Pars Plana Vitrectomy for Cystoid Macular Edema Secondary to Sarcoid Uveitis

Junichi Kiryu, MD,1 Mihori Kita, MD,2 Teruyo Tanabe, MD,1 Kenji Yamashiro, MD,1 Noriko Miyamoto, MD,1 Yoshiaki Ieki, MD1
Objective: To examine the results of pars plana vitrectomy for cystoid macular edema secondary to sarcoid uveitis resistant to medical treatment. Design: Retrospective, interventional, noncomparative case series. Subjects: Fourteen consecutive subjects (18 eyes) with cystoid macular edema associated with sarcoid uveitis resistant to medical treatment. Intervention: All eyes underwent pars plana vitrectomy. Nine eyes also underwent peeling of the epiretinal membrane or removal of the posterior vitreous cortex. Main Outcome Measures: Status of macular edema, visual acuity, and complications. Results: Ten eyes (56%) improved 2 or more lines of Snellen visual acuity within 12 months. Six eyes (33%) remained unchanged, within a line of preoperative Snellen visual acuity, and two eyes (11%) worsened by 2 or more lines of Snellen visual acuity. Slit-lamp biomicroscopy showed that cystoid macular edema had resolved in 14 eyes (78%) within 9 months postoperatively. One eye (6%) had minimal edema, whereas three eyes (17%) remained unchanged biomicroscopically at the nal visit. Postoperative complications included cataract formation, glaucoma, optic nerve atrophy, epiretinal membrane formation, and tractional retinal detachment. No severe postoperative inammation was noted. Conclusions: Pars plana vitrectomy seems to have a benecial effect on cystoid macular edema caused by sarcoidosis resistant to medical treatment. Ophthalmology 2001;108:1140 1144 2001 by the American Academy of Ophthalmology. Sarcoidosis consists of a multifocal granulomatous inammation of unknown origin, but frequent sites of involvement include the lungs, skin, and eyes. The prevalence of ocular involvement in sarcoidosis ranges between 25% and 50%1 4 and reportedly accounts for 7% of all cases of uveitis.5 Sarcoid uveitis is reportedly the most common form of uveitis in Japan.6 Macular edema is a major cause of severe visual loss in patients with posterior uveitis, including that caused by sarcoidosis. Cystoid macular edema is known to be related to poor visual acuity at the initial examination of 60% of eyes with pars planitis.7 Corticosteroids, either systemic or periocular, are the primary treatment of cystoid macular edema caused by intraocular inammation, although their side effects often preclude long term use. The role of acetazolamide has not been determined.8 11 Evidence suggests that vitrectomy plays a role in the treatment of macular edema that has previously shown a
Originally received: May 26, 2000. Accepted: January 22, 2001. Manuscript no. 200310. 1 Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan. 2 Department of Ophthalmology, Ohtsu Red Cross Hospital, Ohtsu, Japan. Supported by a grant-in-aid for Scientic Research from the Ministry of Education, Science, and Culture, Japan. Reprint requests to Junichi Kiryu, MD, Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Sakyoku, Kyoto 606-8507, Japan.

poor response to medical therapy.1214 It has been reported that vitrectomy reduces macular edema in eyes with pars planitis15 and other forms of posterior segment ocular inammation.16 In this study, we evaluated the role of pars plana vitrectomy for cystoid macular edema secondary to sarcoid uveitis resistant to medical treatment.

Patients and Methods

We reviewed the records of 14 consecutive subjects (18 eyes) with cystoid macular edema secondary to sarcoid uveitis who underwent pars plana vitrectomy at the Kyoto University Hospital from 1995 to 1998 (Table 1). Eleven patients had an established diagnosis of sarcoidosis on the basis of clinical ndings and histologic conrmation by biopsy. Three patients, not subjected to biopsy, were diagnosed as having sarcoidosis by at least two of the following ndings:17 (1) negative puried protein derivative (PPD) test result; (2) positive serologic test result, including elevated serum angiotensin-converting enzyme, lysozyme, or gamma globulin; or (3) radiographic testing, including bilateral hilar adenopathy on chest radiography or gallium scan ndings consistent with sarcoidosis. Other requirements for inclusion were (1) visual acuity of less than 20/30 caused by cystoid macular edema as determined by slit-lamp biomicroscopy and uorescein angiography; (2) no visually signicant media opacities; (3) no improvement after medical treatment, including corticosteroids and acetazolamide (Table 2); and (4) follow-up for a minimum of 12 months postoperatively. All patients gave their informed consent for the surgery. Postoperative follow-up ranged from 12 to 58 months (mean, 25 months). The 14 patients consisted of 3 men and 11 women;
ISSN 0161-6420/01/$see front matter PII S0161-6420(01)00558-9

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Table 1. Patient Data

Duration of Visual Acuity Cystoid Cystoid Macular FollowMacular Patient Age Edema up PrePostEdema No. Gender (yr) (mos) (mos) operative operative Resolution 1 1 2 3 3 4 5 6 7 (OD) 7 (OS) 8 9 10 11 12 (OD) 12 (OS) 13 14 (OD) (OS) (OD) (OS) F F F F F F F F F F M M F F F F F M 66 65 73 66 67 62 66 54 53 53 59 32 72 56 57 58 58 60 17 8 12 8 12 5 5 13 29 29 8 12 11 9 9 13 18 8 18 27 12 18 14 14 33 29 30 30 35 58 26 18 14 12 14 54 20/100 20/30 20/200 20/70 3/200 20/30 20/200 20/40 20/70 20/50 20/200 20/50 20/200 20/30 3/200 20/200 20/70 20/200 20/25 20/20 20/100 20/70 20/100 20/50 20/20 20/40 20/25 20/70 20/30 20/25 20/100 20/40 20/400 20/40 20/30 20/200 Yes Yes Yes Yes No No Yes Yes Yes No Yes Yes Yes No Yes Yes Yes Yes

Combined Surgery Yes Yes Pseudophakia Pseudophakia Pseudophakia Yes No No No No No No Yes No Yes Yes Yes Yes

Posterior Vitreous Detachment Yes Yes Yes No No ERM Yes ERM Yes Yes ERM Yes ERM Yes No No ERM Yes

Treatment Preoperative TS/SY TS/SY TS/SY TS/AC TS/AC TS/SY TS/SY TS/AC TS/SY TS/SY TS/SY TS/SY TS/SY/AC TS/SY/AC TS/SY TS/SY TS/SY/AC TS/SY Postoperative TS TS TS TS TS TS/ST/AC TS TS/AC TS/SY/AC TS/SY/AC TS TS/SY TS TS/SY/AC TS TS TS/SY/AC TS

Postoperative Complications None None None None None GLA GLA, CAT ERM, CAT CAT CAT GLA, CAT CAT None CAT RD None GLA None

Subsequent Surgery None None None None None None PEA IOL None PEA IOL PEA IOL PEA IOL PEA IOL None PEA IOL VIT None None None

AC acetazolamide; CAT cataract; ERM epiretinal membrane; GLA glaucoma; OD right eye; OS left eye; PEA IOL phacoemulsication aspiration intraocular lens implantation; RD Retinal detachment; SY systemic steroid; TS topical steroid; VIT vitrectomy.

ages ranged from 32 to 73 years (mean, 60 years). Preoperative follow-up after presentation with cystoid macular edema ranged from 5 to 29 months (mean, 12.5 months). Fifteen eyes were phakic, and 3 eyes were pseudophakic. No visually signicant media opacities were noted, although some eyes had vitreous cells and debris, as well as mild cataract. Surgery was performed with the patients under local anesthesia with a sub-Tenons peribulbar injection of 3 ml 2% lidocaine.18

Pars plana vitrectomy was performed with standard three-port access to the vitreous cavity with sclerotomies 3.5 mm posterior to the limbus. A combined lensectomy vitrectomy procedure was performed in six patients (eight eyes), who were between 57 and 72 years of age. A 3.5- to 5-mm sclerocorneal incision was made at the limbus, after which phacoemulsication was performed, and a posterior chamber intraocular lens was placed in the capsular bag. The posterior vitreous was detached from the retina with an

Table 2. Steroid Therapy

Patient No. 1 1 2 3 3 4 5 6 7 7 8 9 10 11 12 12 13 14 (OD) (OS) (OD) (OS) Topical Steroid Betamethasone sodium phosphate 0.1% every 4 hrs Betamethasone sodium phosphate 0.1% every 4 hrs Betamethasone sodium phosphate 0.1% every 6 hrs Betamethasone sodium phosphate 0.1% every 3 hrs Betamethasone sodium phosphate 0.1% every 3 hrs Fluorometholone alcohol 0.1% every 3 hrs 5 mos Betamethasone sodium phosphate 0.1% every 3 hrs Betamethasone sodium phosphate 0.1% every 3 hrs Betamethasone sodium phosphate 0.1% every 4 hrs Betamethasone sodium phosphate 0.1% every 4 hrs Fluorometholone alcohol 0.1% every 3 hrs 8 mos Betamethasone sodium phosphate 0.1% every 6 hrs Betamethasone sodium phosphate 0.1% every 4 hrs Betamethasone sodium phosphate 0.1% every 3 hrs Betamethasone sodium phosphate 0.1% every 3 hrs Betamethasone sodium phosphate 0.1% every 3 hrs Fluorometholone alcohol 0.1% every 3 hrs 18 mos Betamethasone sodium phosphate 0.1% every 6 hrs left eye. 17 mos 8 mos 12 mos 8 mos 12 mos 5 mos 13 mos 29 mos 29 mos 12 mos 11 mos 9 mos 9 mos 13 mos 8 mos Systemic Steroid Prednisone 30 mg every day Prednisone 30 mg every day Prednisone 30 mg every day Intolerant to systemic steroids Intolerant to systemic steroids Prednisone 20 mg every day Prednisone 30 mg every day Intolerant to systemic steroids Prednisone 20 mg every day Prednisone 20 mg every day Prednisone 20 mg every day Prednisone 30 mg every day Prednisone 30 mg every day Prednisone 20 mg every day Prednisone 30 mg every day Prednisone 30 mg every day Prednisone 20 mg every day Prednisone 30 mg every day 10 mos 2 mos 2 mos 5 mos 2 mos 29 mos 29 mos 2 mos 5 mos 3 mos 4 mos 9 mos 13 mos 8 mos 8 mos

(OD) (OS)

(OD) (OS)

OD

right eye; OS

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received oral corticosteroids and/or acetazolamide, and the cystoid macular edema biomicroscopically cleared in four eyes within 2 to 9 months. Overall, slit-lamp biomicroscopy showed that cystoid macular edema had cleared completely in 14 eyes (78%) within 9 months postoperatively. Resolution of cystoid macular edema was conrmed by uorescein angiography in 11 eyes and by optical coherence tomography in 3 eyes; a typical case is illustrated in Figure 2. One eye (6%) continued to show macular edema, albeit of minimal severity, and three eyes (17%) remained unchanged biomicroscopically. Nine eyes underwent peeling of the epiretinal membrane or posterior vitreous cortex, and the macular edema resolved in seven of these eyes (78%). The other nine eyes had posterior vitreous detachment without an epiretinal membrane, and the macular edema also resolved in seven of these eyes (78%). No intraoperative complications were noted. Postoperative complications included cataract formation in seven eyes, glaucoma in four eyes with optic nerve atrophy in one, epiretinal membrane formation in one eye, and tractional retinal detachment in one eye. No severe postoperative inammation was observed. Elevated intraocular pressure in four eyes was controlled with topical steroids and antiglaucoma agents. Subsequent surgeries consisted of cataract extraction in six eyes and membrane peeling and silicone oil tamponade in one eye.

Figure 1. Scatter plot of preoperative and postoperative visual acuities of eyes treated in this study.

extrusion needle in four eyes, and the epiretinal membrane was peeled with a microforceps in ve eyes. Complete removal of the vitreous to the vitreous base was performed with scleral depression. Endolaser photocoagulation was performed in two eyes that had overt vasoproliferative changes. Cryocoagulation was not performed. Vitrectomy was performed in only those eyes in which inammation in the anterior chamber had been suppressed by topical steroid therapy. Preoperative oral steroids were stopped in all but three patients by 2 weeks before surgery to wash out the effect of systemic treatment. Postoperative management consisted of topical corticosteroids alone. Systemic and/or periocular corticosteroids and/or acetazolamide were used only when cystoid macular edema had not resolved within 4 weeks. All eyes underwent routine examination, including slit-lamp biomicroscopy after surgery. Fluorescein angiography was done postoperatively in all but two eyes. Optical coherence tomography19 was used in four eyes.

Discussion
Corticosteroid therapy is the primary treatment for cystoid macular edema caused by chronic uveitis. Visual improvement commonly occurs after periocular or systemic steroid treatment for cystoid macular edema caused by pars planitis,20 and most patients with sarcoidosis also respond favorably to this form of therapy.21 If the cystoid macular edema persists, or if periocular or systemic corticosteroid treatment is contraindicated, other therapeutic regimens need to be considered. Dugel and associates15 reported improvement in cystoid macular edema after vitrectomy in all patients with pars planitis. Our study demonstrated complete regression of cystoid macular edema in 14 of 18 eyes and partial regression in 1 of 18 eyes with sarcoid uveitis treated with vitrectomy. Although postoperative medications, including corticosteroids and acetazolamide, were required in some patients, most were treated favorably with vitrectomy alone. The mechanism of regression of cystoid macular edema after pars plana vitrectomy is unclear. Diamond and Kaplan,22 pioneers of therapeutic vitrectomy for uveitis, suggested that removal of inammatory mediators in the vitreous gel had a benecial effect on macular edema. Accumulation in the vitreous of T cells with various cytokine proles is thought to play an important role in the pathogenesis of different types of chronic uveitis.23,24 It has been reported that T cell clones derived from the vitreous humor of patients with sarcoidosis produce a large amount of cytokines, including interleukin-1 and interleukins-6, and -8, and that this increased production of cytokines is not suppressed by corticosteroids.25 Therefore, removal of inammatory cells and cytokines may lead to suppression of the ocular inammation and to recovery of responsiveness to corticosteroids. Mechanical factors have been proposed to explain pseudophakic12,14 and diabetic macular edema.13,26,27 Eyes with

Results
Ten eyes (56%) gained 2 or more lines of Snellen visual acuity at 1 to 12 months after surgery, and 10 eyes (56%) achieved visual acuity of 20/40 or better at the nal visit (Fig 1). However, six eyes (33%) remained unchanged, and two eyes (11%) lost 2 or more lines of Snellen visual acuity. Eight eyes underwent combined lensectomy vitrectomy; ve of these eyes (63%) gained 2 or more lines of Snellen visual acuity at 1 to 12 months after surgery, and four of these eyes (50%) achieved visual acuity of 20/40 or better at the nal visit. The other 10 eyes underwent vitrectomy alone; 5 of these eyes (50%) gained 2 or more lines of Snellen visual acuity at 1 to 12 months after surgery, and 6 of these eyes (60%) achieved visual acuity of 20/40 or better at the nal visit. Preoperative cystoid macular edema cleared by slit-lamp examination in 10 eyes within 0 to 9 months after surgery without additional medical treatment. Those patients with no decrease in macular thickening (seven eyes) in the early postoperative period

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Figure 2. Patient 1, right eye. A, Preoperative venous phase uorescein angiogram shows dye leakage in the macular area. B, Tomographic section shows a large cystic space involving the fovea. C, Fluorescein angiogram 1 month after pars plana vitrectomy shows reduction in dye leakage. D, Tomographic section shows resolution of the macular edema. Note recovery of the foveal depression.

peripheral uveitis and posterior vitreous adhesion reportedly have a greater incidence of macular edema and a less favorable visual prognosis than do eyes with complete posterior vitreous detachment.28 However, in our series, peeling of posterior vitreous cortex and epiretinal membranes had no benecial effect on macular edema. Visual outcome is thought to depend on the duration and severity of cystoid macular edema.29 Long-standing edema is often associated with irreversible damage to macular function even before the development of a full-thickness macular hole. However, no correlation between duration of edema and improvement in vision was found in our study. It is possible that most of the cases in our series were of relatively recent onset and thus resolved without signicant damage to the macula. Unfortunately, the subgroup of patients who will benet most from vitrectomy remains to be identied. Several authors have strongly suggested that complete removal of the vitreous may improve the long-term prognosis.22,31 Furthermore, complete removal of the anterior hyaloid gel may reduce postoperative cyclic membrane formation that can lead to tractional detachment of the peripheral retina and ciliary body.31 For this reason, we performed combined lensectomy vitrectomy in eight eyes with mild lens opacities. The improved vision in these combined

lensectomy vitrectomy patients may be due partially to the lensectomy, although visual improvement occurred regardless of combined lensectomy vitrectomy or vitrectomy alone at 1 to 12 months postoperatively and invariably followed complete resolution of macular edema. Moreover, none of our patients had signicant cataracts before their vitrectomy surgery. It was our impression that the recovery of vision was due primarily to resolution of the macular edema rather than to the lens removal. Cataract formation was the most common complication after pars plana vitrectomy, although the extreme high incidence (100%) may be related to the patients ages (mean, 53 years). It is possible that cataract formation led to the decreased postoperative visual acuity in some patients. Recurrent epiretinal membrane with reduced visual acuity was found in one patient, and tractional retinal detachment occurred in another. During the revised vitrectomy, residual vitreous was noted to have formed a thick brinoid membrane in the periphery, so complete removal of vitreous gel may be essential to preclude postoperative complications associated with residual vitreous traction. In conclusion, our ndings suggest that pars plana vitrectomy has a benecial effect on sarcoidosis-induced cystoid macular edema that is resistant to medical treatment. The limitations of this study include the lack of a control

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group, the use of Snellen visual acuity, and the various durations of follow-up. Accordingly, a prospective and controlled clinical trial is needed to ascertain the actual effectiveness of pars plana vitrectomy for this condition.
sponsive to corticosteroids. A preliminary study. Ophthalmology 1992;99:1535 41. Verbraeken H. Therapeutic pars plana vitrectomy for chronic uveitis: a retrospective study of the long-term results. Graefes Arch Clin Exp Ophthalmol 1996;234:288 93. Dana MR, Merayo-Lloves J, Schaumberg DA, Foster CS. Prognosticators for visual outcome in sarcoid uveitis. Ophthalmology 1996;103:1846 53. Li HK, Abouleish A, Grady J, et al. Sub-Tenons injection for local anesthesia in posterior segment surgery. Ophthalmology 2000;107:41 6; discussion 46 7. Huang D, Swanson EA, Lin CP, et al. Optical coherence tomography. Science 1991;254:1178 81. Godfrey WA, Smith RE, Kimura SJ. Chronic cyclitis: corticosteroid therapy. Trans Am Ophthalmol Soc 1977;74:178 88. Jones NP. Uveitis: An Illustrated Manual. Boston: Butterworth-Heinemann, 1998. Diamond JG, Kaplan HJ. Lensectomy and vitrectomy for complicated cataract secondary to uveitis. Arch Ophthalmol 1978;96:1798 804. Moller DR. Cells and cytokines involved in the pathogenesis of sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 1999;16: 24 31. Muhaya M, Calder VL, Towler HM, et al. Characterization of phenotype and cytokine proles of T cell lines derived from vitreous humour in ocular inammation in man. Clin Exp Immunol 1999;116:410 4. Sakaguchi M, Sugita S, Sagawa K, et al. Cytokine production by T cells inltrating in the eye of uveitis patients. Jpn J Ophthalmol 1998;42:262 8. Tachi N, Ogino N. Vitrectomy for diffuse macular edema in cases of diabetic retinopathy. Am J Ophthalmol 1996;122: 258 60. Lewis H, Abrams GW, Blumenkranz MS, Campo RV. Vitrectomy for diabetic macular traction and edema associated with posterior hyaloidal traction. Ophthalmology 1992;99: 7539. Hikichi T, Trempe CL. Role of the vitreous in the prognosis of peripheral uveitis. Am J Ophthalmol 1993;116:4015. Nussenblatt RB, Kaufman SC, Palestine AG, et al. Macular thickening and visual acuity. Measurement in patients with cystoid macular edema. Ophthalmology 1987;94:1134 9. Suzuma K, Kita M, Yamana T, et al. Quantitative assessment of macular edema with retinal vein occlusion. Am J Ophthalmol 1998;126:409 16. Heiligenhaus A, Bornfeld N, Foerster MH, Wessing A. Longterm results of pars plana vitrectomy in the management of complicated uveitis. Br J Ophthalmol 1994;78:549 54.

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