PG Series: Complications of Uveitis

Band keratopathy

• Characterized by deposition of calcium hydroxyapatite in the cornea at the level of Bowman's membrane in long-standing chronic iridocyclitis or intraocular inflammation, especially in children,.
• Starts as at the corneal periphery of the interpalpebral region and typically limited to the interpalpebral zone at the 3 o’clock and 9 o’clock positions.
• Small clear areas, which represent penetration or entry point of corneal nerves into Bowman's layer  give  characteristic "Swiss cheese" appearance.
• Profound band keratopathy can lead to diminution of vision in patients with chronic anterior uveitis, especially in children.

Anterior segment fibrosis and adhesions

Iridolenticular adhesion or synechiae following intense inflammation in anterior chamber is a common complication following recurrent attack of acute anterior uveitis.  

Glaucoma:

Glaucoma is a common complication of uveitis. The incidence of glaucoma is relatively more common in chronic than in acute uveitis.

Based on the aetiopathogenesis, secondary glaucoma in uveitis can be divided into three groups:  secondary open angle glaucoma, secondary angle closure glaucoma and combination of the two. 

Steroid-induced glaucoma

• The therapeutic use of corticosteroids can lead to the rise of intraocular pressure (IOP).
• Increased IOP can occur as a consequence of any form of corticosteroid therapy - oral, intravenous, inhaled, topical, periocular, or intravitreal corticosteroid therapy.
• When treated with topical steroids 20-30% of the population show rise of IOP (steroid responder)
• Children and older patients, patients with pre-existing POAG, glaucoma suspect, or history of POAG in first-degree relative are important risk factors and any form corticosteroid should be used judiciously and under proper monitoring.
• The rise of IOP usually occurs over a period of 4 to 6 weeks when used topically in majority of the patients. It is of paramount importance to understand that there is never a ‘safe’ period in patients on any form of corticosteroid, after which IOP monitoring becomes unnecessary.
• Usually IOP almost always returns to normal within days or weeks of disconnection of the corticosteroid treatment.
• Corticosteroids are believed to induce physical and mechanical changes in the microstructure of the trabecular meshwork causing decreased outflow of aqueous humor.

Corneal Decompensation:

Corneal decompensation in patients with uveitis is rare. It is can be seen in uveitis associated with corneal endothelitis and in herpetic keratouveitis and is a well-recognized feature of chronic cytomegalovirus (CMV) anterior uveitis.

Hypotony/Phthisis

• Long standing inflammation can lead to deposition of exudates and cyclitic membrane over the ciliary body surface leading to diminished function or destruction ciliary processes. This can result into decrease or cessation of aqueous production resulting in hypotony.
• The definition of ocular hypotony is debatable, but it can probably be considered when IOP reduces to less than 6 mmHg.
• Patient experiences diminution in vision mostly due to massive fluctuating astigmatism 
• The collapsing of the scleral wall causes a wrinkling of the choroid and the retina which can be attributed to the cause of hypotonous maculopathy.
• A physical globe often assumes a quadrilateral shape because of the action of four recti muscles on a hypotonous eyeball. 

Cataract:

Cataract formation in uveitic patient can be attributed to   intraocular inflammation or as a side effect of the treatment with corticosteroid. 

Posterior subcapsular cataract are most common, but complicated cataract with nuclear, cortical, and capsular opacities are also seen.  Often they are associated with posterior synechiae and pupillary membranes.

Cataract can also obscure the view of the fundus, making the evaluation of posterior segment very difficult. Also it is very important to determine whether vision loss is due to the cataract or due to some pathologies in posterior segment prior to any surgical intervention.

Cause of cataract in uveitis:

Macular Oedema: 

Cystoid macular oedema (CME) is caused by cystic accumulation of intraretinal fluid in the outer plexiform and inner nuclear layers of the retina because of the breakdown of the blood–retinal barrier.

• CME is one of the major causes of decreased vision in patients with uveitis. It can complicate virtually any type of acute or chronic, anterior or posterior uveitis.
• The exact pathogenesis of uveitic CME remains unclear. Usually CME develops when excess fluid accumulates within the retina of macular region (both extracellularly and intracellularly), which is primarily thought to occur following disruption of the blood-retinal barrier. This fluid accumulation disturbs cell function and retinal architecture. In uveitic eyes, this disruption of blood retinal barrier believed to occur with the release of inflammatory mediators.
• Müller cells function plays an important role in keeping the macula dehydrated in normal condition. Intracellular fluid accumulation in these Müller cells cause significant damage to the metabolic pump action of retina and further reduce macular retinal function. Vitreous traction at the macula also has been proposed as another causative factor for the development of uveitic CME.

Epiretinal membrane:

• Epiretinal membrane (ERM) is an avascular, fibrocellular membrane that proliferates on the inner surface of the retina and can produce various degrees of visual impairment. 

• Long standing intraocular inflammation can lead to ERM formation, surface wrinkling and vitreomacular traction. 
• Epiretinal membranes contain glial cells, retinal pigment epithelial (RPE) cells, macrophages, fibrocytes and collagen fibers. ERM starts as small patchy    areas of reflection from retinal surface which gradually progresses to form irregular, shiny sheet of membrane. In severe cases, it may lead to surface wrinkling and potentially to massive retinal folding.
• Presentation: asymptomatic, decreased visual acuity, metamorphosis, micropsia and macropsia.
• /The severity of symptoms is related to the involvement of macula and the thickness of ERM.
• During biomicroscopical examination of fundus with a +90D or +78D lens, an ERM is seen as a glistening transparent, translucent membrane. Retinal changes associated with ERM can be surface wrinkling, vasculature distortion, cystoid macular oedema or pseudohole. Fundus examination with a blue filter is often helpful.

ERM has been classified into three grades:

Fundus fluorescein angiography (FFA) has a limited role in diagnosis and follow-up of an ERM. Optical coherence tomography (OCT) is very useful to monitor the progression of the membrane.

Retinal Detachment:

Retinal detachment in uveitis can be of

• Exudative (Serous) retinal detachment can present as a part of the inflammatory process e.g. Vogt-Koyanagi-Harada syndrome
• Rhegmatogenous or tractional retinal detachment caused by traction secondary to intraocular inflammation e.g. Acute retinal necrosis syndrome 

• Combined Tractional and rhegmatogenous retinal detachment in Uveitis:

  Abnormal vitreoretinal adhesions and tissue shrinkage are the two important components of retinal detachment in uveitis. In intraocular inflammation abnormal adhesions exist between the vitreous and inflammatory fibrous or neovascular tissue. Shrinkage of fibrous tissue can result in the detachment of retina. Contraction of these fibrous bands can cause a retinal tear which in turn causes a rhegmatogenous detachment.

Retinal ischemia and neovascularization

Intraocular inflammation can affect retinal circulation and sometimes can lead to vascular occlusion (capillary closure and loss of the retinal capillary bed)® Retinal hypoxia® Release of a complex family of stimulatory and inhibitory growth factors from hypoxic retina ® vascular endothelial growth factor (VEGF) [ most important of them]® Retinal angiogenesis

• Neovascularization most frequently arises at the disc or the capillary bed at the edge of an infarcted area of retina, most commonly from the wall of a thickened venule and often begin as a tuft of fine vessels.
• New vessels arising on or within one disc diameter of the optic nerve = neovascularization of the disc (NVD)
• New vessels arising one disc diameter away from the optic disc = neovascularization elsewhere (NVE )
• All these new blood vessels lack barrier properties and rapidly and intensively leak fluorescein during angiography.
• These vessels are sight-threatening because they are fragile and tend to bleed to obscure the media.
• These vessels also associated with fibrosis and membrane formation which can lead to traction retinal detachment.

Choroidal Neovascular Membrane:

Choroidal neovascular membrane (CNVM) is one of the most severe causes of visual impairment in patients with uveitis. A uveitic CNVM or inflammatory CNVM usually occur adjacent to any post-inflammatory outer retinal or subretinal scar. CNVM secondary to uveitis can occur in both infectious and non-infectious uveitic entities.

Common causes inflammatory CNVM are listed below:

Majority of the inflammatory CNVMs are predominantly classical, and fundus fluorescein angiography is therefore excellent for diagnosis and monitoring.