Persistent Inflammation Associated With HLA-B27 After Pars Plana Vitrectomy With Scleral Buckle Placement

Abstract

Purpose: To report 2 cases of persistent inflammation associated with human leukocyte antigen-B27 (HLA-B27) after pars plana vitrectomy (PPV) with scleral buckling. Methods: Two cases were analyzed. Results: A 47-year-old man had pars plana vitrectomy (PPV), scleral buckle (SB) placement, and endolaser for a macula-on rhegmatogenous retinal detachment (RRD). A 61-year-old man also had uneventful PPV, SB placement, and endolaser for a macula-off RRD. Postoperatively, both patients reported eye pain and had persistent intraocular inflammation. Both were found to be HLA-B27 positive despite having no previous signs or symptoms that would warrant HLA-B27 testing. Conclusions: Discovering the source of prolonged postoperative inflammation is critical in initiating the correct treatment and removing suspicion of infection. Although intraocular inflammation associated with HLA-B27 does not often present initially after surgery, HLA-B27 testing should be considered in cases of persistent, unexpected postoperative inflammation.

Introduction

Mild acute inflammation after intraocular surgery is common, and it has been shown that management of postoperative inflammation can improve outcomes.^{1 –3} Modern vitreoretinal surgical techniques, which use smaller gauge systems, have reduced the rates of postoperative inflammation.^4,5 Vitrectomies and scleral buckle (SB) placement typically do not cause significant complications.^{6 –11}

Human leukocyte antigen-B27 (HLA-B27) is a major histocompatibility complex (MHC) class I molecule that is associated with a wide range of inflammatory diseases, including uveitis.^{12 –15} Clinical manifestations of HLA-B27 uveitis vary depending on which area of the uveal tract is inflamed. Anterior uveitis is most common and can present with redness, pain, and swelling. ¹⁶ In contrast, patients with intermediate and posterior uveitis often present with reduced visual acuity (VA), floaters, or other abnormal vision changes.

The associations between HLA-B27 and uveitis, especially anterior uveitis, are well established in the literature.^17,18 Although less common, posterior uveitis associated with HLA-B27 has also been described, which if left untreated has a greater risk for leading to permanent vision loss.^{19 –21} Some authors suggest an existing association between retinal detachment (RD) and patients who are HLA-B27 positive.^18,22,23 However, to our knowledge there are no previous reports of HLA-B27 positivity associated primarily with postoperative inflammation.

Here, we present 2 patients with no known history of uveitis who developed worsening, prolonged postoperative inflammation after pars plana vitrectomy (PPV) with SB placement and were found to be HLA-B27 positive.

Case Reports

Case 1

A 47-year-old man presented to the emergency department with 1 week of floaters, a new curtain in his temporal visual field, and blurry vision in the right eye. His medical history included hypertension, hypercholesterolemia, and gout. His ocular history consisted of cataract surgery 3 years previously, neodymium:YAG laser capsulotomy, and high myopia with lattice degeneration in both eyes but was negative for previous ocular inflammation. He had a family history of RD (his mother and his uncle). On presentation, the uncorrected VA was 20/25 OD and 20/70 OS. An anterior segment examination was unremarkable. A fundoscopic examination showed a nasal macula-on rhegmatogenous RD (RRD), large patches of posterior lattice degeneration, superior and inferior tears, and multiple atrophic holes in the right eye (Figure 1, A and B). No preoperative inflammation was noted.

Figure 1.

Fundus and slitlamp photographs of Case 1. (A and B) Fundus photograph shows nasal macula-on rhegmatogenous retinal detachment, large patches of posterior lattice degeneration, superior and inferior tears, and multiple atrophic holes in the right eye. (C) Slitlamp photograph shows conjunctival injection postoperatively. (D) Slitlamp photograph of inferior keratic precipitates.

The patient had PPV, SB placement, retinotomy, endolaser, and injection of 17% perfluoropropane (C₃F₈) gas in the right eye without complications. Intraoperatively, an additional, separate superotemporal RD was seen and treated. At the end of surgery, the patient received a sub-Tenon injection of triamcinolone and a subconjunctival injection of cefazolin and dexamethasone.

Examination on postoperative day 1 was notable for hand motions VA and an intraocular pressure (IOP) of 24 mm Hg in the right eye with an attached retina. The patient was started on a standard regimen of moxifloxacin (1 drop 4 times a day), prednisolone acetate 1% (1 drop 4 times a day), and atropine 1% (1 drop daily) in the right eye.

One week postoperatively, the patient presented to the emergency department with periorbital swelling of the right eye that was considered to be significantly greater than what would be expected after SB placement as well as an associated headache requiring acetaminophen. The VA in the right eye was counting fingers at 2 ft. A slitlamp examination showed periorbital edema without erythema, a subconjunctival hemorrhage, significant conjunctival chemosis, and 90% gas in the vitreous chamber. There was no cell or flare in the anterior chamber (AC). The patient was started on ibuprofen 400 mg 4 times a day and given a methylprednisolone dose pack for the orbital swelling.

Three days later, the IOP increased to 38 mm Hg in the right eye, which was thought to be the result of a possible steroid response. The patient was tapered off the prednisolone acetate eyedrops. The moxifloxacin and atropine 1% eyedrops were also discontinued. He was started on dorzolamide–timolol 22.3–6.8 mg/mL (1 drop twice a day), brimonidine (1 drop 3 times a day), and acetazolamide 500 mg extended-release twice daily. Two weeks later, he continued to have a headache with pain around the right eye; however, the IOP had normalized. The acetazolamide was discontinued, and the patient was started on ketorolac 0.5% (1 drop 4 times a day).

Three weeks postoperatively, the patient again presented to the emergency department with eye pain. The VA was 20/300 and the IOP 14 mm Hg in the right eye. An examination showed periorbital edema with mild edema, 2+ conjunctival injection (Figure 1C), new 2+ AC cell and flare, trace corneal edema, inferior keratic precipitates (Figure 1D), and diffuse fibrin on the corneal endothelium. On fundus examination, the retina was attached. The patient’s presentation was thought to be consistent with intraocular and periocular inflammation, and he was treated with indomethacin 50 mg 3 times daily. The patient was continued on the ketorolac, dorzolamide–timolol, and brimonidine eyedrops.

Because of the persistent eye pain and inflammation, computed tomography of the orbit was performed, which showed mild preseptal inflammatory changes with no evidence of abscess formation. An iris angiogram showed no evidence of ischemia or abnormal vessels. In addition, an AC paracentesis was performed and a uveitis workup was sent. There was concern that some of the inflammation was rebound inflammation after steroid cessation, and the patient was restarted on prednisolone acetate (1 drop 4 times daily) and atropine (1 drop daily) in the right eye, with significant improvement in the symptoms. The uveitis workup ultimately showed HLA-B27 positivity. The swelling slowly improved, resolving between week 3 and week 4.

Case 2

A 61-year-old man presented to the emergency department with 1 week of new floaters, a shadow in his superior visual field, and blurry vision in the right eye. His medical history included hypercholesterolemia and gout. His ocular history was significant only for myopia in both eyes. He had no history of intraocular surgery. On presentation, the best-corrected VA (BCVA) was 20/60 OD and 20/25 OS. The anterior segment examination was unremarkable. A fundoscopic examination showed a macula-off RRD resulting from a single horseshoe tear with early proliferative vitreoretinopathy in the right eye. There was no evidence of intraocular inflammation.

The patient had PPV, placement of scleral buckle, retinotomy, endolaser, and injection of 16% C₃F₈ gas in the right eye, without complications. At the end of surgery, the patient received a sub-Tenon injection of triamcinolone and a subconjunctival injection of cefazolin and dexamethasone.

On postoperative day 1, the patient reported mild pain requiring acetaminophen. The VA was hand motions and the IOP was 27 mm Hg in the right eye. On slitlamp examination, mild subconjunctival hemorrhage, trace corneal edema, and a small hyphema (<1 mm) were noted. There were no cells in the AC or the vitreous. The retina was attached. He was started on a moxifloxacin (1 drop 4 times a day), prednisolone acetate 1% (1 drop 4 times a day), atropine 1% (1 drop daily), and dorzolamide–timolol 22.3–6.8 mg/mL (1 drop twice a day) in the right eye.

On postoperative day 4, the patient continued to have pain and reported headaches with occasional tearing of the right eye. The IOP was 40 mm Hg and a mild increase in hyphema (1.5 mm) was noted in the right eye. The moxifloxacin drops were discontinued, and brimonidine 0.2% (1 drop 3 times a day) was added to the above regimen.

The patient was followed closely. Despite these interventions, the patient’s IOP remained elevated to 36 mm Hg 1 week after surgery. At that time, the eye pain had become severe, and his headache had worsened. There was a decrease in the hyphema (1 mm). The atropine was increased to twice daily. Latanoprost (1 drop nightly), acetazolamide extended-release 500 mg twice daily, and ibuprofen 600 mg 3 times a day were added and the brimonidine was stopped because of a concern for corneal toxicity. For the severe pain, the patient was prescribed hydrocodone–acetaminophen as needed.

By 2 weeks postoperatively, the patient’s pain had improved significantly. The BCVA had improved to 20/70 and the IOP had normalized to 21 mm Hg in the right eye. A slitlamp examination showed injection (Figure 2A), corneal striae, and worsening 3+ to 4+ pigmented anterior cells. Fifty percent of the gas was left in the eye. A fundus examination showed an attached retina superiorly; however, there was significant vitreous haze with a poor view inferiorly (Figure 2B). B-scan ultrasonography showed an attached retina and mild inflammation. Based on these findings, the prednisolone acetate 1% was increased to 1 drop every 2 hours with a subsequent improvement in pain.

Figure 2.

Slitlamp and fundus photograph of patient Case 2. (A) Slitlamp photograph shows significant conjunctival injection. (B) Fundus photograph shows vitreous haze 1 month postoperatively.

One month later, the patient’s VA improved to 20/60 and his IOP improved to 12 mm Hg in the right eye. A laboratory workup found that the patient was HLA-B27 positive. The atropine and IOP-lowering eyedrops were discontinued, and the prednisolone acetate 1% was tapered.

At the 4-month follow-up visit, the patient’s BCVA was 20/40 and the IOP remained normal. The AC was clear and quiet, and the retina was attached. At this time, the patient was off all medications.

Conclusions

We present what to our knowledge is the first report of postoperative inflammation associated with HLA-B27. The 2 patients developed persistent pain with headache after RD repair. Of note, the inflammation peak occurred weeks after the initial surgery.

HLA-B27 and its association with inflammatory diseases is the most extensively studied relationship between an MHC and disease. ²⁴ The pathophysiologic process by which HLA-B27 causes uveitis and other inflammatory diseases is not fully elucidated in humans. Several hypotheses have been proposed and studied in animal models, including antigen-dependent and antigen-independent pathways; however, research in humans is insufficient.^{12,25 –32} Despite the level of resources dedicated to this area of research, there is an absence in the literature regarding postoperative vitreoretinal surgery inflammation in patients who are HLA-B27 positive. One case report described postoperative inflammation after cataract surgery; however, this patient had been diagnosed with ankylosing spondylitis and anterior uveitis before surgery. ³³ In our cases, neither patient had a known history of uveitis, ankylosing spondylitis, or HLA-B27 positivity preoperatively.

Some patients may be prone to increased inflammation after vitrectomy. On removal of the vitreous humor, macrophages and neutrophils along with their inflammatory cytokines can easily reach the posterior chamber of the eye from the iris and AC. ⁶ Patients with high levels of inflammatory mediators or cytokines may be particularly at risk for postoperative inflammation, especially those with diabetes. ³⁴ Toxicity to silicone oil (SO) can also be a culprit in postoperative inflammation ³⁵ ; however, SO was not used in our patients. The findings that were not expected in the routine postoperative course in this series were the persistent worsening 2 to 3 weeks after surgery, keratic precipitates, and vitreous haze, all despite topical and systemic antiinflammatory treatment.

This principle of HLA-B27 being associated with postoperative inflammation may be applicable to other forms of intraocular surgery. There was some value in uncovering the HLA-B27 association and performing the uveitis workup after surgery. The primary concern is often for infectious etiologies when these symptoms and signs are present in the postoperative period. Suspicion for postoperative endophthalmitis can lead to invasive diagnostics. However, once an inflammatory cause is determined, systemic and topical anti-inflammatory medication can be increased with less hesitation. If the patient is found to be HLA-B27 positive, oral nonsteroidal antiinflammatory drugs can be added in addition to topical steroids. ³² Occasionally, oral steroids may be needed for severe cases. ³⁶ Recently the use of biologic agents, specifically antitumor necrosis factor-alpha, have been used with positive outcomes, such as reduced inflammation and decreased occurrences of uveitis flares^{37 –41}; however, such agents were not required in our cases. This is in contrast with cases of posterior uveitis associated with HLA-B27 unrelated to surgery, which are often chronic and require systemic immunosuppression. ²¹

A limitation of this report is that the association of HLA-B27 with postoperative inflammation does not prove causality. Of note, the rate of HLA-B27 positivity in the general population ranges from 3.5% to 7.5%, with an approximate rate of 3.6% for adults 50 to 69 years of age. ⁴² Larger studies based on this report are required to conclusively make this determination. In addition, AC paracentesis with measurement of proinflammatory cytokines in patients with and without HLA-B27 positivity could help prove a causal association.

In summary, HLA-B27 positivity was found in association with unexpected, delayed, and progressive intraocular inflammation after RD repair. Systemic antiinflammatory treatment was initiated with good outcomes.