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

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

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.

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

REFERENCES

1. Becker M, Davis J. Vitrectomy in the treatment of uveitis. Am J Ophthalmol. 2005;140(6):1096-1105.
2. Vitale AT. Vitrectomy in Patients with Uveitis. Rev Ophthalmol. 2006 Mar. Available at https://www.reviewofophthalmology.com/article/vitrectomy-in-patients-with-uveitis .
3. Tanawade RG, Tsierkezou L, Bindra MS, et al. Visual outcomes of pars plana vitrectomy with epiretinal membrane peel in patients with uveitis. Retina. 2015;35(4):736-741.
4. Kiryu J, Kita M, Tanabe T, Yamashiro K, Miyamoto N, Ieki Y. Pars plana vitrectomy for cystoid macular edema secondary to sarcoid uveitis. Ophthalmology. 2001;108(6):1140-1144.
5. Dev S, Mieler WF, Pulido JS, Mittra RA. Visual outcomes after pars plana vitrectomy for epiretinal membranes associated with pars planitis. Ophthalmology. 1999;106(6):1086-1090.
6. Branson SV, McClafferty BR, Kurup SK. Vitrectomy for epiretinal membranes and macular holes in uveitis patients. J Ocul Pharmacol Ther. 2017;33(4):298-303.
7. Khalil HEDM, Gendy HAE, Raafat HA, Haroun HE, Gheita TA, Bakir HM. The effectiveness of pre- and postoperative infliximab in controlling behçet’s disease posterior uveitis in patients undergoing vitrectomy: a preliminary study. J Ophthalmol. Epub 2017 Apr 4.
8. Ryan ME, Shantha JG, Grossniklaus HE, Yeh S. Secondary vitreoretinal lymphoma masquerading as acute retinal necrosis. Ophthalmic Surg Lasers Imaging Retina. 2015;46(10):1048-1050.
9. Thomas AS, Flaxel CJ. Vitreoretinal surgery in uveitis. Int Ophthalmol Clin. 2015;55(2):67-79.
10. Coupland SE, Bechrakis NE, Anastassiou G, et al. Evaluation of vitrectomy specimens and chorioretinal biopsies in the diagnosis of primary intraocular lymphoma in patients with Masquerade syndrome. Graefes Arch Clin Exp Ophthalmol. 2003;241:860-870.
11. Yeh S, Weichel ED, Faia LJ, et al. 25-gauge transconjunctival sutureless vitrectomy for the diagnosis of intraocular lymphoma. Br J Ophthalmol. 2010;94(5):633-638.
12. Butler NJ, Moradi A, Salek SS, et al. Acute retinal necrosis: presenting characteristics and clinical outcomes in a cohort of polymerase chain reaction-positive patients. Am J Ophthalmol. 2017;179:179-189.
13. Faridi A, Yeh S, Suhler EB, Smith JR, Flaxel CJ. Retinal detachment associated with ocular toxoplasmosis. Retina. 2015;35(2):358-363.
14. Yeh S, Suhler EB, Smith JR, et al. Combination systemic and intravitreal antiviral therapy in the management of acute retinal necrosis syndrome. Ophthalmic Surg Lasers Imaging Retina. 2014;45(5):399-407.
15. Hillenkamp J, Nölle B, Bruns C, Rautenberg P, Fickenscher H, Roider J. Acute retinal necrosis: clinical features, early vitrectomy, and outcomes. Ophthalmology. 2009;116(10):1971-1975.
16. Huang JM, Callanan P, Callanan D, Wang RC. Rate of retinal detachment after early prophylactic vitrectomy for acute retinal necrosis. Ocul Immunol Inflamm. 2016;11:1-4.
17. Lau CH, Missotten T, Salzmann J, Lightman SL. Acute retinal necrosis features, management, and outcomes. Ophthalmology. 2007;114(4):756-762.
18. Luo YH, Duan XC, Chen BH, Tang LS, Guo XJ. Efficacy and necessity of prophylactic vitrectomy for acute retinal necrosis syndrome. Int J Ophthalmol. 2012;5(4):482-487.
19. Almeida DR, Chin EK, Tarantola RM, et al. Long-term outcomes in patients undergoing vitrectomy for retinal detachment due to viral retinitis. Clin Ophthalmol. 2015;16;9:1307-1314.
20. Kopplin LJ, Thomas AS, Cramer S, et al. Long-term surgical outcomes of retinal detachment associated with acute retinal necrosis. Ophthalmic Surg Lasers Imaging Retina. 2016;47(7):660-664.
21. Jeroudi A, Yeh S. Diagnostic vitrectomy for infectious uveitis. Int Ophthalmol Clin. 2014;54(2):173-197.
22. Margolis R, Brasil OF, Lowder CY, et al. Vitrectomy for the diagnosis and management of uveitis of unknown cause. Ophthalmology. 2007;114(10):1893-1897.
23. Davis JL, Miller DM, Ruiz P. Diagnostic testing of vitrectomy specimens. Am J Ophthalmol. 2005;140(5):822-829.
24. Hong BK, Lee CS, Van Gelder RN, Garg SJ. Emerging techniques for pathogen discovery in endophthalmitis. Curr Opin Ophthalmol. 2015;26(3):221-225.
25. Lee AY, Akileswaran L, Tibbetts MD, Garg SJ, Van Gelder RN. Identification of torque teno virus in culture-negative endophthalmitis by representational deep DNA sequencing. Ophthalmology. 2015;122(3):524-530.
26. Zaldivar RA, Martin DF, Holden JT, et al. Primary intraocular lymphoma: clinical, cytologic, and flow cytometric analysis. Ophthalmology. 2004;111(9):1762-1767.
27. Kavanagh MC, Everman KR, Opremcak EM, Foster JA. Uveal melanoma with massive extrascleral extension via pars plana vitrectomy sites. Ophthal Plast Reconstr Surg. 2008;24(4):334-336.
28. Lim LL, Suhler EB, Rosenbaum JT, Wilson DJ. The role of choroidal and retinal biopsies in the diagnosis and management of atypical presentations of uveitis. Trans Am Ophthalmol Soc. 2005;103:84-92.
29. Johnston RL, Tufail A, Lightman S, et al. Retinal and choroidal biopsies are helpful in unclear uveitis of suspected infectious or malignant origin. Ophthalmology. 2004;111(3):522-528.
30. Cole CJ, Kwan AS, Laidlaw DA, Aylward GW. A new technique of combined retinal and choroidal biopsy. Br J Ophthalmol. 2008;92(10):1357-1360.
31. Bagger M, Tebering JF, Kiilgaard JF. The ocular consequences and applicability of minimally invasive 25-gauge transvitreal retinochoroidal biopsy. Ophthalmology. 2013;120(12):2565-2572.