Introduction

Pars planitis is a subtype of intermediate uveitis. The term ‘intermediate uveitis’ describes an intraocular inflammatory process, which is inflammation of the inner layers of the eye. In Pars Planitis, the pars plana is the is the primary site of inflammation which is a region located between the iris and choroid. 

There is usually bilateral involvement, meaning Pars Planitis affects both eyes. However, if the disease is asymmetrical, the less affected eye can show only a few cells in the vitreous.¹

The cause of Pars Planitis is unknown, however, it is thought to be autoimmune in nature. The most common presenting symptoms are floaters and blurred vision. Whilst some people with Pars Planitis may have minimal symptoms, the inflammatory process can lead to structural changes in the eye, and complications are not uncommon.

Eye immune privilege and pars planitis

The microenvironment in the eye is both immunosuppressive and anti-inflammatory in nature.² This immunosuppressive property of the cells and tissues in the eye is referred to as immune privilege. Immune privilege is essential as it prevents potential extensive damage that can be caused by infiltrating inflammatory cells that would otherwise lead to blindness. 

The eye expresses an extensive array of mechanisms through which innate and adaptive immune cells can be regulated. Your innate immune system is part of your body’s first-line defense. It has a rapid response to any pathogen that shouldn’t be in your body and includes the skin, mucus and stomach acid. Your adaptive immune system develops over time and in response to infection, it is a learned immunity. Because these responses are destructive, it is crucial that they be made only in response to molecules that are foreign to the host and not to the molecules of the host itself. This preserves the immune system from excessive inflammation and tissue damage.

In Pars Planitis, the eye's immune privilege is breached, allowing immune cells and their inflammatory products to invade and damage the eye's sensitive tissues.³

Key cellular players and immune cells involved

The cause of Pars Planitis remains unknown. The most widely accepted hypothesis is that Pars Planitis represents an autoimmune disorder of the eye. It is thought that the inflammation is most likely a reaction to an unknown endogenous antigen. Antigens are markers that tell your body that something is foreign. The exposure to this antigen leads to activation of the immune system. 

Overall, research suggests that Pars Planitis is primarily a T cell-driven disease. T cells are a type of white blood cell called lymphocytes and play an essential part in your immune system. T cells are the predominant cells present in the vitreous. CD4+ cells, also called T helper cells, send signals that tell other cells in your immune system how to coordinate an attack against invaders. Activated CD4+ cells are found in the blood and aqueous humor (fluid located in the eye) of patients with Pars Planitis.⁴

Taking it further, the specific CD4+ cells involved may be Th17 and Th1. It is thought that Th17 responses initiate inflammation, while Th1 cells maintain and reinforce it. As such, Th1 cells sustain local inflammation and tissue injury over time. Beyond Th1 and Th17, there is also a decrease in regulatory T cells, reinforcing the loss of immune regulation and promoting chronic inflammation. 

Cytokines and inflammatory mediators

Almost twenty five cytokines have been detected in the tears of healthy people. Cytokines help control inflammation and keep the normal physiological condition of the ocular surface.⁵ Studies of patients with Pars Planitis, have identified elevated levels of cytokines and immune activation markers in serum (a component of blood) and ocular fluid. 

In Pars Planitis, cytokine dysregulation reinforces the persistence of Th1- and Th17-driven inflammation in the eye (as discussed above). Additionally, IL-6 is one of the cytokines that seems to have a pathologic role in Pars Planitis. The main role of IL-6 is to be a pro-inflammatory cytokine. Therefore, IL-6 can amplify inflammatory responses. Patients with Pars Planitis seem to have very high levels of IL-6.⁶

Understanding how these cytokines and cellular interactions drive chronic inflammation is essential for designing targeted therapies that restore immune balance and preserve vision in patients with Pars Planitis.

Structural changes and clinical implications

Pars planitis usually affects both eyes. However, if it is asymmetrical, the less affected eye can show only a few cells in the vitreous. The most common symptoms of Pars Planitis are floaters and blurred vision. However, you may also experience eye pain, light sensitivity and redness. Sometimes, especially in children, the disease causes no symptoms and is discovered during routine eye exams. As symptoms are often mild, the disease can be diagnosed late, increasing the risk of long-term vision problems.¹

Changes in the front (anterior) part of the eye are usually mild. Small white deposits on the cornea, called keratic precipitates, are seen in about one-third to half of patients. Inflammation in the front chamber of the eye is common. In children, the iris can stick to the lens (posterior synechiae), and the outer edge of the cornea may show swelling with immune deposits (peripheral corneal endotheliopathy). Other front-eye changes, like calcium deposits on the cornea (band keratopathy), are also more common in children than adults.

In the back (posterior) part of the eye, Pars Planitis has more obvious signs. Doctors often see cells and haze in the vitreous, along with “snowballs” (clumps of inflammatory cells in the mid or lower vitreous) and “snowbanks” (inflammatory deposits along the pars plana, usually at the bottom of the eye). Blood vessels in the retina can also be inflamed. Swelling of the optic nerve (optic disc oedema) is also common. These changes show how the disease can seriously affect eye structure and vision if not recognised and treated early.

Complications

If inflammation is severe, there is a high risk of severe complications.¹ These include:

• Epiretinal membrane formation - this is scar tissue on the retina
• Cataracts - these cause your eye’s lens to become cloudy
• Cystoid macular edema - this is swelling of the macula, which is part of the retina
• Retinal vasculitis - this is inflammation in the blood vessels
• Retinal neovascularization - this is abnormal blood vessel growth
• Peripheral vitreous traction - this is when the vitreous shrinks and pulls away from the retina
• Vitreous haemorrhage - this is bleeding in the eye

Treatment 

Historically, there has been no consensus on treatment options for Pars Planitis, especially for those with minimal inflammation and relatively good visual acuity. However, current thought is that Pars Planitis is a severe disease which may cause ocular complications and thus needs aggressive treatment. It would seem that treating inflammation early and aggressively, rather than using a visual acuity threshold, which is how well you can see details from a distance, is more effective both in the short and long term. 

Treatment usually begins with steroids. Periocular (the tissue surrounding the eye) and intraocular (in the eye) injections are used, which avoid the negative side effects of systemic steroids. However, in severe Pars Planitis, oral prednisolone is started at a dose of 1-1.5mg per kilogram of body weight per day. This means that if you weigh 60kg, you may receive a dose of 60mg (or more) of prednisolone. For rapid action, intravenous pulse methylprednisolone 1 gram is also an option.¹

If you need longer immunosuppression, your doctor may advise on immunomodulatory therapy. These medications are referred to as steroid-sparing agents and include methotrexate, mycophenolate mofetil (MMF), azathioprine, and cyclosporine.

If you do not respond adequately to the steroid-sparing agents, your doctor may suggest biologics or anti-tumour necrosis factor agents (anti-TNF agent). Adalimumab has been approved for the treatment of noninfectious uveitis. However, anti-TNF agents may predispose to demyelination, which is damage to the protective cover of nerve cells. This is important because patients with Pars Planitis may be at a higher risk of developing multiple sclerosis.⁴ Therefore, extreme caution should be used and risk-benefit ratio evaluated. Interferon has also been used successfully in Pars Planitis, but adverse drug effects include depression and suicidal tendencies.

If the three treatment steps above are not effective and the inflammation progresses, pars plana vitrectomy (PPV) may be an option. This is a surgical procedure where the vitreous humor gel that fills the eye cavity is removed to provide better access to the retina. It is performed if you suffer from one of the complications mentioned above. 

Cataract surgery is another important intervention, but should only be performed once intraocular inflammation has been well controlled for at least three months with medical therapy.

Summary

Pars Planitis causes inflammation to the inner layers of the eye. Although it can be asymptomatic at first, it is a potentially blinding disease, due to complications as a result of excessive inflammation. 

The origin of Pars Planitis remains unknown. However, it is widely accepted that it is an autoimmune disorder of the eye triggered by T-cells, cytokines and inflammatory mediators. Treatment options are generally based on this immune-system involvement.

Ongoing research into Pars Planitis is enhancing the understanding of its clinical features, complications, and treatment options. Continued studies and clinical trials are essential for developing more effective therapies and improving outcomes in the management of this condition.