Alternative Biologic Therapy in Children Failing Conventional TNFα Inhibitors for Refractory, Noninfectious, Chronic Anterior Uveitis.

PURPOSE: A significant number of children with noninfectious, chronic anterior uveitis (CAU) fail to respond to conventional therapy; however, successful alternative biologic treatments (ABT) have not been well described. This study aims to review the clinical and treatment characteristics of children with CAU who require ABT. DESIGN: Retrospective, nonrandomized clinical study. METHODS: Setting: Tertiary center. STUDY POPULATION: Children with noninfectious CAU. OBSERVATION PROCEDURES: Clinical characteristics, uveitis course, complications, and treatment were compared among patients treated with methotrexate (MTX) monotherapy, conventional TNFα inhibitors (cTNFi), and ABT for >3 months. MAIN OUTCOME MEASURE: Success of ABT (abatacept, tocilizumab, and/or golimumab) in children failing conventional treatment. RESULTS: Of the 52 children with CAU, 75% had juvenile idiopathic arthritis. CAU was controlled in 15 children receiving MTX monotherapy, 28 receiving cTNFi, and 9 receiving ABT (n = 1, abatacept; n = 3, tocilizumab; n = 5, golimumab). Patients in the ABT group had a greater number of total ocular complications per person before ABT than those in the control groups (3.4 vs 0.7 [MTX], P < .001, and 1.5 [cTNFi], P < .001, respectively). In all 9 children on ABT, treatment led to control of CAU and topical glucocorticoids tapered to ≤2 drops/d with no new ocular complications. CONCLUSIONS: In this study, alternative biologics (abatacept, golimumab, and tocilizumab) were useful for treating CAU in children who fail MTX and cTNFi therapy. Patients who were controlled on ABT had more disease activity, ocular complications, and anti-cTNFi neutralizing antibodies (before ABT) than those managed with conventional therapy. Larger studies are required to confirm these findings.

Effectiveness of long-term infliximab use and impact of treatment adherence on disease control in refractory, non-infectious pediatric uveitis.

BACKGROUND: Refractory non-infectious uveitis is a serious condition that leads to ocular complications and vision loss and requires effective systemic treatment to control disease. The effectiveness of long-term infliximab [IFX] in refractory non-infectious childhood uveitis and the impact of treatment adherence on disease control were evaluated. METHODS: Retrospective, single-center study between December 2002 and April 2016 of 27 children with refractory non-infectious uveitis [17 with juvenile idiopathic arthritis, JIA] treated with long-term IFX [9+ months]. Disease activity was assessed prior to and while on IFX using the Standardization of Uveitis Nomenclature [SUN]. Number of visits per year with active uveitis was analyzed by repeated measures logistic regression analysis from 2 years prior to IFX initiation or from onset of uveitis until most recent visit on IFX. Incomplete treatment adherence was assessed for each visit and defined as any deviance in corticosteroid use, prescribed infusion frequency, and/or follow-up examination frequency. RESULTS: Primary outcomes were sustained uveitic and systemic disease control prior to and during IFX treatment and the impact of incomplete adherence on uveitic disease control while on IFX. Secondary outcomes included corticosteroid and glaucoma medication requirement, ocular complications and need for surgical intervention. Mean age at IFX initiation was 10.4 ± 4.5 years; initial mean dose was 6.6 ± 2.2 mg/kg [and given at weeks 0, 2, 4 and q4 weeks thereafter for 93%]. Median duration on IFX was 35 [range 9-128] months. Prior to IFX, 14/27 patients had failed adalimumab ± methotrexate [MTX]; 21/27 failed MTX. IFX led to uveitis control in 89% and arthritis control in 76% (13/17). The odds ratio of having controlled disease after IFX was 4.1 (2.6, 6.4) compared to pre-treatment visits. Topical corticosteroids and glaucoma medications were statistically decreased (p = 0.007 right eye [OD], 0.003 left eye [OS] and p = 0.001 OD, p = 0.028 OS respectively). Incomplete adherence to treatment showed 10.3 times greater odds (7.1, 15.0) of having disease activity than full adherence. CONCLUSIONS: This study adds significantly to the IFX literature by documenting outstanding uveitis control with long-term IFX treatment in non-infectious pediatric uveitis patients. Higher dosage and shorter interval were utilized without adverse effects. Importantly, this is the first study, to our knowledge, to document the significant impact of treatment adherence on uveitis control.

Rituximab for refractory granulomatous eye disease.

OBJECTIVE: To determine the effectiveness of rituximab therapy for patients with granulomatous disease of the eye. METHODS: Retrospective review was undertaken of cases seen at a single institution for ocular antineutrophil cytoplasmic antibody-associated vasculitis or sarcoidosis with persistent ocular disease despite systemic therapy. All patients were treated with rituximab and followed for at least 6 months. RESULTS: Nine patients were identified (five with antineutrophil cytoplasmic antibody-associated vasculitis, four with sarcoidosis), and all were treated for at least 6 months. Eight experienced improvement of eye disease and were able to reduce prednisone and other drug therapies. One patient remained stable, but still required high dosages of prednisone. All five patients with lung disease improved with rituximab therapy. Rituximab treatment was well tolerated. Two patients discontinued the drug due to leukopenia; however, both patients reinstituted rituximab at modified doses. CONCLUSION: Rituximab therapy was effective in controlling granulomatous ocular disease in most cases. The drug was corticosteroid-sparing and effective in refractory cases, with no severe adverse events encountered.

Ocular sarcoidosis.

Ocular disease occurs in approximately a third of sarcoidosis patients. The rate of disease varies around the world, with Japanese sarcoidosis patients having ocular disease in more than 70% of cases. If untreated, ocular disease can lead to permanent visual impairment, including blindness. The most common manifestation is uveitis, with anterior involvement often being self-limiting, whereas posterior involvement can be chronic. The diagnosis of ocular sarcoidosis in patients with known sarcoidosis usually requires a specific examination by an ophthalmologist. For patients presenting with uveitis of unknown etiology, criteria have been proposed for diagnosing ocular sarcoidosis. The treatment of ocular disease ranges from topical therapy to systemic treatments such as methotrexate. Recent reports have demonstrated that monoclonal antibodies blocking tumor necrosis factor can be quite effective for chronic refractory ocular sarcoidosis.

Expression of fibronectin isoforms bearing the alternatively spliced EIIIA, EIIIB, and V segments in corneal alkali burn and keratectomy wound models in the rat.

PURPOSE: To better understand the healing process in the wounded cornea, fibronectin (FN) isoforms bearing the alternatively spliced EIIIA, EIIIB, and V segments (EIIIA+, EIIIB+, and V+ FNs) were evaluated in alkali burn and keratectomy wound models in the rat. METHODS: Alkali burn or keratectomy wounds (both 2 mm) were created, and corneas were harvested at various time points and analyzed by indirect immunofluorescence using antibodies specific for the EIIIA, EIIIB, and V segments as well as for the total pool of FN (total FN). RESULTS: There was minimal staining for any variety of FN in the epithelium or basement membrane zone (BMZ) in normal cornea, but each antibody produced granular staining in the stroma. Bright staining for V+ and total FNs was evident at the denuded stromal surface 1 day following keratectomy. In contrast, staining for EIIIA+ and EIIIB+ FNs was negligible at 24 hours but appeared on the wound surface under the migrating unstained epithelium by the second day. BMZ staining for FN then gradually subsided, such that there was little or no staining by 6 weeks. In contrast, alkali burn wounds exhibited very little BMZ staining throughout the time course. Although there was preferential staining of the anterior aspect of Descemet membrane by anti-EIIIA and anti-EIIIB antibodies under normal conditions, the staining intensity of the anterior and posterior aspects became similar following corneal wounding. CONCLUSION: Deposition of EIIIA+ and EIIIB+ FNs in the BMZ of the keratectomy wound occurs more slowly than deposition of V+ and total FNs. EIIIA+ FN is expressed in a distribution that overlaps with that previously described for the alpha 9 integrin subunit following corneal debridement, suggesting that EIIIA-alpha 9 interactions could occur during corneal wound healing. In contrast, the relative lack of FN deposition in alkali burn wounds suggests that proteolytic degradation of FN may occur; and this, along with impairment of new FN synthesis because of cellular damage, could play a role in the high prevalence of recurrent epithelial erosions in alkali-wounded corneas.

Cataract surgery without preoperative eyedrops.

We present a technique that uses intracameral lidocaine to induce pupil dilation without using preoperative mydriatic eyedrops. After 1 or 2 drops of topical lidocaine hydrochloride 1% (Xylocaine-MPF 1%) are applied to the ocular surface, a 1.0 mm side-port incision is created through which Xylocaine-MPF 1% is injected into the anterior chamber. The lidocaine paralyzes the pupil sphincter, and adequate mydriasis occurs within 90 seconds. Epinephrine (0.3 cc of 1:1000) is added to the irrigation fluid comprising balanced salt solution (BSS), and standard phacoemulsification with intraocular lens implantation is performed. Pupil dilation is maintained or increased during the procedure. Postoperatively, the pupil returns more quickly to normal size and reaction. Using lidocaine for mydriasis instead of standard dilating drops eliminates the cardiac risk of topical sympathetic agents, decreases the time patients wait in the holding area before surgery, reduces the risk of superficial punctate keratopathy, and provides faster recovery of normal pupil function.

Pediatric airbag-associated ocular trauma and endothelial cell loss.

BACKGROUND: Airbag-associated ocular trauma among the adult population has been widely reported, but reports of these injuries in children are sparse. Laboratory experiments suggest that airbag-associated ocular trauma may cause endothelial cell loss, but reports of in vivo human endothelial cell counts are anecdotal. METHODS: A retrospective chart review was performed of all patients with airbag-associated ocular trauma at a pediatric hospital from 1995 to 2001. From 2001 to 2002, endothelial cell counts were obtained from 9 eyes of airbag-associated ocular trauma subjects and 22 eyes of control subjects. RESULTS: Sixteen patients were identified; all had periocular abrasions, edema, and/or ecchymosis. Other ocular injuries included corneal abrasions (n = 9 or 56%), corneal edema (n = 8 or 50%), hyphema (n = 7 or 44%), lens opacities (n = 5 or 31%), and macular scars (n = 2 or 12%). Three eyes of three patients required intraocular surgery. Unilateral visual loss (hand-motions, 20/100) occurred in two patients. A decrease in mean endothelial cell count of 547 cell/mm2 (P =.01) was found in the airbag-associated ocular trauma group eyes when compared with control group eyes. CONCLUSIONS: The present study includes the largest reported case series of pediatric airbag-associated ocular trauma. Airbag-associated ocular trauma may necessitate intraocular surgery, may result in permanent visual loss, and may cause endothelial cell loss in pediatric patients.

Intracameral tissue plasminogen activator use in a large series of eyes with valved glaucoma drainage implants.

OBJECTIVE: To describe the efficacy and complications of intracameral tissue plasminogen activator (tPA) in a large series of glaucomatous eyes with valved glaucoma drainage implants (GDIs). METHODS: A retrospective analysis of 620 Ahmed and Krupin aqueous shunts implanted between December 1992 and May 2001 identified 36 eyes treated with intracameral tPA for total or imminent tube obstruction by fibrin and/or blood. For a successful ocular outcome, tPA use must prevent the need for additional glaucoma surgery to replace or revise an occluded drainage implant. RESULTS: Intracameral tPA successfully cleared or prevented tube occlusion by fibrin/blood clots in 32 (88.9%) of 36 eyes. Multiple tPA injections were administered in 38.9% of eyes, and the mean number of injections required to achieve successful outcomes was 1.6. The mean +/- SD tPA dose per injection was 9.8 +/- 3.1 micro g, and the mean +/- SD total tPA dose required to achieve successful outcomes was 15.5 +/- 9.9 micro g. For injections to be successful in totally occluded tubes (n = 31), the mean +/- SD intraocular pressure change 24 hours after tPA administration was -21.2 +/- 15.6 mm Hg. Significant complications, including severe hyphema, profound hypotony, and anterior chamber flattening, occurred after 10.9% of tPA administrations. CONCLUSION: Intracameral tPA clears and prevents obstruction of valved GDIs by fibrin and/or blood clots.

Ocular manifestations of sarcoidosis.

Ophthalmic involvement in sarcoidosis may cause significant sight-threatening illness for patients. Studies of patients with histologically proven sarcoidosis have found 25 to 50% of patients to have ocular manifestations. The frequency in which eye disease is seen and the course that it takes vary with age, race, and geography. This article discusses relevant aspects of the ocular manifestations of sarcoidosis for the internist and pulmonologist. Overall disease presentation, specific types of ocular involvement, evaluation strategies, and treatment considerations are discussed.