CONTROVERSIES IN CARE

Pars Plana Vitrectomy for the Induction of Drug-free Remission in Uveitis?

EDITED BY Michael Colucciello, MD

Theoretically, pars plana vitrectomy provides three main potential benefits for patients with chronic intermediate or posterior uveitis: (1) the removal of the depot effect of the vitreous and of contained immune-active cells (constantly producing cytokines) may treat macular edema (Figure 1); (2) the clearance of debris and floaters; and (3) peeling of epiretinal membranes and the internal limiting membrane removes the tractional component involved in the genesis of macular edema.^1-4

Figure 1. Vitreous precipitates anterior to the temporal macula in a patient with sarcoid retinal periphlebitis (note the sheathing around the veins infratemporal, superior and nasal to the disc).

The first reported use of vitrectomy in the treatment of chronic uveitis associated with cataracts, by Diamond and Kaplan in 1978,⁵ demonstrated an improvement in visual acuity in many of the 15 eyes in the series, in which combined vitrectomy with lensectomy was frequently associated with a decrease in CME (Figure 2) and a reduction in the rate of recurrence of the primary disease.

Figure 2. Cystoid macular edema (SD-OCT insert) associated with birdshot chorioretinopathy in an HLA-A29-positive patient.

Therapeutic pars plana vitrectomy was subsequently reported in a series of 14 eyes with various types of chronic uveitis by Algvere et al. in 1981, with improvement of vision noted in 10 of the 14 patients after pars plana vitrectomy surgery, associated with decreased signs of inflammation.⁶ Kaplan promoted the idea that pars plana vitrectomy was an alternative to systemic immunosuppression in treating intermediate uveitis.⁷

Two series reported in 2001 demonstrate that pars plana vitrectomy may play a role in the treatment of in termediate uveitis associated with re fractory macular edema. Stavrao et al.⁸ reported a retrospective study of 37 eyes with uveitis with CME. Following pars plana vitrectomy with out ILM peeling, 12 of 37 (32.4%) had resolution of CME, and 20 of 37 (46.5%) improved by more than two Snellen lines. Eleven of the 25 remaining eyes had >20/30.

Wiechens et al.⁹ reported that 18 of 42 eyes with chronic (refractory to corticosteroid and immunosuppressant treatment) CME had resolution of CME and visual acuity improvement of more than two Snellen lines with a mean 20-month follow-up. Medical therapy could be reduced or discontinued in most cases postvitrectomy.

As Becker and Davis’s superb literature review, published in 2005,¹⁰ states — and it is still valid today — the suggestive evidence from isolated case series that pars plana vitrectomy is useful for the treatment of visual or disease outcomes in uveitis needs to be confirmed by large, well-designed, randomized, controlled, collaborative studies. Subgroups that may respond especially well remain to be identified. Until such studies are completed, this treatment will remain controversial.

This month, we are fortunate to have perspectives on this issue from Marc de Smet, MD, PhD, professor of ophthalmology at the Center for Specialized Ophthalmology Lausanne, Switzerland, and Albert Vitale, MD, professor of ophthalmology and visual sciences at the University of Utah School of Medicine/Moran Eye Center.

REFERENCES

1. Dugel PU, Rao NA, Ozler S, et al. Pars plana vitrectomy for intraocular inflammation-related cystoid macular edema unresponsive to corticosteroids. A preliminary study. Ophthalmology. 1992;99: 535-541.
2. Mieler WF, Will BR, Lewis H, et al. Vitrectomy in the management of peripheral uveitis. Ophthalmology. 1988;95:859-864.
3. Heiligenhaus A, Bornfeld N, Foerster MH, et al. Long-term results of pars plana vitrectomy in the management of complicated uveitis. Br J Ophthalmol. 1994;78:549-554.
4. Okhravi N, Lightman S. Cystoid macular edema in uveitis. Ocul Inflamm Inflamm. 2003;11: 29-38.
5. Diamond JG, Kaplan HJ. Lensectomy and vitrectomy for complicated cataract secondary to uveitis. Arch Ophthalmol. 1978;96:1798-1804.
6. Algvere P, Alanko H, Dickhoff K, et al. Pars plana vitrectomy in the management of intraocular inflammation. Acta Ophthalmol (Copenh). 1981; 59:727-736.
7. Kaplan HJ. Surgical treatment of intermediate uveitis. Dev Ophthalmol. 1992;23:185-189.
8. Stavrou P, Baltatzis S, Letko E, et al. Pars plana vitrectomy in patients with intermediate uveitis. Ocul Inflamm Inflamm. 2001;9:141-151.
9. Wiechens B, Nolle B, Reichelt JA. Pars-plana vitrectomy in cystoid macular edema associated with intermediate uveitis. Graefes Arch Clin Exp Ophthalmol. 2001;239:474-481.
10. Becker M, Davis J. Perspectives: Vitrectomy in the treatment of uveitis. Am J Ophthalmol. 2005;140: 1096-1105.

It’s Too Soon to Tell if PPV is the Right Way to Go in Treating Uveitis

Albert Vitale, MD

Vitreoretinal surgery has a definitive role in the management of acute postoperative endophthalmitis following cataract surgery as defined by the Endophthalmitis Vitrectomy Study (EVS).¹ It is also important in clearing the visual axis and repairing the structural complications associated with select infectious uveitic entities, such as toxoplasmosis,^2,3 toxocariasis⁴ and necrotizing herpetic retinitis,⁵ in the management of cy clitic proliferations complicating hypotony,⁶ and in patients with lens-induced uveitis,⁷ in which it can effect a drug-free cure for inflammation.

However, the therapeutic role of pars plana vitrectomy (PPV) in the management of noninfectious intermediate or posterior uveitis or panuveitis is less well defined. It has been suggested that PPV may serve as an alternative to or be used adjunctively with systemic immunomodulatory therapy (IMT) in modulating the course of uveitis with a reduction of inflammatory recurrences, attenuation of macular edema, and a diminished requirement for the use of anti-inflammatory drugs with improved visual function.

Permanent removal of antigenic material and of proinflammatory mediators from the vitreous cavity is hypothesized to effect a change in the immunologic milieu of the eye that promotes inflammatory control and facilitates the efficacy of anti-inflammatory drug therapy. Indeed, numerous proinflammatory cytokines, such as IL-1, IL-2, TNF-α, IL-6, IL-10, IFN-γ, SVCAM, RANTES and IP-10, have been isolated from the aqueous and vitreous of patients with active uveitis.^8,9

The presence of autologous foreign material, such as type-2 collagen,¹⁰ and the demonstration of intraocular antibodies to and the DNA of infectious organisms in the vitreous of eyes with quiescent uveitis support the concept of the vitreous as a reservoir of immunoreactive material.^11,12 Vitrectomy is thought to re move not only autoantigens but also autoreactive helper T-cells, thereby modulating the inflammatory stimulus much like removing lens protein from the eye of a patient with phacogenic uveitis.

With the creation of a unicameral state, PPV and lensectomy are thought to promote an immunologically more tolerant environment,¹³ allowing for the diffusion of anti-inflammatory cytokines, such as TGF-b, which is elaborated by the trabecular cells,¹⁴ and the upper regulation of T regulatory cells and the maintenance of a downregulatory immune state.¹⁵

Finally, vitrectomy is thought to improve the penetration of systemic medications, allowing for the reduction of dosage requirements for in flammatory control. With regard to inflammatory macular edema, cytokines and chemokines not only induce vascular leakage but also promote firm attachment of the vitreous to the macula, with subsequent fibrosis and contraction of the posterior hyaloid and/or ILM, creating tractional forces and the maintenance of chronic macular edema.^{16, 17} Separation of the posterior hyaloid and the ILM before irreversible damage to the RPE-photoreceptor complex has occurred may relieve medically refractory uveitic macular edema.

Since the initial description of the use of vitrectomy and lensectomy in the management of complicated uveitic cataract by Diamond and Kaplan in 1978,¹⁸ there have been numerous reports describing the therapeutic benefit of vitrectomy in the management of uveitis and of its complications. However, until recently, no prospective, con trolled studies had been performed to evaluate critically its role as a single or com bined procedure for this indication.

Becker and Davis conducted a superb review of the literature and provided a discussion of the subject on the basis of 44 retrospective, non-comparative, interventional series between 1981 and 2005, comprising nearly 1,800 eyes of 1,600 patients.¹⁹ Their review of the literature suggests that PPV is possibly relevant to the outcomes of improving vision and reducing inflammation and CME, particularly among patients with intermediate uveitis, who comprised nearly 50% of these eyes.

Among the uncontrolled reports for which data were available, a nearly uniform clearing of the vitreous following PPV was reported, with a decreased need for systemic medication postoperatively noted by 25 of 44 authors. Among the more recent reports, a statistically significant decrease in the recurrence rate following PPV has been reported among both adult²⁰ and pediatric patients.²¹

The putative therapeutic benefit of vitrectomy prior to the implementation of IMT, failing more conservative treatment with periocular or systemic corticosteroids, is mentioned most often in the context of intermediate and pediatric uveitis. However, it is not clear whether vitrectomy should precede systemic IMT, as proposed by Kaplan²² in his four-step algorithm for the management of intermediate uveitis, or whether all patients should receive preoperative IMT.

In an effort to address this longstanding dilemma, Quinones and colleagues²³ performed a prospective, randomized pilot study comparing PPV to IMT among 16 patients with recalcitrant intermediate uveitis and reduced vision to the level of 20/30 despite periocular and systemic corticosteroids. Nine patients were randomized to surgery and 11 to medical therapy with IMT. Patients failing medical therapy underwent rescue vitrectomy.

Although no statistically significant differences in outcome measurements (vision, intraocular pressure, and level of intraocular inflammation) were found during the initial 18 months of follow-up, due in large part to the underpowered nature of this pilot study, several important clinically relevant trends were observed. Resolution of inflammation was achieved in 82% of eyes following vitrectomy on no systemic treatments, as compared to 43% of eyes treated medically. Moreover, four out of seven of these patients required vitrectomy, representing a fairly significant failure rate in the medically treated group.

Improvement in visual acuity, while initially favoring IMT at month 6, reversed at month 12 and was sustained among the eyes undergoing vitrectomy at 18 months. Likewise, IOP reduction was achieved in more patients undergoing vitrectomy than IMT. Resolution of presenting macular edema was achieved in three of three eyes undergoing vitrectomy and in two of three eyes in the IMT group. There were no intraoperative complications, and a reversible leukopenia and anemia were seen in two patients undergoing medical therapy. Cataract progression was observed in both groups.

The safety and efficacy of PPV in the management of recalcitrant pediatric uveitis has been described in several retrospective reports, including that by Trittibach and coworkers²¹ in 29 eyes of 23 consecutive patients with statistically significant improvement in logMAR VA (0.91 to 0.33 ), a reduction in the percentage of eyes with uveitic relapses, and CME postoperatively. Low preoperative logMAR VA and the presence of CME were the most accurate predictors of final functional visual outcome.

Most recently, Giuliari and colleagues²⁴ reported their experience with vitrectomy in the management of 28 eyes of 20 pediatric patients with active uveitis with or without medical therapy, followed for a mean of 13.5 months. Diagnoses ranged from pars planitis, idiopathic panuveitis, and JIA-associated iridocyclitis, among which six eyes had associated retinal vasculitis. At the most recent follow-up, 96% of the patients achieved inflammatory control with or without concomitant medical therapy, including five or six patients with persistent retinal vasculitis.

Although there was a modest reduction in the need for systemic IMT postoperatively, it should be noted that no eyes had been adequately controlled prior to surgery. Vitrectomy was thought to contribute to inflammatory control in patients with recalcitrant uveitis, especially those with retinal vasculitis, which is known to require more aggressive therapy, possibly allowing for lower doses and a shorter duration of immunomodulatory medications. Mean BCVA improved at all time points.

The procedures performed concurrently with PPV included cataract extraction in six eyes, four of which received an IOL and two of which were left aphakic, IOL extraction in one eye, endolaser, cryotherapy and intravitreal injections of triamcinolone acetonide or bevacizumab. Intraoperative retinal tears were noted in two eyes undergoing 20-gauge PPV, with the development of a rhegmatogenous retinal detachment one week postoperatively. Cataracts progressed in four eyes with preoperative clear lenses within six months of surgery.

Pars plana vitrectomy has been employed successfully for inflammatory CME refractory to medical therapy, especially in the presence of concomitant structural complications, such as ERM or vitreomacular traction, seen clinically or on OCT. The presence of ERM has been shown to be significantly associated with the failure of medical treatment for CME.²⁵

Case selection is critical, as patients with chronic CME and permanent architectural damage, such as the presence of fixed cysts seen clinically, widening of the foveal avascular zone on FA, and foveal atrophy with attenuation of central retinal thickness demonstrated on OCT, are less likely to respond to surgery.

In their review of the literature, Becker and Davis¹⁹ noted that vitrectomy was beneficial in the management of uveitic macular edema in 19 publications, with a reduction in the median percentage of patients with CME from 36% preoperatively to 18% postoperatively. More recently, vitrectomy with ILM peeling and intravitreal triamcinolone was shown to improve CME, with concomitant improvement in visual acuity in 19 patients with refractory uveitic macular edema examined retrospectively.²⁶

Schaal and colleagues¹⁶ likewise noted a rapid decrease in retinal thickness and improvement in visual acuity in many of their patients with refractory uveitic CME following 25-gauge PPV and triamcinolone-assisted visualization and separation of the posterior hyaloid. In eyes with an abnormal glistening reflex of the ILM noted either preoperatively or intraoperatively, the authors advocate removal of both the adherent posterior hyaloid and peeling of the ILM in an effort to enhance the resolution of CME.

A prospective, randomized pilot study was undertaken by Tranos and colleagues²⁷in 23 patients with quiescent intermediate or posterior uveitis with CME refractory to medical therapy, all of whom had been on systemic steroids or IMT for at least three months. Patients were randomized to either surgery or continued medical treatment, with the surgical arm receiving preoperative corticosteroids tapered to postoperative levels within three to six weeks.

While there was a statistically significant improvement in logMAR vision in the surgically vs medically treated eyes at six months, this was not necessarily accompanied by angiographic improvement in macular edema. In fact, there was no statistically significant improvement in either group from baseline with regard to angiographic scores of macular edema.

It is possible that the improvement in vision was mediated by improved media clarity following vitrectomy. Inflammatory activity was noted to improve with regard to vitritis, but not anterior chamber cells, and there was a similar reduction in the need for medical therapy between the two groups. There were no significant intraoperative or postoperative complications. Overall, it was suggested that vitrectomy might benefit visual function in patients with uveitic macular edema; however, no definitive conclusions could be drawn based on the small patient numbers in this pilot study.

While biologically plausible hypotheses and clinical experience based on a review of the literature is highly suggestive of improved outcomes, the question of whether and in which patients PPV can induce a permanent drug-free remission and PPV’s definitive role in the management of noninfectious intermediate and posterior uveitis and panuveitis will require prospective, hypothesis-driven, randomized, controlled, collaborative trials.

Specifically, defined uveitic populations and controls, careful documentation of concomitant medical therapy, standardization and precise reporting of vision, macular edema, and intraocular inflammation, together with surro gate markers for inflammatory activity, such as fluorescein angiography, to detect vascular leakage, intraocular cytokine levels, and electrophysiologic abnormalities will be essential in moving forward. These measure will allow for definitive recommendations to be made as to the place of vitrectomy in our therapeutic stepladder and for the identification of patients for whom surgery carries less risk and a reduced burden with regard to adverse side effects and the costs associated with prolonged systemic treatment with IMT and biological agents.

REFERENCES

1. Lemley CA, Han DP. Endophthalmitis: a review of current evaluation and management. Retina. 2007;27:662-680.
2. Fitzgerald CR. Pars plana vitrectomy for vitreous opacity secondary to presumed toxoplasmosis. Arch Ophthalmol. 1980;98:321-323.
3. Papadopoulou DN, Petropoulos IK, Mangioris G, Pharmakakis NM, Pournaras CJ. Pars plana vitrectomy in the treatment of severe complicated toxoplasmic retinochoroiditis. Eur J Ophthalmol. 2011; 21:83-88.
4. Belmont JB, Irvine A, Benson W, O’Connor GR. Vitrectomy in ocular toxocariasis. Arch Ophthalmol. 1982;100:1912-1915.
5. Ahmadieh H, Soheilian M, Azarmina M, Dehghan MH, Mashayekhi A. Surgical management of retinal detachment secondary to acute retinal necrosis: clinical features, surgical techniques, and long-term results. Jpn J Ophthalmol. 2003;47:484-491.
6. Gupta P, Gupta A, Gupta V, Singh R. Successful outcome of pars plana vitreous surgery in chronic hypotony due to uveitis. Retina. 2009;29:638-643.
7. Smith GT, Vakalis AN, Brittain GP, Casswell AG. Vitrectomy for phacolytic glaucoma in a patient with homocystinuria. Am J Ophthalmol. 1999;128: 762-763.
8. Perez VL, Papaliodis GN, Chu D, Anzaar F, Christen W, Foster CS. Elevated levels of interleukin 6 in the vitreous fluid of patients with pars planitis and posterior uveitis: the Massachusetts eye & ear experience and review of previous studies. Ocul Immunol Inflamm. 2004;12:193-201.
9. van Kooij B, Rothova A, Rijkers GT, de Groot-Mijnes JD. Distinct cytokine and chemokine profiles in the aqueous of patients with uveitis and cystoid macular edema. Am J Ophthalmol. 2006;142:192-194.
10. Opremcak EM SD, Cowans AB. Cell mediated autoimmune mechanisms in uveitis. Invest Ophthalmol Vis Sci. 1993;34:1104.
11. Quentin CD, Reiber H. Fuchs heterochromic cyclitis: rubella virus antibodies and genome in aqueous humor. Am J Ophthalmol. 2004;138:46-54.
12. Nguyen QD, Humphrey RL, Dunn JP, Humayun MS. Elevated vitreous concentration of monoclonal immunoglobulin manifesting as schlieren in juvenile rheumatoid arthritis-associated uveitis. Arch Ophthalmol. 2001;119:293-296.
13. Streilein JW. Anterior chamber associated immune deviation: the privilege of immunity in the eye. Surv Ophthalmol. 1990;35:67-73.
14. Tripathi RC, Li J, Borisuth NS, Tripathi BJ. Trabecular cells of the eye express messenger RNA for transforming growth factor-beta 1 and secrete this cytokine. Invest Ophthalmol Vis Sci. 1993;34:2562-2569.
15. Yeh S, Li Z, Forooghian F, Hwang FS, et al. CD4+Foxp3+ T-regulatory cells in noninfectious uveitis. Arch Ophthalmol. 2009;127:407-413.
16. Schaal S, Tezel TH, Kaplan HJ. Surgical intervention in refractory CME—role of posterior hyaloid separation and internal limiting membrane peeling. Ocul Immunol Inflamm. 2008;16:209-210.
17. Ossewaarde-van Norel A, Rothova A. Clinical review: Update on treatment of inflammatory macular edema. Ocul Immunol Inflamm. 2011;19: 75-83.
18. Diamond JG, Kaplan HJ. Lensectomy and vitrectomy for complicated cataract secondary to uveitis. Arch Ophthalmol. 1978;96:1798-1804.
19. Becker M, Davis J. Vitrectomy in the treatment of uveitis. Am J Ophthalmol. 2005;140:1096-1105.
20. Scott RA, Haynes RJ, Orr GM, Cooling RJ, Pavesio CE, Charteris DG. Vitreous surgery in the management of chronic endogenous posterior uveitis. Eye (Lond). 2003;17:221-227.
21. Trittibach P, Koerner F, Sarra GM, Garweg JG. Vitrectomy for juvenile uveitis: prognostic factors for the long-term functional outcome. Eye (Lond). 2006;20:184-190.
22. Kaplan HJ. Surgical treatment of intermediate uveitis. Dev Ophthalmol. 1992;23:185-189.
23. Quinones K, Choi JY, Yilmaz T, Kafkala C, Letko E, Foster CS. Pars plana vitrectomy versus immunomodulatory therapy for intermediate uveitis: a prospective, randomized pilot study. Ocul Immunol Inflamm. 2010;18:411-417.
24. Giuliari GP, Chang PY, Thakuria P, Hinkle DM, Foster CS. Pars plana vitrectomy in the management of paediatric uveitis: the Massachusetts Eye Research and Surgery Institution experience. Eye (Lond). 2010;24:7-13.
25. Markomichelakis NN, Halkiadakis I, Pantelia E, et al. Course of macular edema in uveitis under medical treatment. Ocul Immunol Inflamm. 2007;15:71-79.
26. Gutfleisch M, Spital G, Mingels A, Pauleikhoff D, Lommatzsch A, Heiligenhaus A. Pars plana vitrectomy with intravitreal triamcinolone: effect on uveitic cystoid macular oedema and treatment limitations. Br J Ophthalmol. 2007;91:345-348.
27. Tranos P, Scott R, Zambarakji H, Ayliffe W, Pavesio C, Charteris DG. The effect of pars plana vitrectomy on cystoid macular oedema associated with chronic uveitis: a randomised, controlled pilot study. Br J Ophthalmol. 2006;90:1107-1110.

When Considering Surgery, Proceed Only With Caution

Marc De Smet, MD, PhD, FRCSC

Ocular inflammation is characterized by recurrences and exacerbations. It may occur as the result of an infection or an autoimmune process, affecting only the eye or heralding a systemic disease. Chronicity and recurrences lead to vision loss and permanent structural alterations. Therapy is aimed at maintaining vision and limiting damage for as long as there is inflammation, which in many cases is lifelong.

Diamond and Kaplan were the first to propose vitrectomy and lensectomy as a means of improving vision in these patients.¹ Several mechanisms have been proposed to explain the apparent benefit of vitrectomy, including the elimination of trapped antigens and inflammatory mediators, modification of the immune profile, and better diffusion of medications into the eye.^2-4

However, ocular surgery does not eliminate the basic disease process, and complications are not infrequent; control of inflammation by medical means in the perioperative period is essential.^1,4-7 Postoperative disease recurrence may be more recalcitrant if patients do not receive adequate perioperative immunosuppression, including an increased risk of developing proliferative vitreoretinopathy.^8,9

Hence, surgery has a role to play in ocular inflammation, but as with all therapies, its precise role and place in the management strategy requires careful assessment. For example, in post-cataract endophthalmitis, based on the proposed mechanisms, vitrectomy should have a decisive effect on vision recovery, yet the Endophthalmitis Vitrectomy Study showed that it was of benefit only in those patients with hand motions vision or less.¹⁰ More than 15 years later, despite more sophisticated surgical tools, these recommendations have not been changed.

Does vitrectomy provide shortor long-term control?

Becker and Davis, in their review of the literature, concluded that vitrectomy was particularly relevant in patients with macular edema.⁶ While surgery improved postoperative visual acuity and reduced the prevalence of macular edema, it did not eliminate it.

In a review published in 2003, Becker reported that 38% of patients undergoing a therapeutic vitrectomy (1,934 eyes) had macular edema. Surgery reduced this rate to 20%.¹¹ Because all of the patients received immunosuppression or saw their immunosuppression raised in the perioperative period, some of the observed improvement may have been related to the medical therapy rather than the surgery itself.

Some studies have shown the effects of surgery to be transient, with vision dropping back to preop levels or worse over a 12- to 18-month period.^12-14 Similarly, control of inflammation in chronic cases is often temporary.^14-16

In juvenile idiopathic arthritis, vitrectomy reduced the number of relapses from 62% to 30%, but at the risk of developing cataracts, PVR or phthisis.¹⁷ These results should be contrasted with those achieved using recent treatment guidelines for systemic therapy.¹⁸

Tight systemic control, based on expert panel guidelines, as was used in the MUST trial, led to a reduction in macular edema on medication alone from 75% to 30% at 24 months.¹⁹ Temporary use of cyclophosphamides leads to control of intraocular inflammation on low-dose immunosuppression in 89% of cases at one year, and a 75% rate of remission was achieved at three years.^20,21 These figures are similar to, if not better than, those achieved in many vitrectomy series.

What is the risk-benefit relationship?

Therapy for uveitis requires individualization. As indicated above, immunosuppression can be quite effective with limited local or systemic risk.^19,20,22-24 An alternative not mentioned so far are sustained-release intraocular implants.

The Retisert (Bausch + Lomb) implant can reduce the rate of recurrence from 62% preimplantation to between 4% and 20% over a three-year period, though at the risk of developing cataracts or glaucoma over the same period.^22,23 Significant improvements in vision were also observed over six months with Ozurdex (Allergan). Here a shorter follow-up did not allow for a full assessment of risk, though it may be lower for certain parameters.²⁵

In the absence of large, controlled studies, the risk associated with vitrectomy can only be inferred from reported small case series. The degree of ocular inflammation and surgical skill are factors that play roles, as well as the extent of the surgery. Depending on the entity, more extensive surgery with removal of the vitreous base may be indicated if not required — a more extensive procedure than would be carried out during a standard vitrectomy.^26,27

Aphakia combined with vitrectomy may, in some instances, be the most appropriate approach.²⁶ Most series report complications, with a few patients losing significant vision or developing phthisis bulbi. For these patients, aggressive medical management or delaying surgery until better inflammatory control had been achieved might have been a better option. Common complications included the development of cataract (up to 60% of cases within a year), vitreous hemorrhage, tractional or rhegmatogenous detachments, glaucoma, and proliferative vitreoretinopathy.

When is vitrectomy of particular benefit?

From the existing literature and personal experience, vitrectomy has a role to play in the management of uveitis patients. Resolution of macular traction, peeling of ERMs, management of chronic hypotony and removal of vitreous haze preventing the visualization of the posterior pole are all indications for surgery.^28-30 Vitrectomy’s role in managing complications arising from inadequate or insufficient medical therapy is clear.

However, considering it as an alternative to medical treatment is risky without long-term studies extending over several years. Only with such studies can there be a definitive answer as to the role of vitrectomy in the management of uveitis. RP

REFERENCES

1. Diamond DJ, Kaplan HJ. Lensectomy and vitrectomy for complicated cataract secondary to uveitis. Arch Ophthalmol. 1978;96:1798-1804.
2. el-Shabrawi Y, Livir-Rallatos C, Christen W, et al. High levels of interleukin-12 in the aqueous humor and vitreous of patients with uveitis. Ophthalmology. 1998;105:1659-1663.
3. de Boer JH, van haren MAC, de Vries-Knoppert WAEJ, et al. Analysis of IL-6 levels in human vitreous fluid obtained from uveitis patients, patients with proliferative intraocular disorders and eye bank eyes. Curr Eye Res. 1992;11(Suppl):181-186.
4. Diamond DJ, Kaplan HJ. Uveitis: effect of vitrectomy combined with lensectomy. Ophthalmology. 1979;86:1320-1327.
5. Smith RE, Kokoris N, Nobe JR, et al. Lensectomyvitrectomy in chronic uveitis. Trans Am Ophthalmol Soc. 1983;81:261-273.
6. Becker MD, Davis J. Vitrectomy in the treatment of uveitis. Am J Ophthalmol. 2005;140:1096-1105.
7. de Smet MD, Okada AA. Cystoid macular edema in uveitis. Dev. Ophthal. 2010;47:136-147.
8. Girard P, Mimoun G, Karpouzas I, Montefiore G. Clinical risk factors for proliferative vitreoretinopathy after retinal detachment surgery. Retina. 1994; 14:417-424.
9. Heiligenhaus A, Bornfeld N, Wessing A. Long-term results of pars plana vitrectomy in the management of intermediate uveitis. Curr Opin Ophthalmol. 1996;7:77-79.
10. Endophthalmitis Vitrectomy Study Group. Results of the endophthalmitis vitrectomy study: A randomized trial of immediate and of intravenous antibiotics for the treatment of postoperative bacterial endophthalmitis. Arch Ophthalmol. 1995;113:1479-1496.
11. Becker MD, Harsch N, Zierhut M, et al. Therapeutic vitrectomy in uveitis. Current status and recommendations. Ophthalmologe. 2003;100:787-795.
12. Wiechens B, Nölle B, Reichelt JA. Pars-plana vitrectomy in cystoid macular edema associated with intermediate uveitis. Graefes Arch Clin Exp Ophthalmol. 2001;239:474-481.
13. Gutfleisch M, Spital G, Mingels A, et al. Pars plana vitrectomy with intravitreal triamcinolone: effect on uveitic cystoid macular oedema and treatment limitations. Br J Ophthalmol. 2007;91:345-348.
14. Nolle B, Eckardt C. Vitrectomy in multifocal chorioretinitis. German J Ophthalmol. 1993;2:14-19.
15. Bovey E, Herbort C. Vitrectomy in the manage ment of uveitis. Ocul Immunol Inflamm. 2000;8:285-291.
16. Bovey EH, Gonvers M, Herblrt CP. Vitrectomie par la pars plana au cours des uveites. Klinik Monatsblätter Augenheilkunde. 1992;200:464-467.
17. Trittibach P, Koerner F, Sarra GM, Garweg JG. Vitrectomy for juvenile uveitis: prognostic factors for the long-term functional outcome. Eye. 2005;20:184-190.
18. Jabs DA, Rosenbaum JT, Foster CS, et al. Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel. Am J Ophthalmol. 2000;130:492-513.
19. Multicenter Uveitis Steroid Treatment (MUST) Trial Research Group; Kempen JH, Altaweel MM, et al. Randomized comparison of systemic antiinflammatory therapy versus fluocinolone acetonide implant for intermediate, posterior, and panuveitis: The Multicenter Uveitis Steroid Treatment Trial. Ophthalmology. 2011;118:1916-1926.
20. Pujari SS, Kempen JH, Newcomb CW, et al. Cyclophosphamide for ocular inflammatory diseases. Ophthalmology. 2010;117:356-365.
21. Kötter I, Gunaydin I, Zierhut M, Stübiger N. The use of interferon α in Behcet disease: review of the literature. Semin Arthritis Rheum. 2004;33:320-325.
22. Pavesio C, Zierhut M, Bairi K, et al. Evaluation of an intravitreal fluocinolone acetonide implant versus standard systemic therapy in noninfectious posterior uveitis. Ophthalmology. 2010;117:567-575.e1.
23. Callanan DG, Jaffe GJ, Martin DF, et al. treatment of posterior uveitis with a fluocinolone acetonide implant: three-year clinical trial results. Arch Ophthalmol. 2008;126:1191-1201.
24. Lowder C, Belfort R Jr, Lightman S, et al. Dexamethasone intravitreal implant for noninfectious intermediate or posterior uveitis. Arch Ophthalmol. 2011;129:545-553.
25. London NJ, Chiang A, Haller JA. The dexamethasone drug delivery system: indications and evidence. Adv Ther. 2011;28:351-366.
26. Kiryu J, Kita M, Tanabe T, et al. Pars plana vitrectomy for epiretinal membrane associated with sarcoidosis. Jpn J Ophthalmol. 2003;47:479-483.
27. Heiligenhaus A, Bornfeld N, Foerster MH, Wessing A. Long term results of pars plana vitrectomy in the management of complicated uveitis. Br J Ophthalmol. 1994;78:549-554.
28. de Smet M, Gunning F, Feenstra R. The surgical management of chronic hypotony due to uveitis. Eye. 2005;19:60-64.
29. Yu EN, Paredes I, Foster CS. Surgery for hypotony in patients with juvenile idiopathic arthritis-associated uveitis. Ocul Immunol Inflamm. 2007;15:11-17.
30. Dev S, Mieler WF, Pulido JS, Mittra RA. Visual outcomes after pars plana vitrectomy for epiretinal membranes associated with pars planitis. Ophthalmology. 1999;106:1086-1090.