Pars Planitis

Etiology

Etiology of pars planitis remains unknown. The most widely accepted hypothesis is that pars planitis represents an autoimmune disorder of the eye. Exposure to an antigen initiates it. The nature of the antigen is not yet known, and this antigen exposure leads to activation of the immune system. The immunogenetic association has been suggested by studies citing association of HLA-B51, HLA-DR2, HLA-DR15,[3] and HLA-DRB1*0802 haplotypes with pars planitis.[2]

Epidemiology

In a prospective epidemiology study of 215 uveitis patients, Vadot et al.[4] found an incidence of 1.4 per 100,000 in France and a prevalence of 5.9 per 100,000. In the United States, Gritz and Wong found an incidence of 1.5 per 100,000 and a prevalence of 4 per 100,000.[5] The disease primarily affects children and adults through the fourth decade. Seventy percent to 90% of cases are bilateral, though most of the time one eye is more symptomatic. There is no sex or race predisposition.

Pathophysiology

The pathogenesis of pars planitis is not completely understood. Pars plana exudates are composed of a loose fibrovascular layer containing occasional fibrocyte-like cells and scattered mononuclear cells.

T cells are the predominant cells present in the vitreous; their percentage varies from 11% to 95%. CD4+ T cells account for 5% to 75% of all the T cells. CD4+ T cells that express CD69,[6] an activation marker, are found in aqueous humor and the blood of the patients with pars planitis. The role of CD8+T cells and B cells in the pathogenesis of pars planitis is not clear. Levels of IL-6 are elevated when compared to other cytokines: IL-1, TNF-alpha, and IL-2.[7] After T cells, macrophages are the second most common cells present.

History and Physical

Patients with pars planitis present with minimal symptoms, for example, floaters or blurry vision. In most cases, there is the absence of photophobia and pain. Occasionally patients may present with sudden loss of vision due to retinal detachment or acute vitreous hemorrhage.

Clinical signs of anterior segment inflammation may be present, mild anterior chamber cells. A characteristic sign of pars planitis is vitreous cell infiltration, ranging from 1+ to 4+. Sometimes the cellular infiltration is so dense that it may obscure the view of the retina. Snowballs, are the yellowish, white vitreal aggregate hallmark and are found in the inferior periphery. Peripheral vasculitis may be seen in 10% to 32% of patients. This may present as venous sheathing which may lead to occlusion and occasionally retinal neovascularization. Cystoid macular edema may be present and is the usual cause of visual decline. There may be complicated cataract (posterior subcapsular cataract).

During the acute phase, white exudates are present, in the later stage, there is collagen production which results in snowbank formation. Snowbanks are mostly located inferiorly, but occasionally they may encompass the entire peripheral retina. 

Evaluation

Diagnosis of pars planitis is based on clinical findings. The presence of more vitreous cells than anterior chamber cells, vitreous snowballs, and the presence of pars plana exudates suggest pars planitis. There may be peripheral vascular sheathing and/or cystoid macular edema/ epiretinal membrane.

Clinical evaluation includes the measurement of visual acuity, intraocular pressure, and slit lamp examination. All patient with pars planitis should be evaluated with a thorough peripheral retinal examination with scleral depression. Chest x-ray or CECT (contrast-enhanced computed tomography) scan of the chest may be done to evaluate for the presence of sarcoidosis and tuberculosis. Serum angiotensin-converting enzyme (ACE) level may be checked. This may be elevated in patients with sarcoidosis.

Other investigations may include complete blood count, erythrocyte sedimentation rate (ESR), venereal disease research laboratory (VDRL) or rapid plasma reagin test, Mantoux,  and serology for human immunodeficiency virus (HIV).

In cases with extensive vitritis, infective causes including toxoplasmosis, acute retinal necrosis, and endophthalmitis must be ruled out before starting steroid therapy.

In very elderly patients with vitritis/vitreous haze and no cystoid macular edema, primary intraocular lymphoma should be ruled out.

Fluorescein angiography will show the extent of vasculitis and show areas of retinal nonperfusion and neovascularization. Optical coherence tomography will show the presence of macular edema, epiretinal membrane, and vitreoretinal traction.

In occasional cases with severe vitreal infiltration, when posterior uveitis, retinitis, endophthalmitis, or tumors are difficult to exclude, a diagnostic vitrectomy may be performed.

Treatment / Management

Treatment decisions are based on the extent of pars plana infiltration, the extent of vasculitis, and coexisting macular edema.

Original Kaplan's four-step ladder approach[2] for pars planitis consisted of:

1. Regional corticosteroid injections followed by oral prednisolone if the regional/periocular steroid is not effective
2. Cryotherapy or laser photocoagulation of peripheral retina.
3. Pars plana vitrectomy (PPV)
4. If all 3 previous options fail, immunosuppressive steroid-sparing agents were considered. 

However, in current practice, most of the uveitis-specialists use periocular (subtenon)/intraocular and/or oral steroids for pars planitis. Subtenon triamcinolone or intravitreal triamcinolone or other steroid implants (Ozurdex) are usually considered in asymmetrically severe intermediate uveitis with cystoid macular edema. In bilateral cases, one eye may be followed by another periocular or intravitreal steroid which avoids the systemic side effects of steroids. The risk of glaucoma and cataract must be explained to the patient before any intervention with periocular or intraocular steroid.  Topical steroid drop is started only if there are significant anterior chamber cells,

In bilateral cases, unilateral cases not responding to periocular or intraocular steroid, and severe pars planitis, oral prednisolone is started in a dose of 1-1.5mg/kg/day.[2] For rapid action, intravenous pulse methylprednisolone 1g is an option.

Immunomodulatory therapy should be considered as a second step in patients who need longer immunosuppression. Commonly used steroid-sparing immunomodulatory agents include methotrexate, mycophenolate mofetil (MMF), azathioprine, and cyclosporine. 

Anti-tumor necrosis factor agents or biologicals are used as the third step in patients nor responding to conventional immunomodulatory therapy. Adalimumab is the biologic response modifier a tumor necrosis factor (TNF) inhibitor which has been approved for the treatment of noninfectious uveitis. Anti-TNF agents may predispose to demyelination and patients with pars planitis may be at a higher risk of developing multiple sclerosis irrespective of therapy. Thus extreme caution should be used and risk-benefit ratio evaluated before starting a pars planitis patient on an anti-TNF agent. Interferon has also been used successfully in pars planitis, but adverse drug effects include depression and suicidal tendencies.

PPV comprises the 4th step[2] and indications for PPV in pars planitis include vitreous hemorrhage, retinal detachment, severe vitreous opacification, epiretinal membrane (ERM),  and vitreomacular traction (VMT). PPV has the advantage of the removal of the load of inflammatory cytokines in the vitreous and provides an opportunity to remove the mechanical factors causing macular edema including VMT and ERM. The rare risk of PPV includes retinal detachment and recurrence of pars planitis.

Peripheral scatter laser photocoagulation is effective in the treatment of peripheral neovascularization associated with pars planitis. Cryotherapy is another option for peripheral neovascularization, but is painful and may predispose to the development of retinal detachment.

Cataract surgery: Cataract formation is one of the most common complications of pars planitis. Cataract extraction is safe if the intraocular inflammation is controlled with corticosteroids or immunosuppressives for a minimum of three months before surgery.

Differential Diagnosis

• Acute complications of sarcoidosis

• Cat scratch disease 

• Hepatitis C

• HLA-B27 syndromes 

• Inflammatory bowel disease

• Interstitial keratitis 

• Lyme disease

• Multiple sclerosis

• Toxocariasis

• Toxoplasmosis

Complications

Although pars planitis is one of the benign forms of uveitis, severe complications secondary to chronic inflammation may occur.

An important ocular complication is epiretinal membrane formation with a reported incidence of 7% to 36%, the mean duration between onset of pars planitis and epiretinal membrane formation has been reported to be 6.5 to 7.9 years. Cataracts are reported to occur in 14% to 30% of pars planitis cases They may occur as a result of the disease or as a result of treatment with corticosteroids, and it is difficult to distinguish between the two causes. A posterior subcapsular cataract is the most commonly diagnosed cataract. Cystoid macular edema is described as the major cause of vision loss. Other complications include retinal vasculitis, retinal neovascularization, peripheral vitreous traction, and vitreous hemorrhage.

 In a study, the complications of pars planitis 'included macular edema (47.7%), vitreous opacities (38.6%), papillitis (38.6%), vasculitis (36.4%), and cataract (20.5%)'.[8]