The management of uveitis requires medical therapy and surgical intervention, when necessary. Surgical intervention is utilized to diagnose uveitic conditions, address uveitic conditions, and provide visual improvement. To provide a diagnosis, ocular fluid usually is sent for a multitude of analyses that assess for bacterial, fungal, and viral organisms as well as evaluate for the presence of vitreoretinal lymphoma. A few of the complications that can arise from uveitis include retinal detachment, hypotony, glaucoma, epiretinal membranes, and macular holes, each of which requires a specific surgical intervention.
Key points
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Uveitis can require surgical intervention for the diagnosis, treatment, and management of complications.
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Surgical outcomes in patients with uveitis can be complicated, require repeat interventions, and have a higher complication rate than routine ophthalmic surgery.
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Careful coordination is required between subspecialists when approaching these surgeries.
Introduction
The term uveitis encompasses multiple heterogeneous diseases with varied presentations. In general, uveitis is composed of noninfectious, infectious, and masquerade etiologies. Each of these carries with them a specific diagnostic and therapeutic approach. Surgical interventions can be instrumental in uveitis and serve multiple purposes. They can either help to elucidate a diagnosis, correct a complication of the disease, aid in therapy administration, or provide visual improvement. This review covers various surgical interventions in uveitis in each of these realms.
Significance
Diagnostic
The diagnosis of uveitis relies on a combination of pattern recognition, laboratory assessment, and history taking. Occasionally, obtaining ocular fluid can help make the diagnosis. In particular, ocular fluid analysis is helpful when the presentation is atypical, the disease worsens with corticosteroids, or a masquerade is suspected, such as vitreoretinal lymphoma ( Fig. 1 A, B ). Typical methods of retrieving fluid include an anterior chamber (AC) paracentesis, vitreous biopsy, and/or chorioretinal biopsy, depending on the level of suspicion and differential diagnosis [ , ].
Generally, an AC paracentesis is well tolerated with a minimal rate of complications [ ]. Extraction of the aqueous humor is done in the outpatient setting unless the patient is young and/or has a condition that prevents appropriate positioning or cooperation. In these rare circumstances, an AC paracentesis can be performed in the operating room under sedation. Typically, a 30 gauge (G) needle is attached to a tuberculin syringe, and inserted into the temporal or inferotemporal limbus. In phakic patients, extreme care is taken to avoid the lens; in all patients, careful placement of the needle is necessary to avoid iris incarceration. Monitoring the depth of the AC while collecting the sample is imperative to avoid excessive AC flattening [ ]. These AC humor samples can be sent for a variety of diagnostic tests, including a gram stain and culture, cytologic analysis, and polymerase chain reaction (PCR) for certain viral, bacterial, fungal, and acid-fast bacilli [ ]. Additionally, in cases where an organism cannot be isolated but infection is suspected, the sample can be sent for metagenomic deep sequencing (MDS), a process that theoretically allows for the detection of any pathogen by sequencing all the DNA and RNA in a sample [ ]. Outside of examining samples for possible pathogens, analysis of the aqueous fluid can provide an adjunct method of identifying lymphoma. The sample can be assessed for a mutation in myeloid differentiation primary response 88 (MYD88), which is commonly found in vitreoretinal lymphoma [ ]. However, it should be noted that a vitreous biopsy still is the main method of definitively assessing for vitreoretinal lymphoma.
Despite the utility of AC paracentesis, there are instances where a vitreous sample is needed. These include when a larger sample is needed for processing or when a vitreous sample provides a higher sensitivity for an organism as compared to the aqueous, such as in the case of toxoplasmosis [ ]. A small vitreous sample can be collected in clinic, usually through a 25G or 27G needle attached to a 1 or 3 CC syringe; however, care should be taken to avoid taking too much vitreous to avoid significant hypotony and choroidal formation. Additionally, there is a risk of retinal traction at the vitreous base with this procedure, leading to retinal tears and detachment. In certain cases, the hyaloid may be too formed to obtain a vitreous sample, at which point the approach can be converted to an AC paracentesis. The same diagnostic tests performed on an AC paracentesis can be performed on a vitreous sample. A vitreous sample obtained in the clinic may be sufficient for the analysis of infectious pathogens, but it is not the gold standard for the diagnosis of lymphoma.
In situations where the clinician suspects malignancy, they may require larger vitreous samples or vitreous debris precludes the view of the retina, a diagnostic vitrectomy may be utilized. Thankfully, advances in microincision vitrectomy have improved diagnostic yield as well as their overall safety, allowing for the collection of larger sample volumes with less retinal traction [ ]. A vitreous sample is typically obtained through a 3 port pars plana vitrectomy (PPV). It should be noted that in cases of uveitis, the choroidal thickening or an exudative detachment may exist; therefore, visualizing the tip of the infusion cannula in the vitreous cavity before proceeding with the surgery is imperative. Otherwise, a risk of creating a retinal detachment occurs if the infusion is caught under the retina.
The samples can be sent for numerous analyses, including, but not limited to, gram stain and culture, cytology, pathology, flow cytometry and immunohistochemistry, viral PCR, MDS, cytokine ratios, and ancillary lymphoma testing, such as MYD88. In particular, samples can be evaluated for their interleukin (IL)-10 to IL-6 ratio, with a ratio higher than 1 being linked to lymphoma [ ]. When obtaining the vitreous sample for vitreoretinal lymphoma, it can be helpful to first obtain an undiluted sample for cytologic analysis; further samples can be obtained with diluted samples [ ]. When obtaining an undiluted sample, it can be helpful to decrease the cut rate to increase cellular yield before the infusion is turned on. Typically, a syringe is attached to the vitrector and a core vitreous sample is collected with manual aspiration. The sample size usually is limited to 1 mL to avoid the formation of choroidals. An alternative to this technique involves collecting this undiluted sample under an air infusion, which maintains ocular pressure, but this can cause issues with the intraoperative view [ ]. It is also important to hold topical and oral steroids for at least 2 weeks before collecting a sample when a concern for lymphoma exists, as concomitant corticosteroid use can decrease the cellular yield. Additionally, communicating with the accepting laboratory is critical for the timely processing of samples to avoid cellular degradation [ , ].
In cases where retinal or choroidal lymphoma is suspected, a fine-needle biopsy of these areas can be done through a transscleral or transvitreal approach. Typically, this is done with a 25 G needle attached to tubing and a syringe. A direct retinal or subretinal biopsy also can be done under visualization with vitrectomy instruments. This requires a vitrectomy to remove the overlying vitreous and debris that can be sent for testing and a retinal hole or flap, through which the subretinal or choroidal material is accessed. Rarely, an external chorioretinal biopsy is required, which can require access through a scleral flap. These procedures are not without risks and can lead to significant complications, including intraocular hemorrhage, proliferative vitreoretinopathy (PVR), and retinal detachment [ ].
In cases where the view is precluded from vitreous hemorrhage or inflammation, removal of the vitreous for testing also allows for the inspection of the retina, monitoring response to therapies, and can be visually therapeutic ( Fig. 2 A, B ) [ ]. As compared to cataract surgery, where 3 months of quiescence is recommended, vitrectomy for intermediate and posterior uveitis can be performed and effective in the setting of active inflammation or incomplete intraocular inflammation control [ ].
Addressing complications
Cystoid macular edema
Cystoid macular edema (CME) is one of the most common complications from uveitis and a major cause of vision loss [ ]. Speculation exists that cytokines and chemokines released during an inflammatory episode contribute to vascular leakage yielding CME. Additionally, CME can be related to tangential and contractual forces from the overlying hyaloid face and internal limiting membrane.
In both of these cases, the removal of inflammatory debris and traction has been said to decrease CME formation and prevent its recurrence. One study showed a reduction in CME formation in uveitic eyes from 36% to 18% after PPV [ ]. In another retrospective study of 23 patients, 87.5% had improvement in CME after vitrectomy at 12 months, with 77.8% showing an improvement in vision, 62.5% showing a reduction in inflammation, and 26% experienced a reduction in their need for steroids or immunosuppression [ ]. Additionally, other studies have shown improvement in CME with vitrectomy, internal limiting membrane peel, and local steroid therapy [ ]. Further research is warranted to understand whether this surgical intervention provides a better outcome than traditional medical therapy.
Retinal detachment
Retinal detachment may occur in the setting of uveitis as a direct consequence of the inflammation or infection (ie, in the setting of infectious retinitis with the generation of multiple retinal holes, or contraction of the vitreous). They also can be unrelated but become more complicated from the overlying inflammation. Retinal detachments in uveitis still fall into the same general categories of rhegmatogenous, tractional, or exudative. While the same three main categories of detachments exist, uveitic retinal detachments do carry with them a specific set of considerations. A significant complicating factor includes the overlying inflammation, which can interfere with retinal visualization, making it difficult to assess the morphology of the detachment and the extent of its pathology. Additionally, inflammation may persist after the retinal detachment repair which can limit visualization of the retina and increase the patient’s risk of developing PVR, cyclitic membranes, hypotony, and glaucoma.
Prior studies have noted an increased rate of rhegmatogenous retinal detachment in uveitic conditions, with rates between 2% and 3% in noninfectious uveitis and much higher in certain types of infectious uveitis [ ]. Unfortunately, the rates of success of retinal detachment repair are lower in these patients, around 60% [ ]. Moreover, the rates of postoperative PVR are high in patients with uveitis, with one study citing a rate of 37% [ ]. Assessing if a retinal detachment is rhegmatogenous can be difficult; the holes in the detachment usually occur peripherally at sites of vitreoretinal traction and can be numerous and small, making them difficult to identify. If a retinal hole is not identified, the concern occurs that the detachment is exudative as a result of the intraocular inflammation. If it is unclear whether a retinal detachment is rhegmatogenous or exudative, it can be helpful to give the patient a trial of oral steroids in cases of noninfectious uveitis (typically 1 mg/kg/day) for a few weeks to see if improvement occurs in the fluid. If the fluid does not improve, it makes the possibility of rhegmatogenous detachment more likely. These patients warrant a vitrectomy with surgical repair, with an option of a scleral buckle depending on the site of pathology.
When specifically assessing infectious retinitis, rhegmatogenous detachments occur at an even higher rate. There have been varying reports in the literature on the utility of prophylactic laser barricade before a retinal detachment occurs, or prophylactic vitrectomy to relieve vitreous traction, but the results are mixed [ , ]. In the case of an infectious retinitis-related detachment, the typical surgical intervention consists of vitrectomy combined with membrane peeling, if applicable, possible scleral buckle and silicone oil placement. This approach provides anatomic success in over 50% of patients, but repeat surgery is common ( Fig. 3 ) [ , ]. Moreover, there is no consensus on the best surgical intervention for these complicated cases, and further research is required in this realm. Visual prognosis in these patients is limited, given optic nerve ischemia, PVR, and multiple atrophic holes. Reports exist that have shown improved surgical outcomes in patients treated with antiviral and steroid medications before surgery and a prolonged period between the onset of infectious retinitis and detachment [ ].
