSV, CMV

💡 While anterior uveitis often causes a painful red eye, light sensitivity and blurred vision, the symptoms of posterior uveitis are more subtle. As we go further back in the eye from anterior to posterior, inflammation is more likely to result in visual loss as the retina/choroid is affected.

References

1. Salmon, John F., and Jack J. Kanski. Kanski’s Clinical Ophthalmology: A Systematic Approach. Ninth Edition, Elsevier, 2020

2. Elnahry, Ayman G., and Gehad A. Elnahry. ‘Granulomatous Uveitis’. StatPearls, StatPearls Publishing, 2022. PubMed, http://www.ncbi.nlm.nih.gov/books/NBK570581/

3. Gilani, Christopher J., et al. ‘Differentiating Urgent and Emergent Causes of Acute Red Eye for the Emergency Physician’. Western Journal of Emergency Medicine, vol. 18, no. 3, Apr. 2017, pp. 509–17. PubMed Central, https://doi.org/10.5811/westjem.2016.12.31798.

4. Nalçacıoğlu, Pınar, et al. ‘Clinical Characteristics of Fuchs’ Uveitis Syndrome’. Turkish Journal of Ophthalmology, vol. 46, no. 2, Apr. 2016, pp. 52–57. PubMed Central, https://doi.org/10.4274/tjo.99897.

5. Babu, Kalpana. ‘Sarcoidosis in Tuberculosis-Endemic Regions: India’. Journal of Ophthalmic Inflammation and Infection, vol. 3, no. 1, June 2013, p. 53. PubMed, https://doi.org/10.1186/1869-5760-3-53.

6. Herbort, Carl P. ‘Appraisal, Work-up and Diagnosis of Anterior Uveitis: A Practical Approach’. Middle East African Journal of Ophthalmology, vol. 16, no. 4, Oct. 2009, pp. 159–67. PubMed, https://doi.org/10.4103/0974-9233.58416.

7. Barut, Kenan, et al. ‘Acute Granulomatous Iridocyclitis in a Child with Tubulointerstitial Nephritis and Uveitis Syndrome’. Journal of Ophthalmic Inflammation and Infection, vol. 5, Feb. 2015, p. 3. PubMed Central, https://doi.org/10.1186/s12348-015-0035-2.