Diagnostic Utility of QuantiFERON-Gold Testing in Patients with Ocular Inflammation in a Low-Endemic Tuberculosis Region.

PURPOSE: To evaluate the diagnostic value of QuantiFERON Gold (QFT-G) testing for ocular inflammation in a low prevalence tuberculosis (TB) area. DESIGN: Diagnostic utility analysis. METHODS: A review was performed for all uveitis patients who underwent QFT-G testing at the University of Colorado Eye Center from 2009 to 2022. Records were reviewed to assess QFT-G positivity rate and to identify which patients were tested for diagnostic purposes, defined as meeting the Standardization of Uveitis Nomenclature (SUN) criteria for tubercular uveitis (TBU): anterior uveitis with iris nodules, serpiginous-like choroiditis, choroidal nodule resembling a tuberculoma, multifocal choroiditis, or occlusive retinal vasculitis. RESULTS: A total of 388 patients with uveitis underwent QFT-G testing, of which 17 (4.38%) were positive. Only one (5.88%) patient had true TBU with anterior uveitis with iris nodules. The remaining 16 (94.1%) patients did not meet SUN criteria for TBU and were incidentally found to be QFT-G positive during laboratory work-up prior to immunosuppression. The positive predictive value was 100% when QFT-G testing was performed in patients who met SUN criteria for TBU, whereas the positive predictive value was 0% for QFT-G testing performed in patients who did not meet SUN criteria for TBU. CONCLUSION: In low prevalence areas, the majority of QFT-G positive tests in uveitis patients are coincidental and unrelated to their uveitic disease process. The diagnostic value of a TB test is likely to be minimal unless the SUN clinical criteria for tubercular uveitis are met.

Risk factors for failing sub-Tenon's triamcinolone acetonide for uveitic macular edema.

BACKGROUND: Sub-Tenon's triamcinolone acetonide (STA) is less effective than intravitreal corticosteroids in the treatment of uveitic macular edema (ME), but does have some relative advantages, including substantially lower cost and decreased risk of post-injection ocular hypertension. It would be useful for clinicians to know which eyes may respond well to STA and not necessarily require intravitreal therapy. The objective of this study is to identify risk factors for failing STA for the treatment of uveitic ME. MAIN BODY: A retrospective cohort study was performed. Medical records were reviewed of patients who underwent STA for the treatment of uveitic ME between January 1, 2013, and July 31, 2022, at the University of Colorado Hospital. Uveitic ME was defined by a central subfield thickness (CST) greater than 320 µm or the presence of intra-retinal cystoid spaces on optical coherence tomography (OCT), or by the presence of petaloid macular leakage on fluorescein angiography (FA). Data collected included age, race/ethnicity, sex, history of diabetes mellitus, anatomic classification of uveitis, use of corticosteroids, use of immunomodulatory therapy, presence of intra-retinal fluid on OCT, CST on OCT, and presence of petaloid macular leakage on FA. STA failure was defined as the need for additional therapy within 12 weeks of STA due to persistent or worsening uveitic ME. One hundred eighty eyes from 131 patients were included. Forty-two eyes (23.3%) were considered treatment failures. In univariate and multivariable analysis, higher baseline CST was associated with a higher likelihood of failing STA (OR 1.17 for each 30 µm increase in CST, P = 0.016). CONCLUSIONS: STA, while not as potent as intravitreal corticosteroids for the treatment of uveitic ME, was still an effective therapy, particularly for patients with lower baseline CST. Given its lower side effect profile and cost compared to intravitreal treatments, clinicians could consider STA as an initial treatment for mild uveitic ME.

Uveitis in the Setting of Co-Existing Systemic Sarcoidosis and Multiple Sclerosis.

We report a case of intermediate uveitis in the setting of both systemic sarcoidosis and multiple sclerosis. A 68-year-old female was diagnosed with bilateral granulomatous intermediate uveitis and cystoid macular edema. Initial systemic work-up was unrevealing. The uveitis was treated successfully with local corticosteroid injections. Eighteen months after presentation, the patient developed new systemic symptoms. Additional testing revealed systemic lymphadenopathy, with biopsy showing non-caseating granulomas, leading to a diagnosis of sarcoidosis. However, MRI of the brain and spinal cord along with cerebrospinal fluid analysis was consistent with MS. The management of the uveitis and systemic inflammation was co-managed by ophthalmology, neurology, and rheumatology, and eventually controlled with leflunomide and rituximab. Patients can rarely have co-existing systemic sarcoidosis and multiple sclerosis. Although challenging to diagnose, radiographic findings and cerebrospinal fluid analysis can be helpful to differentiate multiple sclerosis and neurosarcoidosis. Management of these patients requires coordination between multiple specialties.

Cataract Surgery Outcomes in Patients with Non-ocular Autoimmune Disease.

INTRODUCTION: While phacoemulsification cataract extraction is generally highly effective and safe, patients with a history of uveitis are at higher risk for postoperative complications and often require a modified perioperative medication regimen. No data exists on risks of postoperative complications and persistent anterior uveitis (PAU) in patients with non-ocular autoimmune disease. METHODS: Medical records were reviewed of patients who underwent phacoemulsification cataract surgery with intraocular lens implantation between January 1, 2014 and December 31, 2019 at the University of Colorado Hospital (UCH) as part of a retrospective cohort study. Exclusion criteria included patient history of ocular inflammation and cataract surgery combined with another intraocular surgery. Patients were only included as having autoimmune disease if the diagnosis was confirmed by a relevant specialist at UCH. Patients with autoimmune disease were then stratified into systemic versus organ-specific autoimmune disease, and patients with systemic autoimmune disease were further stratified into immunosuppressed and not immunosuppressed at the time of cataract surgery. Patients with PAU were identified according to the Standardization of Uveitis Nomenclature Working Group. Data including sex, race/ethnicity, intraoperative cumulative dissipated energy (CDE), and postoperative best-corrected visual acuity (BCVA) and intraocular pressure (IOP) were obtained. RESULTS: A total of 422 eyes from 248 patients had confirmed autoimmune disease, compared to a control group of 10,201 eyes. The autoimmune and systemic autoimmune disease groups were not more likely to have postoperative complications or PAU compared to the control group. Immunosuppression status among the systemic autoimmune disease group was also not associated with postoperative complications or PAU. CONCLUSION: Patients with non-ocular autoimmune disease do not appear to be at higher risk for postoperative complications, including worse BCVA or increased rates of IOP elevation and PAU, following phacoemulsification cataract surgery. These patients do not appear to require modification of the typical perioperative medication regimen.

Risk of failing both methotrexate and mycophenolate mofetil from the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial.

BACKGROUND: The antimetabolites methotrexate (MTX) and mycophenolate mofetil (MMF) are commonly used as initial corticosteroid-sparing treatment for uveitis. There is little data examining risk factors for failing both MTX and MMF. The objective of this study is to determine risk factors for failing both MTX and MMF in patients with non-infectious uveitis. MAIN BODY: This is a sub-analysis of the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial, which was an international, multicenter, block-randomized, observer-masked, comparative effectiveness trial comparing MTX and MMF as initial treatments for non-infectious uveitis. This study was undertaken at multiple referral centers in India, the United States, Australia, Saudi Arabia and Mexico between 2013 and 2017. A total of 137 patients who completed all 12 months of follow-up from the FAST trial, were included in this study. The primary outcome was failing both antimetabolites over the 12 months of the trial. Potential predictors included: age, sex, bilateral involvement, anatomic location of the uveitis, presence of cystoid macular edema (CME) and retinal vasculitis at baseline visit, uveitis duration, and country/study sites as risk factors for failing both MTX and MMF. The presence of retinal vasculitis posterior to the equator on fluorescein angiogram was associated with failing both MTX and MMF. CONCLUSION: Retinal vasculitis may be a risk factor for failing multiple antimetabolites. Clinicians could consider more quickly advancing these patients to other medication classes, such as biologics.

Reduced Dose Methotrexate and Mycophenolate Mofetil in Noninfectious Uveitis: A Sub-Analysis from the First-Line Antimetabolites as Steroid Sparing Therapy (FAST) Trial.

PURPOSE: Some patients taking methotrexate (MTX) or mycophenolate mofetil (MMF) experience intolerable side effects at full doses. We evaluated whether dose reduction affected treatment outcomes in uveitis patients. METHODS: Subanalysis of the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial. Patients were randomized to receive MTX (25 mg weekly) or MMF (3 g daily). A pre-specified dose reduction protocol could be employed for intolerable side effects. Primary analysis was performed at 6 months. RESULTS: 43/194 patients (22%) required dose reduction. 88/151 patients (58%) on maximum doses and 32/43 patients (74%) on reduced doses were deemed treatment successes at 6 months. The odds ratio point estimate (1.60, 95% CI 0.72-3.74) favored dose-reduction but this was not significant. Following reduction, adverse events improved at the subsequent study visit (79 events reduced to 63 events). CONCLUSION: Dose reduction of antimetabolites was not associated with worse outcomes in this subanalysis of a uveitis trial.

Single Institution Experience of Intravitreal 0.18-mg Fluocinolone Acetonide Implant for Noninfectious Uveitis.

PURPOSE: To report the outcomes of the 0.18-mg fluocinolone acetonide implant (FAi) in the treatment of noninfectious uveitis. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients who received the 0.18-mg FAi for the treatment of noninfectious uveitis affecting the posterior segment (NIU-PS) between July 1, 2019, and August 31, 2021, at the University of Colorado. Patients were excluded if they did not have ≥ 6 months of follow-up after the placement of the implant. METHODS: Data including age, race/ethnicity, sex, uveitis diagnosis, history and current use of anti-inflammatory therapy, use of short-acting corticosteroid injections within the 3 months before the 0.18-mg FAi implantation, visual acuity, intraocular pressure (IOP), grading of anterior chamber and vitreous cell, and presence of cystoid macular edema were obtained from the medical charts. Uveitis recurrence was defined as any increased inflammation that required additional anti-inflammatory therapy. MAIN OUTCOME MEASURES: Probability of remaining recurrence-free after the placement of the 0.18-mg FAi. RESULTS: Sixty-four eyes from 42 patients were included. The overall probability of remaining recurrence-free was 68.8% at 6 months and 52.6% at the 12-month follow-up. Eyes that remained recurrence-free at 12 months had a younger mean age than eyes that had a recurrence within 12 months (P = 0.02). Eyes that received a short-acting corticosteroid injection before the 0.18-mg FAi were more likely to have a recurrence by 6 months of follow-up than eyes that did not receive a pre-FAi corticosteroid injection (P = 0.05). Initiation or addition of IOP-lowering eyedrops was required in 15.6% of eyes, and 4.7% of eyes required IOP-lowering surgery after 0.18-mg FAi placement. CONCLUSIONS: The 0.18-mg FAi appears to be an effective option in the management of NIU-PS, with relatively low rates of ocular hypertension requiring intervention. The use of short-acting corticosteroid injections before the placement of the 0.18-mg FAi does not seem to improve the effectiveness of the 0.18-mg FAi, although this may be partially because of selection bias. Additional studies are required to determine patients who are the optimal candidates for this therapy.

Bilateral choroidal effusions and angle closure in the setting of systemic capillary leak syndrome from HLA-directed vaccine and pembrolizumab therapy for squamous cell carcinoma.

Purpose: Immunotherapy has become an important addition to oncology treatment plans in recent years. As these therapies become more widely employed, many unique side effects have been reported. In ophthalmology the most well-documented side effects of immune checkpoint inhibitors (ICI) include uveitis, macular edema and dry eye syndrome. This manuscript describes a rare case of bilateral choroidal effusions and secondary angle narrowing in the setting of systemic capillary leak syndrome (SCLS) from an HLA-directed vaccine and an ICI, pembrolizumab, for the treatment of stage IV squamous cell carcinoma (SCC) of the lung. Observations: A 67-year-old male with a history of stage IV SCC of the lung status-post pneumonectomy presented to the emergency department due to functional decline, anasarca, and dyspnea after receiving an HLA-directed vaccine in combination with pembrolizumab. Extensive workup revealed that his symptoms were secondary to SCLS. Ophthalmology was consulted due bilateral choroidal detachments seen on magnetic resonance imaging. B-scan ultrasound and ultrasound biomicroscopy revealed large, non-appositional choroidal effusions with anterior rotation of the ciliary body. Given minimal response to oral steroid therapy, sub-Tenon's triamcinolone acetonide, atropine, and intraocular pressure-lowering eyedrops were initiated with a good response. Conclusions and Importance: Choroidal effusions and secondary angle closure can be rare complications of SCLS in the setting of ICIs. Clinicians must be aware of the potentials side effects of ICI therapy, as these medications become more commonly used.

Ocular manifestations of rheumatoid arthritis.

PURPOSE OF REVIEW: This article summarizes the pathophysiology of rheumatoid arthritis and common ocular manifestations that it is associated with: keratoconjunctivitis sicca, episcleritis, scleritis, and peripheral ulcerative keratitis. RECENT FINDINGS: Newer biologic agents are being used to effectively treat rheumatoid arthritis and its ocular manifestations. SUMMARY: The eye is a frequent extra-articular site of inflammation in patients with rheumatoid arthritis. Ocular involvement can range from more benign conditions such as keratoconjunctivitis sicca and episcleritis, to potentially vision and globe-threatening diseases like scleritis and peripheral ulcerative keratitis. Clinicians should be aware of these ophthalmic manifestations and the various treatment options that are available. Coordination between ophthalmology and rheumatology is helpful in the treatment of these patients.

Bilateral anterior and intermediate uveitis in SARS-CoV-2 associated multisystem inflammatory syndrome in a pediatric patient.

PURPOSE: To report a case of bilateral anterior intermediate uveitis after recovery from SARS-CoV-2 associated multisystem inflammatory syndrome in children (MIS-C). CASE REPORT: A 9-year-old male presented with bilateral anterior intermediate uveitis with fluorescein angiography (FA) leakage of the disc and peripheral vasculature 1 month after recovery from MIS-C. He was treated with difluprednate 0.05% in both eyes with resolution of FA leakage, but our patient has required an extended treatment of topical therapy and the need long term immunosuppression. CONCLUSIONS: This is a case of uveitis presenting after recent MIS-C related to SARS-CoV-2. Ongoing follow up and monitoring is required, and it is important for the ophthalmologist and rheumatologist to be aware of this rare complication during the current COVID-19 pandemic.

Occult cause of uveitis-glaucoma-hyphema syndrome diagnosed during treatment with endocyclophotocoagulation (ECP).

Purpose: To describe uveitis-glaucoma-hyphema (UGH) syndrome secondary to a posterior chamber intraocular lens (PCIOL) within the capsular bag in which pathogenic changes to the ciliary body were observed and treated with endocyclophotocoagulation (ECP). Observations: An 85-year-old woman who had cataract surgery in her right eye four years ago presented with recurrent, unilateral, open-angle, hypertensive uveitis in her right eye. Her presentations were characterized by decreased vision, elevated intraocular pressure, corneal edema, a mixed anterior chamber reaction, and pigmented anterior vitreous cells. She had a frank vitreous hemorrhage during two episodes. Ultrasound biomicroscopy revealed a dense Soemmerring ring in her right eye without evidence of PCIOL-iris or PCIOL-ciliary body chafe. Subsequent ECP revealed whitened and atrophic ciliary processes adjacent to a tilted haptic within the capsular bag, consistent with chronic PCIOL-ciliary body chafe. ECP was applied to the affected ciliary processes, which successfully eliminated recurrences. Conclusions and importance: UGH can rarely occur due to an PCIOL within the capsular bag. In cases where ultrasound biomicroscopy (UBM) does not show abnormalities and clinical suspicion remains high, ECP can be a useful adjunct to observe and treat abnormalities of the ciliary body.

Dupilumab-associated cicatrizing ocular disease.

Purpose: To describe three cases of bilateral cicatrizing conjunctivitis associated with dupilumab treatment for atopic dermatitis. Observations: Case 1 is a 69 year-old male with a history of mild, stable cicatrizing conjunctivitis thought to be secondary to atopic dermatitis. His cicatrizing disease progressed significantly after starting dupilumab, and then stabilized after dupilumab was discontinued. Case 2 is a 72 year-old male who presented with bilateral cicatrizing conjunctivitis. His symptoms of ocular erythema and irritation started shortly after initiating dupilumab for atopic dermatitis. The dupilumab was discontinued and the patient's symptoms resolved and ocular surface scarring stabilized. Case 3 is a 47 year-old male with a history of allergic conjunctivitis who was found to have new onset unilateral symblepharon approximately 12 months after starting dupilumab for atopic dermatitis. The dupilumab was discontinued and his ocular disease stabilized. However, his cutaneous symptoms worsened significantly, so dupilumab was restarted at half the previous dose. His atopic dermatitis symptoms improved and cicatrizing conjunctivitis remained stable on this regimen. Conclusions and importance: Cicatrizing conjunctivitis with symblepharon formation distinct from ocular cicactricial pemphigoid is a potential side effect of dupilumab therapy for atopic dermatitis. Progression of the cicatrization appears to halt with discontinuation, or potentially dose reduction, of dupilumab.

Evaluation of the SUN Classification Criteria for Uveitides in an Academic Uveitis Practice.

PURPOSE: To evaluate the new Standardization of Uveitis Nomenclature (SUN) classification criteria for uveitides by applying them to patients in an academic uveitis practice. DESIGN: Evaluation of classification criteria. METHODS: The charts of all patients attending the uveitis service at the University of Colorado Hospital between January 1, 2013, and December 31, 2020, were reviewed. Patients with scleritis, ocular cicatricial pemphigoid, and peripheral ulcerative keratitis were excluded. We attempted to classify each patient's uveitis using the SUN classification criteria. Classification attempts were made within the relevant anatomical or infectious categories for their pathology but did not necessarily have to match their clinical diagnosis by a uveitis specialist. We recorded whether classification was possible as well as their clinical diagnosis by a uveitis specialist. RESULTS: All patients attending the uveitis clinic at our academic institution between January 1, 2013, and December 31, 2020, were reviewed. Of the 1143 patients with uveitis, 572 (50.0%) had a disease that was not listed in the SUN classification system, and so no attempt to classify these patients was possible. Of the remaining 571 patients, 522 (91.4%) were able to be classified by SUN and in 492 (94.3%) of the 522 cases, their SUN classification matched their clinical diagnosis by a uveitis specialist. CONCLUSIONS: Half of the patients at an academic uveitis practice had a disease for which no SUN classification criteria existed. In cases where classification by SUN could be attempted, the system performed well and generally agreed with their clinical diagnosis.

Endoscopic Cyclophotocoagulation Combined with Phacoemulsification Increases Risk of Persistent Anterior Uveitis Compared to Phacoemulsification Surgery Alone.

PURPOSE: To evaluate if the addition of endoscopic cyclophotocoagulation (ECP) to uncomplicated phacoemulsification cataract extraction increases the risk of persistent anterior uveitis (PAU) compared to phacoemulsification alone. PATIENTS AND METHODS: Retrospective analysis of patients who had either phacoemulsification alone or combined with endoscopic cyclophotocoagulation from January 1, 2014 to December 31, 2017. Visual acuity, intraocular pressure, presence of anterior chamber cells, and steroid usage were analyzed pre- and post-operatively. Patient eyes with a history of uveitis, autoimmune disease, complicated cataract surgery, combined surgery other than ECP, and less than 3 months of follow-up were excluded. RESULTS: This study consisted of 4423 eyes from 2903 patients, meeting the inclusion criteria (phacoemulsification only group n=4242 and phacoemulsification/ECP group n=181 eyes). PAU developed in 14.9% in the phacoemulsification with ECP group compared to 1.7% who had phacoemulsification alone. White patients had a 17.9 (95% CI: 7.8-41.1, p<0.0001) increased odds of developing persistent anterior uveitis with a combined procedure compared to phacoemulsification only, while Non-white patients had a 5.8 (95% CI: 2.8-12.1, p<0.0001) increased odds. Despite the higher odds ratio in White patients, this group had a significantly lower rate of PAU compared to Non-white patients after phacoemulsification/ECP. CONCLUSION: The addition of endoscopic cyclophotocoagulation to phacoemulsification significantly increases the risk of developing PAU in the post-operative period compared to phacoemulsification alone.

Tattoo Granulomas With Uveitis.

Bilateral intraocular inflammation and simultaneous development of tattoo granulomas has been described in several case reports. The pathophysiology of this process is poorly understood, and it has been hypothesized that it could be a similar mechanism to systemic sarcoidosis versus a delayed hypersensitivity response. Granulomatous tattoo reaction with associated uveitis can manifest with or without evidence of systemic sarcoidosis, and it is usually responsive to immunosuppression and/or tattoo removal. We present a patient with no prior diagnosis of sarcoidosis who developed bilateral panuveitis and tattoo changes suggestive of tattoo granulomas with uveitis (TAGU). The patient was initially managed with intraocular steroids and systemic steroids with minimal improvement of symptoms. The patient later required steroid sparing therapy with a tumor factor inhibitor to achieve remission. There is a growing prevalence of tattooing among the general population and a low reported rate of tattooing complications. Granulomatous tattoo reaction with associated uveitis should be a consideration in patients with tattoos presenting with "idiopathic" uveitis.

Retinal artery occlusion followed by contralateral amaurosis fugax in association with eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome).

PURPOSE: To describe two cases of retinal artery occlusion followed by contralateral amaurosis fugax associated with eosinophilic granulomatosis with polyangiitis (EGPA, formerly known as Churg-Strauss syndrome). OBSERVATIONS: Case 1 is a 57 year-old male who presented with transient vision loss in the right eye two weeks after a cilioretinal artery occlusion in the left eye. Evaluation eventually led to a diagnosis of EGPA. The patient was treated with high-dose steroids followed by systemic immunomodulatory therapy. Vision in the right eye recovered to 20/20 with no further episodes of vision loss. Case 2 is a 55 year-old male with a known diagnosis of EGPA who presented with transient vision loss in the right eye four weeks after a central retinal artery occlusion of the left eye. This patient also successfully recovered vision in the right eye after treatment with high-dose steroids following a change in his systemic immunomodulatory therapy. CONCLUSIONS AND IMPORTANCE: While ANCA-vasculitides are an uncommon cause of retinal artery occlusion and amaurosis fugax, it is important that they remain in the differential diagnosis, as good visual outcomes can be achieved with prompt initiation of appropriate therapies.

Risk Factors Associated with Persistent Anterior Uveitis after Cataract Surgery.

PURPOSE: To identify risk factors for the development of persistent anterior uveitis (PAU) following uncomplicated phacoemulsification cataract extraction in patients without histories of uveitis or autoimmune diseases. DESIGN: Retrospective cohort study. METHODS: Medical records were reviewed of patients who underwent phacoemulsification cataract extraction with intraocular lens implantation between January 1, 2014, and December 31, 2016, at the University of Colorado Hospital. Exclusion criteria included patient history of autoimmune disease and/or uveitis, cataract surgery combined with another intraocular surgery, and complicated cataract surgery. Patients with PAU were identified according to Standardization of Uveitis Nomenclature Working Group criteria. Data including sex, race/ethnicity, surgery length and cumulative dissipated energy (CDE), and postoperative visual acuity (VA) and intraocular pressure (IOP) were obtained. Main outcome measurements were risk factors for the development of PAU. RESULTS: The charts of 3,013 eyes from 2,019 patients were reviewed. A total of 61 eyes (2.0%) from 48 patients developed PAU. African Americans were more likely than whites to develop PAU (relative risk = 11.3; P < 0.0001). Age, sex, surgery length, and CDE were not risk factors. Patients with PAU did not have worse VA than those without PAU, and African Americans with PAU did not have worse VA or IOP than the other races with PAU. Eighteen of the 61 eyes (29.5%) also developed cystoid macular edema. CONCLUSIONS: African Americans have a higher risk of developing PAU after uncomplicated phacoemulsification cataract extraction. The mechanism leading to this is unclear. Although PAU requires prolonged treatment, it does not appear to lead to worse visual outcomes.