Article

Pars Plana Vitrectomy in Uveitis Management

Data are scant on this important tool for diagnosis and treatment of uveitis.

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Pars plana vitrectomy is a valuable and essential tool in the diagnostic and therapeutic armamentarium for vitreoretinal surgeons in the management of uveitis. Since the development of pars plana vitrectomy (PPV) in the 1970s, there have been numerous case reports and series describing the utility of PPV for patients with uveitis. The first large systematic review was performed by Davis and Becker, and examined 44 interventional case series from 1981 to 2005 and included 1,575 patients (1,762 eyes).1 While the review found a benefit in terms of reduction of cystoid macular edema (CME) after PPV, the heterogeneous nature of the case series and patients included in the review limits the application of these conclusions, as the authors acknowledged.

To date, no randomized clinical trial has been undertaken to evaluate the role of PPV in uveitis patients. The goal of this article is to provide a brief overview and discussion of the indications for vitrectomy in uveitis, diagnostic and therapeutic applications, as well as further developments in the past few years.

INDICATIONS

Indications for PPV in uveitis patients include diagnostic vitreous or retinal biopsy; treatment of media opacity (including cataract and vitritis); lens-induced uveitis; treatment of structural complications, such as epiretinal membrane (ERM), retinal detachment (RD), and CME; and intravitreal drug delivery.2

Advancements in PPV techniques, including the use of smaller-gauge vitrectomy, new instruments, intraoperative imaging, and heads-up display, have renewed interest in the use of PPV for management of ERM, a common complication of longstanding uveitis. A recent case series examined the outcomes of ERM peel in 16 patients with a variety of uveitis. After 6 months, VA was improved in 31.25% of eyes, stable in 31.25%, and worse in 37.5%.3

PPV has long been described for treatment of longstanding CME in uveitis, although it is employed less frequently for this reason in the current era. A review in 2001 found a therapeutic benefit for CME in sarcoid patients — 10 of 18 eyes had at least a 2-line improvement in VA at 12 months, although this study was limited by the absence of the use of optical coherence tomography (OCT) imaging to assess for presence of CME.4 PPV has also been described more specifically for ERM associated with pars planitis.5 Macular hole (MH) has also been reported as a rare complication of intermediate, posterior, and panuveitis. However, a recent systematic review of case series did not find sufficient evidence to compare success rates of PPV and ERM peel for MH closure in patients with uveitis.6

Sherveen Salek, MD, is a vitreoretinal fellow at Emory Eye Center, Emory University School of Medicine in Atlanta, Georgia. Steven Yeh, MD, is Louise M. Simpson Professor of Ophthalmology in the Section of Vitreoretinal Surgery & Diseases and the director of the Section of Uveitis and Vasculitis at Emory Eye Center, Emory University School of Medicine. The authors report no related disclosures. Reach Dr. Salek at ssalek@gmail.com.

Editor’s note: This article is featured in a journal club episode of “Straight From the Cutter’s Mouth: A Retina Podcast.” Listen here: "Episode 73: Retinal Physician November 2017 Issue Discussion, PPV for Uveitis/Retinal Tears/Future of Retina."

IMMUNOSUPPRESSION: IS THERE AN OPTIMAL METHOD?

Control of intraocular inflammation, including the use of corticosteroid-sparing agents and biologic therapy, is paramount prior to any surgical intervention in a uveitic eye, including with PPV. A study found that in patients with Behçet disease undergoing PPV, 3 infusions of preoperative infliximab followed by 3 postoperative infusions improved visual outcomes and inflammation.7 While 3 months has been typically cited as the optimal duration of control of inflammation prior to cataract surgery in uveitis patients, there is less consensus with regards to such duration prior to PPV in uveitis patients. If PPV is being performed for diagnostic purposes that may guide sight- or lifesaving therapy, such as lymphoma, then more urgent intervention prior to optimal inflammatory control is clearly justified. Perioperative intravenous steroids followed by a short postoperative oral steroid taper may prevent worsening inflammation.

INTRAOCULAR LYMPHOMA

Primary intraocular lymphoma (PIOL) is a rare but commonly cited masquerade syndrome that can present with vitritis, and may even be responsive to corticosteroids (Figure 1).8 PPV with vitreous biopsy can yield a cytologic diagnosis that guides additional diagnostic testing and intravitreal and systemic chemotherapy.9 Chorioretinal biopsy of subretinal infiltrates may increase the diagnostic yield of PPV for PIOL. An important drawback to consider is that the high volume of fluid generated may decrease the sensitivity; hence core vitreous biopsy with an undiluted specimen may be helpful prior to starting core PPV.10 Testing of ocular fluid in addition to histopathology include cytokine analysis utilizing IL-10: IL-6 ratios, flow cytometry, and gene rearrangement studies (ie, IgH heavy chain and kappa or lambda light chain) for evidence of monoclonal B-cell populations.11

Figure 1. Fundus photo of a 61-year-old patient with a history of systemic large-cell lymphoma more than 15 years prior to presentation. Polymerase chain reaction testing of the aqueous humor was negative for VZV, CMV, HSV, and toxoplasmosis. Diagnostic pars plana vitrectomy showed large-cell lymphoma, establishing a diagnosis of secondary vitreoretinal lymphoma.8

VITRECTOMY FOR INFECTIOUS ETIOLOGIES OF UVEITIS

Retinal detachment has been associated with several infectious inflammatory conditions, including ocular toxoplasmosis (OT) and acute retinal necrosis (ARN). In toxoplasmosis, RD has been reported to be as high as 11.4%, while the rate of RD in ARN is even higher, reported at 59% in a recent series.12 PPV in these cases poses unique technical challenges for the surgeon (Figure 2). Patients undergoing surgical intervention should be optimized on appropriate antibiotic or antiviral therapy to treat the underlying etiology of infection.13 Combination systemic and intravitreal antiviral therapy for ARN, in particular, may improve the likelihood of VA gain and reduce the risk of RD in patients with ARN.14 Other factors including disease severity and adjunctive therapies such as oral prednisone warrant further study. Specifically, while a correlation was found between presence of vitritis and development of RD in patients with OT, there was no benefit to preoperative treatment with oral prednisone, although it should be noted that the sample size was small.

Figure 2. Fundus photos of a patient with diffuse toxoplasmosis chorioretinitis who developed a total retinal detachment with a large atrophic hole superonasal to the optic nerve (A). Following pars plana vitrectomy, endolaser, and silicone oil instillation, retinal reattachment was achieved but the VA remained poor due to optic atrophy and macula-off retinal detachment status (B).

For ARN, the high incidence of RD has led some to propose early vitrectomy to both prevent secondary RD and improve visual prognosis for affected eyes. A retrospective case series found a benefit to early PPV for prevention of RD in eyes with ARN, but did not find a significant difference in VA.15 Subsequent case series have failed to find a benefit for prophylactic PPV for improvement of VA in eyes with ARN.16 However, VA improvement has been noted after PPV once RD has developed secondary to ARN.17 These results are likely confounded by differences in the extent of retinal necrosis, which may impose varying degrees of limits on the visual potential of involved eyes.18 The surgeon should take into account the propensity for recurrent RD in eyes with ARN, and can consider the use of silicone oil for longer term tamponade.19 Long-term assessment of outcomes of RD associated with ARN have shown frequent recurrences of RD in which case the visual prognosis may be guarded and vigilant monitoring is needed.20

DIAGNOSTIC TECHNIQUES

Vitrectomy also has diagnostic utility for infectious causes of uveitis. Just as with suspected intraocular malignancy, an infectious etiology should be considered when a patient fails to respond to topical, local or systemic corticosteroids. Successful diagnostic PPV has been reported using 20-, 23-, and 25-gauge instrumentation.21 The vitreoretinal surgeon’s task is to obtain an adequate core specimen to send for microbiology, cytology, or polymerase chain reaction (PCR) testing. Media opacity from vitritis or uveitic cataract can make this task difficult. A meticulous peripheral vitrectomy may not be necessary in these cases to avoid iatrogenic peripheral retinal breaks. However, careful inspection of peripheral retina with scleral depression is recommended to avoid postoperative complications. An undiluted specimen will facilitate correct diagnosis, particularly in cases where a specific concentration is needed (eg, viral load, cytokine concentration). A 3-mL syringe can be attached to the vitreous cutter, with a 3-way stopcock to switch between manual and automated aspiration from the syringe and vitrector, respectively. The peripheral retina should be carefully monitored for formation of choroidal effusions.22 Once the undiluted specimen has been collected, automated fluid infusion is restored and a second syringe is used to collect up to 10 mL of a dilute vitreous specimen. During the course of vitrectomy, the surgeon may encounter additional areas of dense loculated or consolidated vitreous debris. Additional direct manual aspiration of these areas using the above-described technique can yield optimal collection of specimen for laboratory analysis.

Prior coordination with the laboratory can help to ensure optimal handling, processing, and analysis of the specimen. The undiluted specimen is sent for standard pathological stains, immunohistochemistry, cytokine analysis, and antibody levels, along with PCR testing if desired.23 Advances in PCR methods may improve the diagnostic sensitivity of PPV, and identify organisms previously not associated with intraocular inflammation.24,25 Gram stain, culture, and flow cytometry can be performed on the diluted vitreous sample.26 When considering diagnostic PPV, primary intraocular tumor, such as a uveal melanoma, should be excluded from the differential because inadvertent extrascleral extension of tumor cells has been reported from the sclerotomy sites.27 While chorioretinal biopsy was initially performed using a transscleral approach, PPV has gained favor due to its reduced risk of RD as well as vitreous and subretinal hemorrhage.28 Chorioretinal biopsy may be indicated when there is a disease process limited to the choroid and retina with minimal vitritis, and can be helpful in the identification or exclusion of intraocular malignancy. PPV should be performed, with separation of the posterior hyaloid at the site of biopsy. The superotemporal quadrant is preferred for chorioretinal biopsy as gas tamponade is more facile in this location for prevention of iatrogenic RD.29 Vertical scissors or a diamond blade are used to excise a 1-mm to 2-mm square portion of the suspicious retina and choroid after marking with diathermy. The specimen is removed through the ports, and endolaser barricade is applied around the biopsy site, followed by gas or oil for tamponade. Temporary elevation of the intraocular pressure to above 70 mmHg may help to minimize intraocular bleeding after excision of the specimen.30 In recent years, use of 25-gauge vitrectomy has been reported for successful chorioretinal biopsy.31

CONCLUSION

Vitrectomy represents a critical tool for the appropriate diagnosis of the underlying cause of intraocular inflammation, as well as a therapeutic option to restore vision for patients through removal of media opacity and restoration of retinal architecture. Use of smaller-gauge instrumentation allows for improvement on previous techniques of diagnosis. Inflammation should ideally be controlled prior to PPV in patients with uveitis. The multiple indications for vitrectomy in uveitis, heterogeneous nature of uveitis disease syndromes, and adjunctive therapies present challenges for clinical trials and are opportunities for further investigation. RP

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