Update on the systemic management of noninfectious uveitis in children and adolescents.

Noninfectious uveitis (NIU) in children and adolescents is a rare but treatable cause of visual impairment in children. Treatments for pediatric NIU and their side effects, along with the risks of vision loss and the need for long-term disease monitoring, pose significant challenges for young patients and their families. Treatment includes local and systemic approaches and this review will focus on systemic therapies that encompass corticosteroids, conventional synthetic disease-modifying antirheumatic drugs (csDMARD), and biological disease-modifying antirheumatic drugs (bDMARD). Treatment is generally planned in a stepwise approach. Methotrexate is well-established as the preferential csDMARD in pediatric NIU. Adalimumab, an antitumor necrosis factor (TNF) agent, is the only bDMARD formally approved for pediatric NIU and has a good safety and efficacy profile. Biosimilars are gaining increasing visibility in the treatment of pediatric NIU. Other bDMARD with some evidence in literature for the treatment of pediatric NIU include infliximab, tocilizumab, abatacept, rituximab and, more recently, Janus kinase inhibitors. Important aspects of managing children on these systemic therapies include vaccination issues, risk of infection, and psychological distress. Also, strategies need to address regarding primary nonresponse/secondary loss of response to anti-TNF treatment, biological switching, and monitoring regimens for these drugs. Optimal management of pediatric uveitis involves a multidisciplinary team, including specialist pediatric uveitis and rheumatology nurses, pediatric rheumatologists, psychological support, orthoptic and optometry support, and play specialists.

Intravitreal Fluocinolone 0.19mg Implant in the Management of Chronic Non-Infectious Uveitis: 12-Month Outcomes from a Single Tertiary Centre.

AIM: To present efficacy and safety of 0.19 mg fluocinolone acetonide insert (FAi) to treat chronic noninfectious uveitis (NIU) in a single referral center. METHODS: A retrospective observational clinical study of 11 eyes with NIU complicated by chronic cystoid macular edema (CMO). RESULTS: The main indication for treatment was chronic CMO in all 11 eyes. The mean central retinal thickness (CRT) at baseline was 435 µm ± 176, improving to 296 µm ± 67 at 12 months. Raised intraocular pressure (IOP) was the commonest adverse event. An IOP >21 mmHg was observed in three eyes, and >30 mmHg in one eye, managed with topical therapy. The mean best corrected visual acuity (BCVA) was stable at 12 months. There were no observed recurrences of uveitis. Two eyes received adjunctive treatment for worsening CRT. CONCLUSIONS: Our results suggest FAi is an effective maintenance treatment for NIU with favorable functional and anatomical outcomes.

Paracentral Acute Middle Maculopathy in A Young Girl Treated with Interferon-Beta for Nasopharyngeal Carcinoma.

PURPOSE: To describe a case of interferon-beta retinopathy associated with paracentral acute middle maculopathy. CASE REPORT: A 15-year-old girl with Epstein-Barr virus-positive advanced nasopharyngeal carcinoma WAS REFERRED with reduced visual acuity. Multimodal imaging findings, including optical coherence tomography angiography, at presentation and evolution following cessation of interferon therapy are presented. CONCLUSION: The presentation of paracentral acute middle maculopathy in this patient supports the presumed ischaemic pathogenesis in interferon retinopathy. The imaging findings provide evidence of deep capillary plexus involvement in interferon retinopathy with evolution to permanent structural damage within the inner nuclear layer.

High dose cefuroxime causing retinal toxicity in a patient undergoing trabeculectomy.

PURPOSE: To present a case of severe retinal toxicity secondary to high dose intracameral cefuroxime administered during trabeculectomy glaucoma surgery. We describe the clinical features and management, and describe serial multimodal imaging and electrophysiological findings. Intracameral cefuroxime (ICC) and subconjunctival cefuroxime (SCC) are routinely administered during ocular surgeries to prevent postoperative endophthalmitis. Cefuroxime toxicity with both standard (1mg/0.1mL) and high doses of ICC (2-100mg) and SCC (31.25mg) have been reported. To the best of our knowledge, this is the first report of cefuroxime retinal toxicity in trabeculectomy surgery, which is of particular significance because of the possible differences in pharmacokinetics within the eye. OBSERVATIONS: A 69-year-old male with primary open-angle glaucoma, underwent right trabeculectomy, augmented with mitomycin C (0.2mg/mL). The patient inadvertently received cefuroxime 12.5mg/0.1mL as an intracameral rather than a subconjunctival injection. Within 4 hours, the error was discovered and the patient underwent immediate anterior chamber (AC) washout. His right best-corrected visual acuity was hand movements, and he rapidly developed uveitis including AC cells and moderate vitritis and haze. Optical coherence tomography (OCT) demonstrated serous macular detachment, characteristic schisis-like changes in the outer nuclear layer and ellipsoid zone disruption. Multi-focal electroretinograms (ERG) identified deficits undetected by full-field ERG. He was successfully managed with intensive local topical corticosteroid, non-steroidal therapy and peri-ocular corticosteroid injection. CONCLUSIONS AND IMPORTANCE: As ICC and SCC are routinely used in intra-ocular surgery to prevent endophthalmitis, ophthalmologists need to be aware of this potential complication and consider this in patients with unexplained reduced vision post-operatively. Theatre teams need to be vigilant about potential dilution and administration errors to ensure that the correct concentration and volume of cefuroxime is given via the correct route. We highlight the risks of high dose intracameral injection, including uveitis and retinal toxicity, and the utility of serial OCT, and full-field and multi-focal ERGs in this condition. We report a favourable outcome with significant and rapid improvement in retinal structure and function observed during follow-up. A literature review of the condition is presented.

Avascular Necrosis of Bone in Patients with Uveitis Treated with Systemic Corticosteroids.

PURPOSE: To identify the prevalence, risk factors and outcomes of avascular necrosis (AVN) in patients with chronic uveitis. METHODS: A retrospective study of patients with corticosteroid-induced AVN treated at Manchester Uveitis Clinic between 1991 and 2019. RESULTS: From a cohort of 4478 patients, 1698 had been treated with systemic corticosteroids. Five patients with AVN were identified (prevalence 0.29%). The mean age at diagnosis of AVN was 49 years. All 5 patients were using systemic immunosuppression. Four patients developed femoral head AVN in 7 joints, one had bilateral knee osteonecrosis. The mean duration of corticosteroid before AVN was 38 months; the mean dose at onset was 17mg/day and the mean cumulative dose was 18,860mg. Three patients required total hip replacements but management was conservative for others. There was no permanent disability. CONCLUSIONS: AVN is a rare but severe complication of corticosteroid therapy. Clinicians should be vigilant for symptoms of bone pain as early detection and cessation of corticosteroids can reverse incipient AVN and avoid surgery.

Ocular Involvement in the Histiocytoses: A Literature Review with an Illustrative Case Series.

PURPOSE: To describe and illustrate recent reclassification and clinical descriptions of the histiocytoses, diagnosis and management, and effects on the eye and adnexae. PATIENTS AND METHODS: Literature review with an illustrative case series of seven patients with histiocytosis and ophthalmic involvement from a single tertiary centre. RESULTS: Skin lesions with signs including eyelid mass, orbital bone destruction, bizarre keratic precipitates, limbal or iris mass, haemorrhagic anterior uveitis, subretinal lesions of uncertain etiology, ischaemic retinopathy, optic neuropathy, and apparent steroid-resistant inflammations should be comprehensively investigated. CONCLUSIONS: Ophthalmic involvement in histiocytosis is rare. Clinical manifestations vary from limited single-organ disease to lethal systemic infiltration or malignancy. Radiology may identify lesions for biopsy. Histology with appropriate markers is essential. Oncology advice may be required.

Tubulointerstitial nephritis and uveitis (TINU) syndrome: a review.

Inflammation of renal interstitium and uveal tissue establishes the two components of tubulointerstitial nephritis and uveitis (TINU) syndrome. Although believed to occur more frequently in young females, a broad spectrum of patients can be affected. Both renal and eye disease can be asymptomatic and may not manifest simultaneously, having independent progressions. Renal disease manifests as acute kidney injury and may cause permanent renal impairment. Eye inflammation can manifest in different anatomical forms, most commonly as bilateral anterior uveitis and may progress to a chronic course. TINU syndrome accounts for approximately 1%-2% of uveitis in tertiary referral centres. A literature review covering the clinical features, pathogenesis, diagnosis and treatment is presented.

Incidence, management and outcome of raised intraocular pressure in childhood-onset uveitis at a tertiary referral centre.

BACKGROUND/AIMS: To investigate the incidence, management and outcome of uveitis and raised intraocular pressure (IOP) in children treated at the Manchester Uveitis Clinic (MUC). METHODS: This was a retrospective, observational study of patients who presented with uveitis under the age of 16 to the MUC from July 2002 to June 2016. RESULTS: A total of 320 children were included in the study. Out of these, 55 (17.2%) patients (75 eyes) were found to have raised IOP requiring treatment. The mean age at diagnosis of uveitis and at first recorded raised IOP was 8.2±4.3 and 10.8±3.6 years, respectively. The pre-treatment IOP was 32.3±6.6 mm Hg and the IOP at the final visit was 15.5±3.7 mm Hg (median follow-up period, 43.7 months) on a median number of 0 medications. Twenty-eight eyes (37.3%) required glaucoma drainage surgery, and eight eyes (12.5%) had cyclodiode laser before this. Kaplan-Meier analysis showed that 11.5% of eyes required glaucoma surgery at 1 year after diagnosis of raised IOP, increasing to 50.0% by 5 years. The best-corrected visual acuity at diagnosis of uveitis was 0.26±0.42 logMAR, which remained stable at 0.28±0.65 logMAR at final follow-up visit. Four eyes (5.3%) from four patients fulfilled the definition of blindness by the WHO criteria. The mean cup:disc ratio at final follow-up was 0.4. CONCLUSION: Our cohort of children with raised IOP appeared to have a good outcome overall through aggressive medical and surgical management. Regular long-term follow-up is recommended, and early surgical intervention in eyes with uncontrolled IOP can prevent loss of vision.

Miliary tuberculosis developing during adalimumab treatment for Behçet's disease with uveitis.

Tumour necrosis factor-alpha (TNF-α) is a key proinflammatory cytokine in non-infective uveitis (NIU). Adalimumab, an anti-TNF-α monoclonal antibody, is approved for the treatment of severe NIU by the European Medicines Agency. There is a recognised risk of serious infections, including tuberculosis (TB), during anti-TNF-α therapy in systemic immune-mediated diseases. We describe miliary pulmonary TB during adalimumab therapy for severe NIU. To our knowledge, this is the first detailed report of this complication in a patient with uveitis. We present the challenges of managing vision-threatening uveitis during life-threatening infection necessitating withdrawal of adalimumab and oral immunosuppression therapy. Uveitis activity was controlled during anti-TB therapy with oral corticosteroid therapy.

An unusual case report of primary vitreoretinal lymphoma.

BACKGROUND: Primary vitreoretinal lymphoma (PVRL) is a rare ocular condition and its diagnosis remains a challenge. The clinical presentation is variable and it can masquerade as chronic intermediate or posterior uveitis. We report an unusual case of primary central nervous system lymphoma (PCNSL) presenting as migrating retinal lesions with unique shapes. The diagnostic challenges are described and the clinical features of intraocular lymphoma are reviewed. CASE PRESENTATION: A 53 year-old gentleman presented with unilateral visual disturbance and a wide area of retinal whitening with sharp borders temporal to the macula, corresponding to hyper-reflective subretinal changes on optical coherence tomography (OCT). The lesion resolved spontaneously after 6 weeks but was replaced by multiple punctate sub-retinal and sub-retinal pigment epithelial lesions. The second eye was involved 4 months later and there were new areas of hyper-reflective changes in both eyes, which migrated nasally within a week, with no evidence of scarring in the previous sites. The diagnosis of diffuse B-cell lymphoma was made on brain biopsy when the patient subsequently presented with acute confusion and magnetic resonance imaging brain scan showed a frontal lesion. Following systemic chemotherapy, the sub-retinal changes resolved with complete restoration of retinal architecture and improvement in visual acuity. CONCLUSION: We report an unusual case of PVRL presenting as migrating retinal lesions with unique shapes. PVRL is a great imitator and a high index of clinical suspicion is required in unexplained ocular lesions to prevent a delay in diagnosis.

Clinical Outcomes of Intravitreal Preservative-Free Triamcinolone Preparation (Triesence®) for Cystoid Macular Oedema and Inflammation in Patients with Uveitis.

PURPOSE: To assess the outcomes of intravitreal benzyl alcohol-free triamcinolone acetonide suspension in uveitis-related macular oedema. METHODS: Single-center retrospective cohort study of 66 injections to 44 eyes of 40 patients. Uveitis diagnosis, systemic and local therapy, intraocular pressure (IOP), central retinal thickness (CRT), number of injections, time to re-injection and side-effects were noted during 6-months minimum follow-up. RESULTS: Sixty eight percent of eyes received a single injection. 18% required 2 injections, and 13% received ≥3 injections with mean time to second and third injections of 25.5 and 52.7 weeks, respectively. 90% of injections were unilateral. Mean CRT reduced, and by 12-weeks visual acuity improvement >0.3logMar was achieved in 46%. Cataract progression (47%) and IOP>21 mmHg (45%) were the commonest adverse events. CONCLUSION: Preservative-free triamcinolone is an additional option for uveitis-related macular oedema, particularly in unilateral cases, with favorable CRT and visual outcomes. Repeat injections may be necessary, and the period of efficacy varies between eyes.

Adalimumab in refractory cystoid macular edema associated with birdshot chorioretinopathy.

PURPOSE: To report the clinical outcomes of adalimumab therapy in cases of birdshot chorioretinitis (BCR) with cystoid macular edema (CME) refractory to conventional immunotherapy. METHODS: This is a retrospective case series of three BCR patients treated with adalimumab for refractory CME. The main outcome measure was central subfield thickness (CST) on optical coherence tomography. Any patients treated with local steroids and/or receiving systemic steroids higher than 40 mg prednisolone daily during adalimumab therapy were excluded. RESULTS: At baseline, all patients were receiving systemic corticosteroids and two second-line immunosuppressive agents. The mean duration of treatment with adalimumab was 31.2 months (range 17.2-52). The mean CST was 327 ± 112.7 µm (mean ± SD) at baseline and 256.2 ± 39.7 µm at 6 months and 235.5 ± 32.5 µm at 12 months. Adalimumab permitted cessation or reduction in the daily dose of oral prednisolone plus withdrawal of a second-line agent in all patients. CONCLUSIONS: In these patients, adalimumab was effective in the treatment of refractory CME.

Full-thickness macular hole: a rare complication of Borrelia burgdorferi neuroretinitis.

Borrelia burgdorferi is a known infective cause of neuroretinitis. We present a case of B burgdorferi neuroretinitis complicated by macular hole in a 22-year-old man. The neuroretinitis was managed with early high-dose intravenous corticosteroid and oral antibiotic. The macular hole was managed with macular hole surgery after intraocular inflammation had resolved.

Multimodal Imaging in Acute Posterior Multifocal Placoid Pigment Epitheliopathy Demonstrating Obstruction of the Choriocapillaris.

Optical coherence tomography angiography (OCTA) provides noninvasive in vivo vascular imaging of the retina and choriocapillaris. To highlight OCTA utility, the authors align structural changes and their resolution with functional outcome. The authors present a case of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and sequential changes during transition to inactive disease. In the acute phase, altered flow and nonperfusion were seen in defined islands of choriocapillaris. Over time, progressive reperfusion was observed and accompanied clinical resolution and functional visual restoration. The imaging features acquired described the level of nonperfusion the authors had assumed when extrapolating findings from multiple independent imaging modalities. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:677-681.].

Real-time PCR using the 529†bp repeat element for the diagnosis of atypical ocular toxoplasmosis.

BACKGROUND: Ocular toxoplasmosis may present in atypical fashion, particularly in immunosuppressed patients, and PCR is an important diagnostic tool especially when differentiating from other infectious causes. METHODS: A descriptive case-series demonstrating the use of a novel real-time PCR protocol targeting 529 bp repeat element, a multicopy and highly conserved fragment, in Toxoplasma gondii genome. This was designed and established by our microbiology service following independent, external validation. RESULTS: Three immunosuppressed patients presenting to a tertiary uveitis referral centre with unilateral, severe, sight-threatening uveitis are described. One patient presented with a large focus of sight-threatening retinitis and occlusive vasculitis while on systemic immunosuppression with azathioprine and adalimumab for Crohn's disease. One patient with chronic lymphocytic leukaemia presented with severe posterior uveitis and total retinal detachment. Finally, the third patient presented with severe retinitis adjacent to the optic nerve and vitritis causing acute vision loss. HIV infection was subsequently identified. In all three cases, the cause of inflammation was not clear from clinical examination alone and prompt treatment was required to prevent permanent vision loss. Intraocular sampling and PCR testing was performed including testing for toxoplasmosis, herpesviruses and syphilis. CONCLUSIONS: The novel real-time PCR assay described is more sensitive than those targeting the Toxoplasma B1 gene owing to the higher number of repeats and highly conserved sequence level. This technique can be applied in clinical practice and provides a valuable tool for the rapid diagnosis of ocular toxoplasmosis.

Multifocal chorioretinitis with progressive subretinal fibrosis in a young child.

Progressive subretinal fibrosis with uveitis (PSFU) syndrome is a rare clinical entity presenting with multifocal granulomatous chorioretinitis and subsequently developing extensive subretinal fibrosis over weeks or months. Subretinal fibrosis affecting the macula may cause profound and permanent vision loss. We report the presentation and management of this condition in a child, to our knowledge, the youngest reported. The condition caused substantial visual loss and required high-dose systemic corticosteroid and immunosuppression with methotrexate and ciclosporin to control aggressive intraocular inflammation.

Late in-the-bag intraocular lens dislocation in patients with uveitis.

BACKGROUND: Late in-the-bag intraocular lens (IOL) dislocation is an unusual complication of cataract surgery, being strongly associated with pseudoexfoliation, less so with previous vitreoretinal surgery, myopia and uveitis. We present the clinical features, management and outcomes of late spontaneous IOL dislocation in a series of patients with uveitis. METHODS: A retrospective case series of IOL dislocation affecting patients in the Manchester Uveitis Clinic, UK. The uveitis diagnosis, IOL type, presentation and management are discussed. RESULTS: Six patients from out of 1056 undergoing cataract surgery (0.57%) were affected. Uveitis was the only identified risk factor for IOL dislocation, which occurred a mean 10.3 years following uncomplicated cataract surgery by phakoemulsification with endocapsular IOL implantation. The dislocation was in-the-bag in all six cases. Two patients presented with the IOL in the anterior chamber, and required removal of the IOL-bag complex, and are using aphakic refractive correction. Two patients with inferior IOL subluxation have been managed conservatively. Two patients underwent pars plana vitrectomy with sutureless scleral fixation of the existing IOL in one case, and IOL exchange with a scleral sutured IOL in the other. CONCLUSIONS: IOL dislocation is an uncommon late complication in patients with uveitis. Conservative management is appropriate in patients with tolerable symptoms, or in those with difficult uveitis. Otherwise, fixation of the existing IOL, or removal and implantation of a secondary IOL, may be necessary. Angle-supported, or iris-enclaved IOLs, are not of proven safety in this patient group; scleral-fixated posterior chamber IOLs are the favoured approach in our service.