SHERIDAN LAM and HOWARD H. TESSLER
Table Of Contents
PHAKIC PATIENTS WITH CYSTOID MACULAR EDEMA, RETINAL PERIPHLEBITIS, AND VITREOUS INFLAMMATION
IDIOPATHIC AGE-RELATED VITRITIS
SYSTEMIC CONDITIONS ASSOCIATED WITH INTERMEDIATE UVEITIS
|Intermediate uveitis is a chronic condition in which the signs of inflammation
are most pronounced in the vitreous. The term intermediate refers to the anatomic location of the inflammatory reaction, the middle
of the eye. The anterior segment, retina, and the optic disc may also
be involved. The amount of inflammation in other areas is less severe
than the vitreous reaction, which is the predominant feature in intermediate
In the past several terms have been coined to describe intermediate uveitis, such as cyclitis,1 chronic cyclitis,2 vitritis,3 peripheral uveitis,4,5 basal uveoretinitis,6 and pars planitis.7 In 1987, the term “intermediate uveitis” was adopted to bring uniformity to the description of this clinical entity.8
Intermediate uveitis has been reported to have an incidence of 0.3 per 100,000 and a prevalence of 1.4 per 100,000.9 Patients with intermediate uveitis typically report blurred vision and floaters. They seldom mention pain and photophobia, in contrast to patients with anterior uveitis. In intermediate uveitis, the anterior segment either is clear or shows low-grade inflammation. The conjunctiva is typically white and uninflamed. The cornea may show endothelial dusting due to deposition of fibrin and a few inflammatory cells. Typically, keratic precipitates are absent or minimal. The anterior chamber may be quiet or show mild flare with up to 2+ cells. The iris is not involved, although focal posterior synechiae form in some cases. The vitreous is the site where the inflammation is most heavily concentrated, and it shows varying amount of cells, fibrin, and cellular debris depending on the severity. In some cases (e.g., pars planitis), inflammatory exudates, called snowbanks, may form in the inferior vitreous base, over the peripheral retina, and the pars plana. The retina is often unremarkable, although retinal periphlebitis (i.e., sheathing), optic disc edema, and macular edema are present in some cases.
In most patients, intermediate uveitis is solely an ocular disorder. However, in a few patients, intermediate uveitis is part of a systemic disease. Systemic diseases that may present with intermediate uveitis include sarcoidosis, multiple sclerosis (MS), Lyme disease, Whipple's disease, HTLV infection, and intraocular lymphoma.9
|Pars planitis is the most common form of intermediate uveitis. The distinguishing
feature of pars planitis is the presence of inflammatory exudates
in the inferior vitreous base over the inferior peripheral retina, ora
serrata, and pars plana. The term “pars planitis” describes
the location of the inflammatory exudates that typify this clinical
About 4% to 15% patients referred for uveitis have pars planitis.10–17 Pars planitis usually affects children and young adults.18 It seldom develops before age 5 or after age 30. Most cases develop in the teens and early twenties. In most cases pars planitis enters remission before age 40. Some reports10,18 show no racial predilection, but others11,13,16 show that whites are affected more frequently than blacks. There is no predilection toward either sex.10,18 Pars planitis is bilateral about 71% to 75% of the time.4,13,19 Familial cases of pars planitis and intermediate uveitis have been reported.20–24
The onset of symptoms is very gradual in pars planitis. The most common symptoms of pars planitis are blurred vision and floaters. Symptoms may be present for months to years before the patient seeks medical attention. At times, patients with pars planitis are asymptomatic, and the diagnosis is made on a routine ophthalmic examination. Patients with pars planitis rarely report redness, pain, or photophobia.
Externally, the eyes of patients with pars planitis appear uninflamed. The conjunctiva and sclera are usually white without injection. The cornea is usually clear and appears uninvolved. In long-standing cases, band keratopathy may develop, most frequently in patients who developed pars planitis in childhood or their early teens.11,13 In some cases of pars planitis, small keratic precipitates and fibrin may be present on the corneal endothelium. Large keratic precipitates are not characteristic of pars planitis. The anterior chamber may be clear or show only mild cells and flare. The amount of inflammation in the anterior chamber is typically mild, rarely exceeding grade 2+ .25 The iris may be uninvolved or show only one or two localized posterior synechiae. Extensive iris synechiae, seclusion of pupil, and iris nodules are not typically seen in pars planitis. The lens may be clear or may appear cataractous. In pars planitis, posterior subcapsular cataract is most frequently seen, and it may be the result of ocular inflammation or the chronic use of corticosteroids.
In pars planitis, the inflammatory signs are greatest in the vitreous cavity. The vitreous gel is syneretic and shows varying amount of fibrin, cells, and strands. The hallmark of pars planitis is the presence of exudates in the inferior vitreous base (Fig. 1). In early stages these exudates may appear as discontinuous yellow-white clumps (fluffballs or snowballs). However, as the disease progresses, these exudates may increase in number and size until they coalesce to form a fluffy white exudate over the inferior peripheral retina and pars plana. Later, the exudate organizes into a smooth white fibrous-appearing band. This membrane has been termed a snowbank because of its resemblance to white fluffy snow. The term pars planitis is reserved for intermediate uveitis in which snowbank is present. The amount of vitreous inflammation is usually symmetric in both eyes. However, in some cases, a prominent snowbank may be present in one eye but only a few fluff balls in the other. Scleral indentation is often required to visualize the snowbank (Fig. 2).7,26
Retinal changes that can occur in pars planitis include perivascular sheathing of the retinal venules (periphlebitis), cystoid macular edema, and optic disc edema (Figs. 3 and 4). In cases of chronic cystoid macular edema, epiretinal membrane formation often occurs.4,13,27
FLUORESCEIN ANGIOGRAPHY AND VITREOUS FLUOROPHOTOMETRY
In pars planitis, fluorescein angiography shows diffuse leakage from the retinal venules and capillaries, without any predilection for the inferior retinal vasculature (Figs. 5 and 6).28 Similarly, vitreous fluorophotometry in patients with pars planitis also shows no predilection for vascular leakage in the inferior peripheral retina.29 These findings suggest that snowbank is most likely a sequela from ocular inflammation, that inferior peripheral retina periphery is not the source of inflammation in pars planitis, and that pars planitis is not a localized inflammatory response of the inferior retina.
The clinical course is marked by chronic low-grade inflammation, which may be punctuated by episodes of exacerbation. In a study of 100 patients, Smith and colleagues13 divided the clinical course of their patients into three categories. The first group (10% of the eyes) followed a benign self-limiting course of gradual clinical improvement without episodes of exacerbation. The second group (59% of the eyes) followed a smoldering, prolonged course without episodes of exacerbation. The third group (31% of the eyes) followed a smoldering and prolonged course with episodes of exacerbation. About 4% of their cases underwent spontaneous remission.
In pars planitis, the severity of the disease has no correlation to the duration of disease. Cases that are unilateral at first presentation may become bilateral later. Pars planitis is bilateral about 71% to 75% of the time.4,13,19 Often there is asymmetry in severity between eyes. In our experience, unilateral cases tend to have a milder course than bilateral cases. The presence of snowbank may indicate more severe and prolonged vitreous inflammation and often is associated with cystoid macular edema.30 In most of the patients, the clinical course becomes milder with time, and it usually enters remission between the patient's midthirties and early forties.
Few pathologic reports of pars planitis have been described. Most cases are long-standing and chronic. Early changes have not been reported.
Histologically, the snowbank is composed of glial elements, type VI collagen, and laminin.31 Extensive fibroglial proliferation and fibrous astrocyticlike cells have been seen in the vitreous base.32,33 These cells can synthesize basement membranes and produce large-diameter collagen fibrils.32,33 Fibrovascular tissue may be present in the snowbank and consists of well-differentiated capillaries that probably originate from the peripheral retina.33
The vitreous is usually collapsed and detached posteriorly from the retina. Multinucleated giant cells and epithelioid cells have been demonstrated in the vitreous snowballs.34 There is cellular proliferation from the retina and hyperplasia of the nonpigmented ciliary epithelium.34 The choroid usually does not show significant inflammation.31,34
Lymphocytic cuffing and mural infiltration of the retinal venules can be present, consistent with periphlebitis and phlebitis, respectively.33 The retinal arterioles are spared.33 These lymphocytes are mostly T-helper cells.31 Histologic changes consistent with clinical cystoid macular edema may be present in the fovea.33
ETIOLOGY AND PATHOGENESIS
The cause of pars planitis is unknown, and its pathogenesis remains unclear. As described in previous sections, inflammation in pars planitis is most prominent in the vitreous and seems to begin clinically in the inferior vitreous base, with formation of fluff balls during the early stages of disease. This suggests that the pathogenesis of pars planitis begins in the vitreous base. Snowbanks, resembling those in pars planitis, have been produced in monkeys35 receiving multiple intravitreal injections of hyaluronic acid and in rabbits36 receiving intravitreal injections of crystalline egg albumin. Further, a predominance of T-helper cells has been demonstrated in the snowbank glial tissue in one eye.31 These findings suggest that deposition of foreign antigens in the vitreous may lead to pars planitis.
The predilection for the inferior vitreous base to form snowbank is perhaps due to the gravitational settling of cells and debris from the inflamed vitreous in pars planitis. However, the formation of snowbank may also be due to an increased number of cells in the inferior vitreous.37
Elevated serum levels of IgD have been reported in patients with pars planitis.38 Humoral and cell-mediated immunity against the photoreceptor S-antigen have been demonstrated in some patients with pars planitis.39–41 The presence of retinal immunity may represent an epiphenomenon that occurs after the initial insult to the retina.39 A similar epiphenomenon has been observed in patients with diabetic retinopathy; they also show elevated serum levels of anti-S-antigen antibody after undergoing retinal photocoagulation.42 However, even if not primary, retinal autoimmunity may exacerbate the inflammation in pars planitis. Class II antigen has been demonstrated on the vascular endothelium in eyes with pars planitis, indicating that the vascular endothelium may also be part of the immunologic process.31
Electrophysiologic studies have shown B-wave abnormalities, suggesting a vitreoretinal disorder rather than a primary uveal disease in pars planitis.43
Linearly arranged keratic precipitates on the inferior corneal endothelium have been described in patients with pars planitis.44,45 Khoudadoust and coworkers44 proposed that these linear keratic precipitates are the results of autoimmune corneal endotheliopathy. However, Pivetti-Pezzi and Tamburi46 did not identify any cases of autoimmune corneal endotheliopathy in a retrospective study of 58 patients. It is doubtful that autoimmune corneal endotheliopathy and pars planitis are related disorders, and it is most likely that the keratic precipitates in pars planitis are from chronic anterior chamber reactions spilled over from the vitreous inflammation.47,48
Familial cases11,20–24,31,49 of pars planitis have been reported, suggesting a possible genetic predilection or a common environmental factor that may predispose certain individuals to develop pars planitis. Recently, human leukocyte antigen (HLA) DR15 has been associated with pars planitis.50,51 HLA-DR15 is also associated with MS, optic neuritis, and narcolepsy.50 HLA-DR15 may be a marker that predisposes some to develop pars planitis. Further, pars planitis may be a part of the disease spectrum associated with HLA-DR15.50 This is reminiscent of disorders related to HLA-B27, which include acute iridocyclitis, ankylosing spondylitis, Reiter's syndrome, ulcerative colitis, and psoriatic arthritis.
The most frequent complication in pars planitis is cystoid macular edema, which occurs in about 30% of cases.13,52 Cataracts have been reported in 5%52 to 42%13 of cases. With time, the percentage of pars planitis patients with visual loss due to macular disease tends to increase, whereas the percentage of pars planitis patients with visual loss due to cataracts and vitreous opacities tends to decrease.13 Cystoid macular edema and snowbank have been reported to be associated with a worse visual outcome.52
Retinal detachment, vitreous hemorrhage, optic disc swelling, and dragging of the optic disc vessels caused by contraction and neovascularization of cyclitic membranes occur in less than 10% of cases.13,52,53 Periphlebitis has been reported in about 21% of cases.52 Neovascularization of the optic disc53–55 and peripheral retina56 can also occur (Fig. 7). Coat's-like response has been reported in pars plantitis.57 Band keratopathy, glaucoma, and retinoschisis may develop as late sequelae in pars planitis.13
The diagnosis of pars planitis is based completely on history and clinical findings. Pars planitis is a chronic uveitis in which the most severely inflamed part of the eye is the vitreous. The vitreous should show the greatest concentration of inflammatory cells. Pars planitis is also characterized by the presence of vitreous fluff balls (Fig. 8) or a snowbank in the inferior vitreous base. Macular edema is another important feature in pars planitis, because pars planitis is one of the most common causes of cystoid macular edema in young adults. Pars planitis is a disease of the young and early middle-aged adults. The onset of pars planitis is usually in the late teens and early twenties; it rarely occurs after age 30.
The differential diagnosis includes chronic iridocyclitis and intermediate uveitis secondary to sarcoidosis. The relative paucity of anterior chamber cells and the presence of snowbank in pars planitis distinguish pars planitis from chronic iridocyclitis. Posterior synechiae tend to be larger and more numerous in chronic iridocyclitis than in pars planitis. However, children with pars planitis, younger than 12, frequently have an anterior chamber reaction with severe synechiae and band keratopathy, which are features more characteristic of chronic iridocyclitis than pars planitis. It is unclear whether these severe childhood cases represent true intermediate uveitis or severe chronic iridocyclitis with secondary cyclitic membrane formation.
Chronic iridocyclitis and intermediate uveitis secondary to sarcoidosis can resemble pars planitis. Patients with sarcoidosis tend to have more prominent sheathing of the retinal venules and larger mutton-fat-like keratic precipitates. Retinal, choroidal, and optic disc granulomas may form in patients with sarcoidosis. Opacities resembling snowballs or a string of pearls in the inferior peripheral vitreous are more characteristic of sarcoidosis than pars planitis.
Unilateral cases of pars planitis must be carefully evaluated for toxoplasmosis and toxocariasis.58 In both of these conditions, areas of inflammation are usually more focal than those in pars planitis. Old chorioretinal scars and vitreous cells emanating from focal areas of retinochoroiditis may be helpful in making the diagnosis of ocular toxoplasmosis. Peripheral retinal granuloma and dragging of the disc by fibrovascular tissue can occur in toxocariasis. A case of intermediate uveitis after cataract surgery has been found to be caused by chronic Propionibacterium acnes endophthalmitis.59
The laboratory evaluation of a patient with pars planitis includes a chest x-ray, analysis of serum lysozyme and angiotensin-converting enzyme levels, and serology for syphilis. When toxoplasmosis or toxocariasis is strongly suggested, appropriate laboratory tests should be ordered. In some patients, pars planitis and MS are present concomitantly. If MS is suspected, neurologic consultation is recommended, and checking for HLA-DR15 may be helpful. Pars planitis has also been reported in patients with Lyme disease.60,61 Infectious disease consultation and appropriate tests should be obtained, especially when there is a history of tick bite in endemic areas for Lyme disease. In the future, the polymerase chain reaction may be performed on aqueous humor or vitreous from eyes with pars planitis to identify possible infectious agents.
The mainstay of treatment of pars planitis is corticosteroids. The corticosteroid can be administered topically, orally, periocularly, or intravenously. Topical corticosteroids, such as prednisolone acetate or phosphate, are generally useful in treating the anterior chamber reaction that may be present in some pars planitis patients. Topical corticosteroids, however, are of little use to control the vitreous inflammation or the cystoid macular edema. Topical corticosteroids are generally used as an adjunct in treatment of pars planitis when there is a significant anterior chamber reaction. Cycloplegia may also be necessary to prevent posterior syne-chiae formation. Patients taking topical corticosteroids should be followed regularly, because prolonged use of topical corticosteroids may lead to elevated intraocular pressure and cataract formation.
We generally recommend the periocular injection of steroids into the posterior sub-Tenon's space in cases of significant vitreous reaction, cystoid macular edema, or retinal periphlebitis. Posterior sub-Tenon's injection provides the highest concentration of corticosteroids to the most inflamed part of the eye in pars planitis. We generally define visual acuity of 20/40 or less due to vitreous cells and floaters as significant, but obviously significant visual loss must be defined individually. A young pars planitis patient may have a visual acuity of 20/25 with significant clinical cystoid macular edema, whereas an older patient may have a visual acuity of 20/40 with no clinically significant macular edema. The loss of vision in the older patient may be due to permanent macular changes from previous macular edema. We frequently and periodically use fluorescein angiography to monitor the extent of macular edema. If both cataract and cystoid macular edema are present, laser interferometry or potential acuity testing may be useful to assess potentialmacular function. However, these tests frequentlyare overly optimistic in their prediction of im-provement.
In giving posterior sub-Tenon's injection, we follow the technique of Nozik,62 in which the corticosteroid is placed adjacent to the sclera posterior to the equator through the superotemporal conjunctival fornix (Fig. 9). We use a 25-gauge needle that is 5/8 long and attached to a tuberculin or 3-mL syringe. Under topical anesthesia, the patient sits in a chair with the back of the head against the headrest. The patient is instructed to look down in the direction of the elbow contralateral to the eye that is to receive the injection. The upper eyelid is lifted with the nondominant hand, and the dominant hand is used to direct the needle. The superotem-poral conjunctival fornix is penetrated with the needle bevel up. After the tip of the needle enters the fornix, the needle is rotated 180 degrees with bevel down. The needle is advanced along the sclera posteriorly slowly with a side-to-side sweeping motion until reaching the hub of the needle, and the injection is then given. When given properly, no medication should be visible anterior to the equator. Careful attention is given to the globe during the advancement of the needle; the movement of the globe should be far less than the sweeping motion of the needle. If there is an exact correspondence between the movements of the globe and the needle, the tip of the needle may be engaging the sclera, and the needle should be withdrawn slightly and then again carefully advanced. The goal is to have the corticosteroid delivered adjacent to the posterior sclera without penetrating the globe.
Freeman and associates63 have shown by ultrasound that the superotemporal placement technique results in more accurate placement of steroids near the macula. They demonstrated that through the superotemporal approach, the gravitational effect on the injected volume would pull the medication closer to the posterior pole, compared with the inferotemporal approach. In the latter approach, gravity should pull the medication away from the globe. The injection can be repeated every 2 to 3 weeks. The dose can vary from 0.5 mL of triamcinolone diacetate (Aristocort; 40 mg/mL) to 1 mL of methylprednisolone acetate (Depo-Medrol; 80 mg/mL). Triamcinolone diacetate is more soluble than triamcinolone acetonide (Kenalog). When there is concern about a pressure elevation, the diacetate might preferably be used because it dissipates after about 3 months, whereas the acetonide can cause problems for over 1 year. Methylprednisolone acetate is more apt to cause allergic reactions and fibrosis than the triamcinolone preparations. Posterior sub-Tenon's injection is an especially effective therapy in the treatment of cystoid macular edema in pars planitis, and it is also useful in reducing the cellular activity in the vitreous.64,65 The success rate in improving visual acuity with posterior sub-Tenon's injection is about 80% to 90%.64,65 Posterior sub-Tenon's injection is also useful in reducing the cellular activity in the vitreous in about 75% of cases.65
Close attention must be given to the intraocular pressure, which may become elevated after periocular corticosteroid injection. It is worth using topical corticosteroids four times a day for 2 weeks to eliminate injections in patients who are exquisite steroid-glaucoma responders. Lafranco and coworkers64 reported an incidence of 36% of elevated intraocular pressure greater than 8 mmHg in their series of 58 eyes receiving a total of 162 posterior sub-Tenon's injections. From our experience, when the injection is given properly, elevated intraocular pressure is seldom encountered with posterior sub-Tenon's injection of corticosteroids. With periocular injections, other risks include ocular perforation, worsening cataract, and superior eyelid ptosis.64,65
We use oral corticosteroids when there is exacerbation of inflammation in both eyes, when the patient cannot receive periocular injections of corticosteroids, or when periocular injections fail to work. Sometimes oral corticosteroids are used as an adjunct to the periocular injection, especially in severe or recalcitrant cases. We generally prefer using periocular corticosteroid injections to oral corticosteroids for several reasons. Periocular injection delivers a much higher concentration of corticosteroids to the eye than oral corticosteroids. There are fewer serious side effects with periocular corticosteroids. With oral corticosteroids, side effects include elevation of the serum glucose level, elevation of blood pressure, loss of bone density, weight gain, water retention, increased skin fragility, easy bruisability, and psychological changes. We generally do not recommend the prolonged use of oral corticosteroids in treating pars planitis.
Intravenous pulse corticosteroids are seldom used to treat pars planitis. Although intravenous pulse therapy with methylprednisolone has been used in the treatment of pars plantitis,66 we have never used intravenous corticosteroids as a first-line treatment of pars planitis, except in cases in which the patient also has MS and coincident optic neuritis.
Carbonic anhydrase inhibitors can be beneficial in the treatment of cystoid macular edema in pars planitis. Carbonic anhydrase inhibitors may be given orally or topically. Cox and coworkers67 have shown that oral acetazolamide and dichlorphen-amide are effective in treating cystoid macular edema in pars planitis. However, Whitcup and colleagues68 later reported no improvement in visual acuity in uveitis patients treated with acetazolamide for cystoid macular edema. Topical carbonic anhydrase inhibitors have not been tried in cystoid macular edema in pars planitis. One of the topical carbonic anhydrase inhibitors, dorzolamide, has been reported to be effective in improving the macular edema on the fluorescein angiogram in patients with retinitis pigmentosa.69 However, dorzolamide did not improve the visual acuity in these patients. The main disadvantage of carbonic anhydrase inhibitors is that macular edema frequently returns after cessation of the therapy. Carbonic anhydrase inhibitors may be useful in patients with very mild cystoid macular edema.
Cryotherapy of the inferior snowbank has been advocated.70–72 Some patients have entered remission and have had improved visual acuity after cryotherapy. However, cryotherapy usually is a temporizing measure, and the snowbanks usually return 3 to 6 months after treatment.70 Recently, Pulido and coworkers73 reported that peripheral retinal laser photocoagulation was effective in pars planitis in decreasing the use of corticosteroids, decreasing the vitreous inflammation, decreasing the neovascularization at the vitreous base, and improving cystoid macular edema. It seems reasonable to consider peripheral retinal laser photocoagulation in pars planitis patients who are not responding well to corticosteroids or who are not tolerating the side effects of corticosteroids.
Vitrectomy may be of benefit for cases of cystoid macular edema or persistent intraocular inflammation that fail to respond to corticosteroids.74,75 After a 3- to 4-month course of unsuccessful corticosteroid therapy, we might consider vitrectomy. From our experience, vitrectomy may be beneficial in treating recalcitrant vitreous inflammation and cystoid macular edema. However, the cystoid macular edema may take months to resolve after vitrectomy and often requires intensive corticosteroid therapy after surgery. Vitrectomy is also effective in removing persistent vitreous hemorrhage and vitreous debris. Epiretinal membrane peel can also be accomplished through vitrectomy.76 Although vitrectomy is useful, it has the potential complications of endophthalmitis, retinal tears, and retinal detachment, and often visually significant cataract develops after vitrectomy in patients with pars planitis.
In some patients with pars planitis, a favorable therapeutic response has been noted with the use of immunosuppressive agents77 such as chlorambucil,78,79 azathioprine,80,81 cyclophosphamide,82,83 and methotrexate.84,85 However, there is no clear evidence that traditional immunosuppressives hold any value when corticosteroids are ineffective. Steroid-sparing agents such as methotrexate and azathioprine are frequently substituted for corticosteroids in patients who require more than 3 to 6 months of high-dose (over 10 mg/day) prednisone. The long-term side effects of methotrexate and/or azathioprine may be less than those of corticosteroids. Immunosuppressive agents may be used cautiously in patients who have failed to respond to corticosteroid therapy and vitrectomy. Immunosuppressives in these patients, however, may need to be maintained indefinitely to keep the intraocular inflammation under control. The side effects of immunosuppressives are considerable, including bone marrow suppression, infertility, and organ toxicities. We recommend that if the ophthalmologist is unfamiliar with these drugs, an internist be consulted in monitoring the patient.
Cyclosporine has been reported to decrease the intraocular inflammation and improve macular edema in uveitis patients in whom corticosteroid therapy previously failed.86–89 However, in these patients, long-term use of cyclosporine is required. Nephrotoxicity occurs in about 50% to 75% of these patients, and the serum creatinine level must be monitored closely.89,90 Other side effects include gingival hyperplasia and hirsutism.89 We recommend the use of cyclosporine and other immunosuppressives only when the patient has failed to respond to corticosteroid therapy. Usually cyclosporine is used as a steroid-sparing agent to reduce the need for high-dose systemic corticosteroids.
Cataract surgery in pars planitis patients can be helpful. However, much attention must be paid to the amount of intraocular inflammation. We generally would not recommend cataract surgery unless the eye has been clear of active inflammation for at least 3 months. Exacerbation of intraocular inflammation, elevated intraocular pressure, and development of cystoid macular edema must be monitored closely after surgery. Fogla and coworkers91 reported a rate of 94% of visual improvement after cataract surgery in 52 eyes with intermediate uveitis. Michaelson and associates92 reported enveloping dense fibrous membranes (cocoons) in some patients with pars planitis and intraocular lenses. Some of these intraocular lenses had to be removed due to the density of the membranes and failure of the Yag laser to clear them. Low-grade postoperative inflammation can cause this problem, and patients must be monitored frequently for the first 3 to 6 months. Opacification of the posterior capsule tends to develop early and frequently in these patients, and laser capsulotomy may be required. We would proceed with laser capsulotomy only if the eye were uninflamed and cystoid macular edema were controlled.
|Clinical signs and symptoms of chronic cyclitis are similar to those of
pars planitis. The main difference between chronic cyclitis and pars
planitis is the absence of pars plana exudate in chronic cyclitis.93 Other clinical signs, such as lack of conjunctival injection, minimal
anterior chamber reaction, posterior subcapsular cataract, vitreous cells, cystoid
macular edema, retinal periphlebitis, and mild disc swelling, can
be present in both pars planitis and chronic cyclitis.|
Like pars planitis, chronic cyclitis appears to be most prevalent in young adults and is usually bilateral. Some patients have pars planitis in one eye and chronic cyclitis in the contralateral eye. Some patients with chronic cyclitis may go on to develop pars plana exudates. Pars planitis exudate has been associated with more severe vitreous reaction and a higher incidence of cystoid macular edema.30 Henderly and coworkers30 distinguished cases of intermediate uveitis by the presence or absence of snowbanks and found little difference in prognosis. It could be that chronic cyclitis and pars planitis represent different manifestations of the same disease. Chronic cyclitis may represent an earlier stage or a milder form, whereas pars planitis may represent a later stage or a more severe form of the same disease.
The workup and treatment are identical between chronic iridocyclitis and pars planitis.
|PHAKIC PATIENTS WITH CYSTOID MACULAR EDEMA, RETINAL PERIPHLEBITIS, AND VITREOUS INFLAMMATION|
|In 1998, Park and associates94 reported a group of 19 patients with intermediate uveitis, with 15 of them being women and 35 eyes affected. The average age was 38. The distinctive clinical features of these patients included bilaterality in most patients, female predominance, cystoid macular edema, retinal periphlebitis, vitreous inflammation, absence of snowbanks, no associated systemic disorders, and no specific HLA association. It remains to be seen whether other similar cases will be reported in the future. The significance of this report is that HLA association is used in the description and classification of intermediate uveitis.|
|IDIOPATHIC AGE-RELATED VITRITIS|
|Age-related (senile) vitritis refers to patients over the age of 50 or 60 who present with an intermediate uveitis of unknown etiology. Many of these patients develop severe cystoid macular edema poorly responsive to conventional therapy of periocular or oral corticosteroids. This is a diagnosis of exclusion, and entities such as sarcoidosis and intraocular lymphoma must be considered.95|
|SYSTEMIC CONDITIONS ASSOCIATED WITH INTERMEDIATE UVEITIS|
Sarcoidosis is a systemic disorder that causes chronic inflammation in the eye. The most common form of uveitis with sarcoidosis is chronic granulomatous iridocyclitis. Although less common, intermediate uveitis with or without snowbanks can also occur in ocular sarcoidosis. The prevalence of sarcoidosis in patients with intermediate uveitis has been reported to be 2% to 10%.96 The treatment of intermediate uveitis associated with sarcoidosis is identical to that of pars planitis and chronic cyclitis.
Multiple sclerosis is a disorder of the central nervous system in which intermediate uveitis can also occur. The prevalence of MS in patients with intermediate uveitis at the University of Illinois Eye Center is 5.8% (Moy and Tessler, unpublished data). Others have reported a prevalence rate of 1% to 16%.18,54,96 Because the prevalence rate of intermediate uveitis in the general population has been reported to be 1.4 per 100,000,9 these data indicate that there is a definite association between MS and intermediate uveitis. As in pars planitis and chronic cyclitis, MS patients with intermediate uveitis have the identical clinical features, such as snowbanks, vitreous cellular debris, peripheral retinal vascular sheathing, and cystoid macular edema.97–102 Chronic granulomatous iridocyclitis can also occur in MS patients.92,103 The treatment of intermediate uveitis associated with MS is identical to that for pars planitis, with the exception that intravenous corticosteroid therapy is indicated if there is concomitant optic neuritis.
Intraocular lymphoma (i.e., reticulum cell sarcoma) may masquerade as intermediate uveitis. Eyes with intraocular lymphoma are typically uninflamed. The anterior chamber is quiet or shows mild cellular reaction. Posterior synechiae are typically absent. The vitreous cells in intraocular lymphoma may cause vitreous haze and give the appearance of chronic vitritis. The retina can show perivascular sheathing and subretinal masses. Focal chorioretinal lesions can also be present and may resemble those seen in birdshot (vitiligenous) retinocho-roidopathy104 or fundus flavimaculatus.105 The lymphoma cells may settle in the peripheral inferior vitreous base and give rise to snowbanklike deposits. Intraocular lymphoma should be suspected particularly in elderly patients with intermediate uveitis that does not respond to corticosteroid therapy. The diagnosis of intraocular lymphoma is usually established through vitreous biopsy, but in some cases chorioretinal biopsy is necessary. An interleukin 10 to interleukin 6 ratio greater than 1.0 in the vitreous or the cerebrospinal fluid is suggestive of primary intraocular lymphoma, but this is not always the case.106 Rearrangement heterogeneity of the IgH gene in the tumor cells, which can be detected through polymerase chain reaction, also supports the diagnosis of ocular lymphoma.106 The workup of patients with intraocular lymphoma is done with oncology consultation. Computed tomography, magnetic resonance imaging, and a lumbar puncture may be necessary to search for extraocular sites of lymphoma. In intraocular lymphomas, 53% of cases are of B-cell origin and 21% are of T-cell origin.107 The treatment of intraocular lymphoma often includes chemotherapy or radiation or both. AIDS can also lead to intraocular lymphoma, and it should also be considered in the workup of intraocular lymphoma.108,109
Whipple's disease is a systemic entity that predominantly affects men in the fourth to seventh decade of life.110 The gastrointestinal system is the primary site of infection, but the eye and the central nervous system can also be involved.111 It is caused by the PAS-positive diastase-resistant bacillus Tropherma whippelii. Whipple's disease can involve the eye after the systemic diagnosis is made but at times can present with ocular symptoms first. It has been reported to cause an intermediate uveitis with retinal periphlebitis and hemorrhages as well as granulomatous iridocyclitis.112
Diagnosis can be made by vitrectomy and the identification of the organism. PAS-positive material will be in macrophages. Electron microscopy can identify the organism, and the polymerase chain reaction can also be used. Recently the organism has been cultured.113
It is important to diagnose Whipple's disease because it responds to antibiotics. Antibiotic combinations including doxycycline, rifampin, and ceftriaxone have been used.
6. Bec P, Arne JL, Philippot V et al: L'uveo-retinite basale (uveite pérphérique, cyclite posterieure chronique, pars planitie, vitrite, hyalo-rétinte) et les autres inflammation de la périphérie rétinienne. Arch Ophthalmol (Paris) 37:169, 1977
36. Zimmerman LE, Silverstein AM: Experimental ocular hypersensitivity: Histopathologic changes observed in rabbits receiving a single injection of antigen into the vitreous. Am J Ophthalmol 48:447, 1959
64. Lafranco DM, Tran VT, Guex-Crosier Y, Herbert CP: Posterior sub-Tenon's steroid injections for the treatment of posterior ocular inflammation: Indications, efficacy and side effects. Graefes Arch Clin Exp Ophthalmol 237:289, 1999
86. Nussenblatt RB, Palestine AG, Chan CC: Cyclosporin A therapy in the treatment of intraocular inflammatory disease resistant to systemic corticosteroids and cytotoxic agents. Am J Ophthalmol 96:275, 1983