Vitreoretinal Surgery In Inflamed Eyes

What to do when inflammation can no longer be treated nonsurgically

ROYCE W. S. CHEN, MD • JANET L. DAVIS, MD

Similar to any other intraocular surgery, vitreoretinal surgery in inflamed eyes is not desirable but may be unavoidable. A classic example would be an exogenous or endogenous endophthalmitis that cannot be managed with vitreous aspiration and injection of antibiotics.

Vitreoretinal complications, such as retinal tears or breaks in such eyes, can be blinding. Less extreme degrees of inflammation may still expose the patient to greater than normal risks from surgery. These include worse results if surgical complications occur, further damage to already impaired tissue in the macula, and worsened inflammation or new uveitic complications.

Controlling the inflammation meticulously before surgery, as recommended for cataract surgery, is usually not possible unless the surgeon performs vitrectomy solely to clear visually significant vitreous opacities in an eye that is either postinflammatory or that has well-controlled uveitis.

In many cases, however, surgery is either necessary to correct some urgent problem or for diagnostic purposes to obtain material from eyes with active inflammation so the patient can receive effective treatment. Treatment can paradoxically reduce the ability to diagnose in difficult cases by masking signs of disease.

INDICATIONS FOR URGENT VITRECTOMY

Retinal detachment may occur in inflamed eyes from vitreoretinal traction or the formation of retinal breaks. Peripheral retinal complications are most likely to occur in eyes with intermediate uveitis and significant peripheral, inferior traction.

Often the surgeon will encounter epiretinal membranes that cover the entire retinal surface and are tightly adherent. Relief of all traction or membranes may not be possible, and the formation of new breaks can change the prognosis. Detachment can occur during elective vitrectomies in pars planitis.

Surgeons can address spontaneous retinal breaks from vitreous contraction at the healed border of confluent disseminated chorioretinitis with peeling to the border, endolaser posterior to the border, and silicone oil instillation.

Controversy exists as to whether early surgery in acute retinal necrosis (ARN) is warranted to reduce the risk of detachment.¹ Laser demarcation may reduce the risk of detachment and consequently improve visual prognosis.

Eyes that have persistently poor media and that cannot undergo laser are candidates for early vitrectomy surgery, with the understanding that the inflammation is likely still active. Silicone oil will help to stabilize the retina but usually does not stop ERM growth in an eye that is still inflamed.

A typical sequence of surgery would be as follows:

• identify eyes that are healing but are not sufficiently clear for laser despite treatment with antivirals and oral prednisone;

• perform vitrectomy with membrane peeling, and apply demarcating laser with silicone oil tamponade, as well as periocular triamcinolone acetonide; and

• remove the oil (and usually the cataract) at three months when the inflammation has subsided, and repeel recurrent membranes and relaser as needed, with a short-acting gas tamponade.

Other Urgent Indications

In some cases of ARN and CMVR, the surgeon may achieve disease quiescence, yet retinal detachments still occur. Whereas ARN detachments can dramatically alter prognosis, CMVR produces much less inflammation, fewer membranes, and less hypotony and globe loss than ARN, even with total retinal detachment.

The visual prognosis may be excellent in CMVR-related detachment initially if it does not involve the posterior pole, but long-term retinal detachment is a common cause of vision loss in CMVR.^2,3

Late complications of healed chorioretinitis, particularly CMVR, include the subsequent formation of dense fibrosis with chorioretinal neovascularization. This tissue contracts in some patients, causing tractional detachments that are difficult to manage, even with silicone oil.

INDICATIONS FOR NONURGENT VITRECTOMY

Diamond and Kaplan initially reported on pars plana vitrectomy as a therapy for the management of complicated uveitic cataracts with pars plana lensectomy. It remains an option for severe disease.⁴

A previous review of 44 interventional case series published over a 25-year period from 1981 to 2005 found that of 1,762 total eyes with uveitis treated with vitrectomy, vision improved in 70% of cases, remained stable in 14%, and worsened in 9%.⁵

The most common condition treated was intermediate uveitis, and cataract and cystoid macular edema were common comorbidities. The median reported percentage of patients per study with CME was 36% preoperatively and 18% postoperatively. Pediatric uveitis cases appeared to respond especially well to PPV.⁶

More recently, two randomized, controlled pilot studies evaluated the effects of PPV in chronic uveitis.^7,8 Although neither study was adequately powered to show a statistically significant benefit, a greater percentage of patients in the PPV arms showed improvement in uveitis or benefit in visual function compared to those treated with immunomodulatory therapy alone. Furthermore, it seemed PPV could decrease the need for immunomodulatory therapies.⁸

Because of these favorable reports, surgeons frequently subject eyes with intermediate uveitis to elective vitrectomy to clear the media and to attempt to downregulate the activity of the uveitis (Figure 1).^8,9

Figure 1. A 16-year-old male patient with intermediate uveitis was treated with methotrexate prior to surgery. Pars plana vitrectomy cleared symptomatic vitreous opacities and improved his VA. A and B) Preoperative fluorescein angiography demonstrating diffuse capillary leakage and vitreous opacities causing patches of hypofluorescence. C and D) After vitrectomy, the shadowing opacities are cleared, and capillary leakage is significantly reduced, suggesting a disease-modifying effect of PPV.

The surgeon should avoid as sclerotomy sites stiff extraretinal membranes that cover the pars plana. This tissue cannot be lasered, and holes will not close. Contraction can pull the peripheral membranes away from the eye wall and cause a chronic detachment.

Strategies to avoid these complications include placement of all sclerotomies superiorly, where membranes are less likely to occur, careful examination of the pars plana prior to making sclerotomies, and use of ultrasound or endoscopy to check for membranes in eyes that have poor visibility.

Tight adhesions of hyaloid or preretinal membrane to thin retina at and anterior to the equator in intermediate uveitis can also lead to retinal holes with aggressive peeling.

Conservative dissection, confined to the area posterior to the equator, is usually preferable, especially with adherent membranes. Informed consent and a prepared surgeon are necessary before attempting vitrectomy in any eye with peripheral membranes and intermediate uveitis.

Further Considerations

Studies have described ERM peeling for CME mainly as a surgical strategy to improve DME, but early reports usually also included cases of uveitic macular edema.^10,11 The main concern in uveitic eyes is that concomitant damage from long-standing macular edema may exist, which can result in poor visual results.

One of four uveitis patients reported by Cho and D’Amico had improved vision; the authors treated none of these patients preoperatively with corticosteroids.¹² The surgeon should consider identification of inflammatory macular leakage or active uveitis and meticulous medical control before attempting elective ERM peeling to improve vision (Figure 2).

Figure 2. A 50-year-old woman with uveitis and vitreomacular traction. She was treated with methotrexate over a three-year period but experienced increasing CME and VMT. Combined vitrectomy surgery with implantation of a fluocinolone acetonide drug delivery device and membrane peeling led to recovery of normal foveal contour and resolution of central macular leakage. A) Preoperative fluorescein angiography showing CME, disc, and capillary leakage. B) Preoperative OCT with macular cysts, VMT, and nasal subretinal fluid. C) Postoperative fluorescein with reduced CME and peripheral leakage. D) Postoperative OCT with restored foveal contour and resolved VMT.

Hypotonous eyes are a separate category of uveitic eyes that may benefit from PPV. Previous immunomodulatory therapy might have controlled inflammation. However, visual deterioration and globe shrinkage may have occurred due to hypotony. These eyes are characterized by heavy flare in the anterior chamber.

Although some patients with more rigid sclera may be able to tolerate hypotony, in most others with severe hypotony, with IOP often reaching 0 mm Hg, inexorable decline in visual function occurs.

In these eyes, PPV with instillation of silicone oil can preserve an IOP of approximately 5 mm Hg. This procedure can preserve ambulatory vision in patients with advanced disease.

However, over time, the IOP tends to decrease, and oil emulsification and corneal opacification/band keratopathy remain long-term complications. Surgery to place a permanent keratoprosthesis and either supplement or instill silicone oil facilitates rehabilitation of previously unsalvageable eyes.^13-15

The following principles apply to elective, therapeutic PPV for uveitis.

First, if possible, establish medical control of inflammation with a stable regimen of immunosuppressive medications or long-duration corticosteroids prior to surgical intervention.

Second, although VA often improves following PPV, the surgeon should not mistake the clarity of ocular media for control of uveitis. It remains controversial whether removal of the vitreous helps to control uveitis, as well as which patients are the best candidates.

Third, in patients who require intravitreal therapy, the surgeon should weigh the benefits of vitrectomy against the possible disadvantage that removal of the vitreous may allow for increased clearance of intravitreally administered drugs.

Finally, factors predictive of surgical success for uveitic macular edema are unknown, but they are likely intertwined with prior structural damage and control of inflammation.

INDICATIONS FOR DIAGNOSTIC VITRECTOMY AND CHORIORETINAL BIOPSY

Even in eyes with possible infectious uveitis, more conservative diagnostic steps are usually recommended first, such as syphilis serology, and in the case of chorioretinitis, anterior-chamber paracentesis for herpesviruses.^16,17

In general, the surgeon should consider for diagnostic vitrectomy eyes with presumed infectious uveitis that has not been diagnosed satisfactorily or that has not responded to empiric treatment within 10-14 days, to allow for additional sampling and to better visualize the fundus.

Suspected intraocular lymphoma, diagnosed by the ophthalmologist, often has no CNS involvement initially; the physician might consider preoperative MRI of the brain with FLAIR and gadolinium contrast, but it is not mandatory.

Confirming intraocular lymphoma by vitrectomy will usually suffice for diagnosis, even if brain lesions are present. Multiple samples and analyses are recommended in any unknown case.

Our Approach

We typically use a 23-gauge vitrectomy system with a standard three-port approach. Twenty-five–gauge PPV also provides adequate cellular yield for the diagnosis of lymphoma.¹⁸

Following creation of the sclerotomies and securing of the unopened infusion line, we remove an undiluted vitreous specimen with the vitrectomy handpiece and aspirate manually into an inline 3-cc syringe until we observe the eye visibly soften. (Some vitrectomy machines may require closure of the aspiration line with a hemostat.) Reports have demonstrated no significant difference in cell viability based on cut rates or method of aspiration.^19,20

We then open the infusion, remove the handpiece from the eye, and aspirate the residual vitreous into the syringe. The specimen is considered pure vitreous and is suitable for cytology or quantitative PCR or antibody determinations.

With the infusion open, we cut the vitreous and manually aspirate it into a 20-mL syringe. Both this specimen and the vitreous wash in the machine cassette are suitable for bacterial and fungal culture and flow cytometry.

Chorioretinal Biopsy

Chorioretinal biopsy is a choice when previous diagnostic PPV has been inconclusive, or the vitreous cellular reaction is too small to expect a positive result without histology.

Usually, high suspicion exists of lymphoma or an infection that involves the retina or subretinal space. The surgeon can perform aspiration of abscesses that form at the level of the RPE, such as nocardia, or of the solid sub-RPE detachments created by proliferating lymphoma cells through a small slit made with a sharp blade over the dome of the deposit.

An assistant attaches a silicone-tip needle to a 3-cc syringe with manual aspiration or to an inline 3-cc syringe with foot pedal control in very low vacuum extrusion mode.

Fine needle aspiration biopsy (FNAB), performed ab externo or interno, is an alternative for nonlymphoid tumors because only a few cells need to be identified to diagnose melanoma or metastatic disease.

Lymphoid proliferations and infections usually require a larger specimen than FNAB can provide. Consultation with a pathologist is recommended before obtaining specimens for histology, but in general, the tissue is placed in formalin.

A convenient technique for chorioretinal biopsy is to remove hyaloid completely, demarcate the biopsy site with endolaser, make a separate 20-gauge sclerotomy, cut a rectangular section of retina with vertical 20-gauge scissors on a Grieshaber handle, and diathermize blood vessels as needed. The biopsy is usually left attached by a strand to the retina to prevent loss.

The surgeon can use an 18-gauge blunt fill needle without filter to manually aspirate the specimen into a 10-cc syringe. A direct line of sight to the specimen at all times is important, both as it enters the needle and as it enters the syringe barrel.

Removing the syringe plunger and pouring the specimen into a sterile petri dish facilitates identification and retrieval for transfer into formalin. Specimens at least 3 mm (2 disc widths) in dimension are easy to see and handle.

We advise hand delivery to the pathology lab to prevent loss of the specimen container by personnel who may not recognize the small fragment of tissue as a histology specimen.

Choroidal biopsies are taken as a separate step. If the tissue is truly infiltrated, little bleeding should occur, but temporary elevation of eye pressure and diathermy are effective strategies to control any bleeding. Air or gas tamponade at the end of the case is adequate to prevent retinal detachment in most cases.

SUMMARY

Vitreoretinal surgery plays a vital role in the management of the most challenging uveitis cases, including those with sight-threatening disease from infection or retinal detachment. In appropriate patients, elective therapeutic vitrectomies can improve visual acuity and may decrease the reliance on systemic immunomodulatory agents.

Diagnostic vitrectomy, including chorioretinal biopsy, can often lead to a diagnosis when all other avenues have failed. Selection of proper patients, biopsy sites, and specimen analyses will maximize diagnostic yield. RP

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