Intermediate uveitis can be associated with various conditions, including sarcoidosis, multiple sclerosis (MS), Lyme disease, peripheral toxocariasis, syphilis, tuberculosis, primary Sjögren syndrome, and infection with human T-cell lymphotropic virus type 1 (HTLV-1).
The term pars planitis refers to the subset of intermediate uveitis that is idiopathic with no associated infection or systemic disease. It is the most common form of intermediate uveitis, constituting approximately 85%–90% of cases. Previously also known as chronic cyclitis and peripheral uveitis, the condition most commonly affects persons aged 5–40 years. It has a bimodal distribution, concentrating in younger (5–15 years) and older (20–40 years) groups. No overall sex predilection is apparent. The pathogenesis of pars planitis is not well understood.
Approximately 80% of cases of pars planitis are bilateral, which can often be asymmetric in severity. In children, the initial presentation may consist of significant anterior chamber inflammation accompanied by redness, photophobia, and discomfort. The onset in teenagers and young adults may be more insidious, with the presenting complaint generally being floaters. Ocular manifestations include anterior chamber inflammatory cells, vitreous cells, snowballs (Fig 8-17), and pars plana exudates. Inferior peripheral retinal phlebitis with retinal venous sheathing is common. With long-standing inflammation, macular edema often develops; this condition becomes chronic and refractory in approximately 10% of patients and is the major cause of vision loss. Ischemia from retinal phlebitis, combined with angiogenic stimuli from intraocular inflammation, can lead to neovascularization along the inferior snowbank in up to 10% of cases. These neovascular complexes can result in vitreous hemorrhages, more common in children than adults; they also may contract, leading to peripheral tractional and rhegmatogenous retinal detachments. In rare cases, the complexes evolve into secondary peripheral retinal vasoproliferative tumors—vascular masses with exudative retinopathy and minimally dilated vessels—years after the initial diagnosis. Rhegmatogenous retinal detachments are rare but localized peripheral detachments (serous or tractional) that can occur in 4%–10% of patients with pars planitis. With chronicity, posterior synechiae and band keratopathy may also develop. Other possible causes of loss of vision include cataracts, epiretinal membrane, and vitreous opacification.
Figure 8-17 Pars planitis. A, Vitreous “snowball” opacity in the anterior, inferior retrolental vitreous. B, Same vitreous snowball opacity shown in retroillumination, revealing its location with respect to the lens as well as evidence of vitreous cellularity.
(Courtesy of Ramana S. Moorthy, MD/National Eye Institute.)
The differential diagnosis of intermediate uveitis includes syphilis, tuberculosis, Lyme uveitis, sarcoidosis, intermediate uveitis associated with MS, and toxocariasis. Syphilis should be checked in all uveitis patients, including those with intermediate uveitis. Measurement of Lyme antibody titers may be useful in regions where the disease is endemic, especially in patients with a history of tick bite or cutaneous and articular disease. Anterior and intermediate uveitis may occur in up to 20% of patients with MS. Sarcoidosis-associated uveitis presents as an intermediate disease in 7% of cases. A peripheral granuloma such as that seen in toxocariasis can mimic the unilateral pars plana snowbank in a child and should be ruled out. Serologic testing can be helpful in these cases.
Vitritis without other ocular findings can be suggestive of primary central nervous system (CNS) lymphoma. These patients are generally much older at presentation than patients with pars planitis, usually in their fifth or sixth decade of life or older.
Ancillary tests and histologic findings
The diagnosis of intermediate uveitis is made according to classic clinical findings. Laboratory workup to evaluate for other causes of intermediate uveitis, including sarcoidosis, Lyme disease in high-risk cases, and syphilis, is important. Measurement of serum angiotensin-converting enzyme (ACE) and Lyme antibody titers, chest imaging, and syphilis testing should be considered. Fluorescein angiography (FA) may show diffuse peripheral venous leakage, disc leakage, and macular edema. Ultrasound biomicroscopy may be used in the case of a small pupil or dense cataract to demonstrate peripheral exudates or membranes over the pars plana.
Histologic examination of eyes with pars planitis shows vitreous condensation and cellular infiltration in the vitreous base. The inflammatory cells consist mostly of macrophages, lymphocytes, and a few plasma cells. Pars planitis is also characterized by peripheral lymphocytic cuffing of venules and a loose fibrovascular membrane over the pars plana (Fig 8-18).
Figure 8-18 Fundus examination of a patient with undifferentiated intermediate uveitis (pars planitis). A, B, Note pars plana membrane inferiorly (arrows).
(Courtesy of H. Nida Sen, MD/National Eye Institute.)
The clinical course of pars planitis may be divided into 3 types. Approximately 10% of cases have a self-limiting, benign course; 30% have a smoldering course with remissions and exacerbations; and 60% have a prolonged course without exacerbations. Pars planitis can remain active for many years. In some cases, the disease “burns out” after a few years. If macular edema is treated until resolution and kept from returning by adequate control of inflammation, the long-term visual prognosis can be good, with nearly 75% of patients maintaining visual acuity of 20/40 or better after 10 years.
Therapy should be directed toward treating the underlying cause of the inflammation, and infectious etiologies should be ruled out prior to initiating therapy. If an underlying condition is not identified, as in pars planitis, or if therapy of an associated condition consists of nonspecific control of inflammation, as in sarcoidosis, anti-inflammatory therapy should be implemented.
Corticosteroids, oral or periocular, usually constitute the first line of therapy. Periocular depot corticosteroid injections of triamcinolone or methylprednisolone may be given via the posterior sub-Tenon (see Chapter 6) or orbital floor route. These can be repeated as frequently as every 3–4 weeks. In most cases, the inflammation responds and the macular edema improves; however, some cases prove recalcitrant and macular edema may recur. Patients, especially those with a history of glaucoma, must be carefully monitored for corticosteroid-induced IOP elevation. Other complications of periocular corticosteroids include aponeurotic ptosis, fat prolapse, enophthalmos, and, in rare instances, globe perforation. Cataract formation can occur with any form of corticosteroid therapy.
Intravitreal corticosteroid injections may be an alternative to periocular injections in refractory cases. These injections carry risks of sustained IOP elevation and glaucoma and very small risks of retinal detachment, vitreous hemorrhage, and endophthalmitis. Injections should be administered away from areas of snowbanking and areas with peripheral retinal pathology.
Other forms of local steroid injections, such as dexamethasone intravitreal implants, can also be considered. Local treatment with corticosteroid injections is a particularly appealing approach in unilateral cases.
Systemic corticosteroid therapy may also be used, especially in severe or bilateral cases. Patients may be treated with an initial dosage of 1 mg/kg/day, with gradual tapering every 1–2 weeks to dosages of less than 10 mg/day after 8 weeks of treatment.
As with all autoimmune uveitis, if corticosteroid therapy fails or long-term use of high doses of corticosteroids is needed to control the inflammation, immunomodulatory treatment is indicated. Systemic immunomodulatory drugs such as antimetabolites, T-cell inhibitors, biologic agents, and alkylating drugs can be considered. Several reports from the Systemic Immunosuppressive Therapy for Eye Diseases (SITE) cohort study indicated that cyclosporine, azathioprine, and mycophenolate mofetil were effective in achieving sustained control of inflammation in 70%–80% of patients with intermediate uveitis. The TNF inhibitor adalimumab is approved by the United States Food and Drug Administration for the treatment of uveitis, including intermediate uveitis. Because TNF inhibitors can exacerbate MS, it is important to consider an extensive workup for MS, including magnetic resonance imaging of the brain, before initiating this therapy. See Chapter 6 for more detailed information on IMT in uveitis.
Alternative therapies for pars planitis include peripheral ablation of the pars plana snowbank with cryotherapy and/or indirect laser photocoagulation to the peripheral retina. Cryotherapy is rarely used because of concerns about further inducing inflammation. Laser photocoagulation can be used in cases of retinal ischemia and neovascularization to prevent vitreous hemorrhage; it does not seem to increase the risk of rhegmatogenous retinal detachment. Intravitreal anti-VEGF treatment can also be used for retinal or choroidal neovascularization in pars planitis in otherwise quiet eyes.
Pars plana vitrectomy, with or without laser photocoagulation, can also be helpful in treating complications of pars planitis or in cases recalcitrant to IMT. In such cases, a perioperative increase in systemic immunosuppression and/or corticosteroids should be considered. Pars plana vitrectomy may be necessary to treat severe vision loss caused by vitreous hemorrhage or traction, retinal detachment, or epiretinal membrane. It can also be considered for cases with significant vitreous opacities despite adequate IMT. In cases involving epiretinal membrane or vitreomacular traction, separation of the posterior hyaloid membrane during vitrectomy may have a beneficial effect in reducing macular edema. Potential complications include retinal detachment, endophthalmitis, and cataract formation.
Complications of pars planitis include cataract, glaucoma, macular edema, retinal neovascularization, vitreous hemorrhage, retinoschisis, and tractional or rhegmatogenous retinal detachment. Cataracts occur in up to 60% of cases. Cataract surgery with IOL implantation may be complicated by smoldering low-grade inflammation; recurring opacification of the posterior capsule despite capsulotomy; recurrent retrolental membranes; and chronic macular edema, even in cases in which there is no active cellular inflammation. Combining pars plana vitrectomy with cataract extraction and IOL implantation may reduce the risk of these complications. Glaucoma—both angle-closure and open-angle—occurs in approximately 10% of patients with pars planitis. Macular edema may occur in 50% of patients with intermediate uveitis and is a hallmark of pars planitis. Neovascularization of the retina, disc, and peripheral snowbank has been reported. Occasionally, vitreous hemorrhage is the presenting sign of pars planitis, especially in children; it can be treated effectively with pars plana vitrectomy. Tractional and rhegmatogenous retinal detachments can occur in up to 10% of patients and may require scleral buckling, sometimes combined with vitrectomy. Risk factors for rhegmatogenous retinal detachment include severe inflammation, use of cryotherapy at the time of a vitrectomy, and neovascularization of the pars plana snowbank.
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Excerpted from BCSC 2020-2021 series: Section 9 - Uveitis and Ocular Inflammation. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.