Uveitis and Scleritis as a Risk Factor for Mortality.

PURPOSE: Uveitis and scleritis may be caused by local or systemic infection, or associated with noninfectious systemic inflammatory autoimmune disease. This study explored the all-cause mortality following an individual's first presentation with uveitis/scleritis. METHODS: A cross-sectional study was conducted on all uveitis/scleritis patients diagnosed by uveitis specialists and treated in a single tertiary referral center in New Zealand between 2006 and 2020(15y). Masquerade syndromes including intraocular lymphoma were excluded. Outcome measures: demographics, etiology of uveitis/scleritis, anatomical location and all-cause mortality. RESULTS: 2723 subjects were identified. Median age of onset of uveitis/scleritis was 44.9 years (Range:1.5-99.5 years). 49.6% were female. Median follow-up from diagnosis of uveitis/scleritis was 8.0 years (IQR 4.1-11.6 years) with a total follow-up of 24 443.3 subject-years. The most frequent diagnosis was idiopathic disease (30.9%), HLA-B27-positive uveitis (20.0%), and sarcoidosis (4.7%). Infectious etiologies (24.1%) were most commonly from herpes zoster virus (9.3%) and toxoplasmosis (4.3%). The age-adjusted mortality rate was higher in subjects with idiopathic disease, sarcoidosis, Fuchs' uveitis syndrome, granulomatosis with polyangiitis/ANCA-associated vasculitis, toxoplasmosis, and herpes zoster virus, when compared to HLA-B27-positive uveitis. Hazard of mortality peaked in the first seven years following diagnosis, then subsequently declined. Patients with uveitis/scleritis had a significantly higher rate of mortality compared to the general New Zealand population (IRR 1.656 p = 0.017). CONCLUSION: Infectious etiologies of uveitis/scleritis in this cohort were high when compared to other developed nations, attributable to data from a tertiary referral center treating inpatients. Potential shared inflammatory mechanisms in the eye and other organs can lead to concurrent non-ocular disease requiring systemic treatment, impacting an individual's longevity.

Insights into the diagnosis and management of sarcoid uveitis: A review.

Sarcoidosis is a leading cause of non-infectious uveitis that commonly affects middle-aged individuals and has a female preponderance. The disease demonstrates age, sex and ethnic differences in clinical manifestations. A diagnosis of sarcoidosis is made based on a compatible clinical presentation, supporting investigations and histologic evidence of non-caseating granulomas, although biopsy is not always possible. Multimodal imaging with widefield fundus photography, optical coherence tomography and angiography can help in the diagnosis of sarcoid uveitis and in the monitoring of treatment response. Corticosteroid remains the mainstay of treatment; chronic inflammation requires steroid-sparing immunosuppression. Features on multimodal imaging such as vascular leakage may provide prognostic indicators of outcome. Female gender, prolonged and severe uveitis, and posterior involving uveitis are associated with poorer visual outcomes.

Acute posterior multifocal placoid pigment epitheliopathy: clinical presentation and risk of stroke and transient ischaemic attack.

BACKGROUND/AIMS: Acute posterior multifocal placoid pigment epitheliopathy is a rare but important disease that can be associated with life-threatening complications due to cerebral vasculitis. The primary objective was to determine the incidence of neurological complications and risk factors for stroke and transient ischaemic attack (TIA) associated with acute posterior multifocal placoid pigment epitheliopathy. Secondary objectives included the clinical presentation, visual outcomes and recurrence rates. METHODS: This was a multicentre retrospective case series including 111 eyes from 60 subjects presenting from January 2009 to June 2020. RESULTS: Median age at presentation was 29 years (IQR 24.7-35.1) and 36 subjects (60.0%) were male. 20 subjects (33.3%) reported a viral prodrome. Stroke and TIA were observed in seven subjects (11.7%). Older age was the only significant risk factor for stroke/TIA (p=0.042). Vision loss occurred in seven eyes, with four eyes (3.6%) having final visual acuity 6/15-6/60 and three eyes (2.7%) having visual acuity of 6/60 or worse. Recurrence occurred in 10 subjects (16.7%). CONCLUSIONS: The presence of headache cannot reliably predict those at risk of stroke/TIA. Individuals presenting with acute posterior multifocal pigment epitheliopathy should therefore undergo a clinical neurological review and work-up for cerebral vasculitis as deemed appropriate by the treating ophthalmologist and collaborating neurologist.

The spectrum of paediatric uveitis in New Zealand.

AIMS: To describe the aetiology, complications, treatment and outcomes of paediatric uveitis. METHODS: This was a retrospective chart review including all paediatric participants presenting with uveitis to a tertiary referral hospital in Auckland, New Zealand between January 1997 and March 2020. RESULTS: Two hundred and twenty-four eyes of 143 participants were included. One hundred and three (46.0%) eyes were found to have uveitis without the child reporting any symptoms. Non-infectious uveitis occurred in 97 (67.8%) participants and infectious aetiology occurred in 46 (32.2%) participants. One hundred and twenty-six (56.3%) eyes developed complications by final follow-up, including ocular hypertension (60 eyes, 26.8%), cataract (55 eyes, 24.6%) and glaucoma (21 eyes, 9.4%). Conventional disease modifying anti-rheumatic drugs (DMARDs) were required in 58 (59.8%) participants, and biologic disease modifying anti-rheumatic drugs in 31 (32.0%) participants with non-infectious uveitis. Participants who were younger at presentation were more likely to require a DMARD (OR 0.896 p=0.032). Vision loss of 6/15 or worse occurred in 38 (17.0%) eyes. CONCLUSIONS: Infections are an important cause of uveitis in this age group. Asymptomatic presentation and complications commonly occur. A large proportion of children with non-infectious uveitis will require steroid sparing immunosuppression.

Long term outcome and prognostic indicators in Posner Schlossman syndrome.

BACKGROUND: Posner Schlossman syndrome is a well-defined uveitis entity that is characterised by relapsing remitting unilateral anterior uveitis with markedly raised intraocular pressure. The aim of this study was to determine the risk factors for progression in patients with Posner Schlossman syndrome. METHODS: Ninety-eight patients were enrolled in a retrospective case series. Progression was defined as a composite endpoint of any of development of permanent glaucoma (in patients with no evidence of glaucomatous loss on presentation), corneal failure, or chronic inflammation. Relapse was defined as a resolving episode of inflammation not meeting the criteria for progression. RESULTS: Seventy seven percent of patients relapsed on average each 2.2 years. Forty percent of patients progressed. On univariate analysis, increased age at enrolment, immunocompromise at enrolment, the presence of glaucomatous optic neuropathy at enrolment, the performance of an anterior chamber tap and a positive anterior chamber tap were all associated with increased risk of progression. On multivariate analysis, age at enrolment, immunocompromise at enrolment, the performance of an anterior chamber tap, and the presence of glaucomatous optic neuropathy at enrolment were independently associated with increased risk of disease progression. CONCLUSIONS: Posner Schlossman syndrome is not a benign uveitis entity and risk of both relapse and progression are high. Older patients, immunocompromised patients, patients with glaucomatous optic neuropathy at enrolment and those with a positive anterior chamber tap are all at increased risk of progression.

Idiopathic Retinal Vasculitis, Aneurysms and Neuroretinitis: Clinical Improvement with Infliximab.

PURPOSE: Idiopathic retinal vasculitis, aneurysms and neuroretinitis is a rare vision-threatening condition. If untreated vision loss occurs due to complications of progressive retinal ischaemia including retinal neovascularisation, neovascular glaucoma and retinal exudation. Despite the proposed underlying inflammatory aetiology this condition demonstrates poor response to corticosteroid treatment. The aim was to describe two paediatric cases of idiopathic retinal vasculitis, aneurysms and neuroretinitis treated with infliximab. METHODS: Two case reports. RESULTS: Infliximab treatment led to resolution of aneurysmal dilatations and retinal vasculitis, and reversal of some retinal capillary non-perfusion. CONCLUSION: Early infliximab treatment should be considered in cases of idiopathic retinal vasculitis, aneurysms and neuroretinitis.

Review of de novo uveitis in older adults presenting to a large tertiary centre.

BACKGROUND/AIMS: The primary aim of this study was to describe the causes of de novo uveitis in individuals 60 years and older. Secondary objectives were to determine the incidence of intraocular lymphoma and the clinical predictors of lymphoma. METHODS: Retrospective chart review of all subjects presenting to the uveitis service at Auckland District Health Board (Auckland, New Zealand) between January 2006 and October 2020 RESULTS: 686 subjects (900 eyes) were aged ≥60 years at first presentation with uveitis, representing 23.4% of all subjects with uveitis during the study period. Non-infectious aetiology occurred in 631 (70.1%) eyes and infectious etiologies occurred in 269 (29.9%) eyes. The most frequent causes were idiopathic (36.3%), herpes zoster (14.8%), HLAB27 (8.7%) and sarcoidosis (4.8%). Twenty (2.2%) eyes of 13 (1.9%) subjects had a diagnosis of lymphoma. Lymphoma represented 11.2% of all intermediate uveitis. Subjects diagnosed with lymphoma did not develop posterior synechiae, epiretinal membrane, cystoid macular oedema or ocular hypertension. CONCLUSIONS: Intraocular lymphoma was uncommon in the overall cohort, but an important cause of intermediate uveitis. A diagnosis of lymphoma needs to be considered in any older subject with de novo intermediate uveitis. The lack of posterior synechiae, cystoid macular oedema, epiretinal membrane and ocular hypertension further increases the suspicion for lymphoma.

Endogenous Endophthalmitis: A 21-Year Review of Cases at a Tertiary Eye Care Centre.

PURPOSE: Endogenous endophthalmitis is rare and associated with significant morbidity and mortality. The primary objective was to identify causative organisms. Secondary objectives included the determination of systemic risk factors and visual prognostic factors. DESIGN: Retrospective review. METHODS: 78 eyes from 62 subjects over a 21-year period from 1999 to 2020 in Auckland, New Zealand. Parameters assessed included pathologic microbial organism, clinical presentation, treatment, complications, prognostic factors, and visual outcomes. METHODS: Information was collected on microbiology, treatment, visual outcomes, and complications. RESULTS: Median age was 61.6 years and 32 subjects (51.6%) were male. Diabetes was the most common risk factor seen in 24 (38.7%) subjects. 17 subjects (27.4%) presented directly to ophthalmology and 17.4% had an initial misdiagnosis. 49 subjects (79.0%) presented with reduced vision and only 27 (43.5%) presented with pain. Hypopyon was present in 13 eyes (16.7%). Gram-positive bacteria were the most common causative organism seen in 40 (51.3%) eyes, followed by yeast and fungi in 21 (26.9%) eyes, then gram-negative bacteria seen in 17 (21.8%) eyes. Median final BCVA was 6/18. Severe vision loss occurred in 33 (42.3%) eyes and 7 (9.0%) eyes required evisceration or enucleation. Presenting visual acuity was a significant predictor of visual outcome. CONCLUSION: Endogenous endophthalmitis occurred at 1.9 cases per million per year. Ophthalmologists require a high index of suspicion for underlying systemic infection in any subject presenting with ocular inflammation, and need to be aware that endogenous endophthalmitis may present without pain and frequently without hypopyon.

Drug-induced ocular inflammation.

AIM: Drug-induced ocular inflammation is rare and may be overlooked as a cause of uveitis. The main objective was to describe the causes of drug-induced ocular inflammation. Secondary objectives included uveitis complications and drug rechallenge reactions. METHODS: A retrospective chart review at Auckland District Health Board's tertiary uveitis clinic (Auckland, New Zealand) was performed. Participants were identified using the uveitis database, which consists of 2,750 subjects. Fifty eyes of 35 subjects had drug-induced inflammation. RESULTS: Drug-induced inflammation occurred in 1.3% of subjects with uveitis. Mean age was 66.8±15.6 years, and 25 subjects (71.4%) were female. Drugs responsible were bisphosphonates (24 subjects, 68.6%), brimonidine (one subject, 2.9%), etanercept (three subjects, 8.6%), immune checkpoint inhibitors (two subjects, 5.7%), BRAF inhibitors (three subjects, 8.6%), EGFR inhibitors (one subject, 2.9%) and allopurinol/perindopril (one subject, 2.9%). In subjects with bisphosphonate inflammation, anterior uveitis occurred in 22 (91.7%) and scleritis in two (8.3%). A positive rechallenge reaction occurred in two subjects with zoledronate and one with alendronate. Uveitis occurred in six subjects (17.1%) treated with cancer drugs including immune checkpoint inhibitors, BRAF inhibitors and EGFR protein kinase inhibitors. Subjects with cancer-drug-induced uveitis were managed with corticosteroids and five subjects were able to continue therapy; in one subject uveitis was uncontrollable and required drug cessation. CONCLUSIONS: Ocular inflammation caused by bisphosphonates is usually mild and resolves on medication withdrawal. Uveitis seen in association with newer cancer medications can be more severe, but in most cases it can be managed without medication cessation.

Nurse specialists for the administration of anti-vascular endothelial growth factor intravitreal injections.

AIM: The number of individuals with chronic conditions such as age-related macular degeneration (AMD) is increasing, and consequently the treatment burden for anti-vascular endothelial growth factor (anti-VEGF) intravitreal injections is also increasing. The use of nurse specialists to administer anti-VEGF intravitreal injections has been proposed to address this treatment burden. This was a prospective safety audit to determine the safety of nurse specialists for the delivery of anti-VEGF intravitreal injections. METHOD: A prospective safety audit was undertaken for a nurse specialist-delivered injection service in the Ophthalmology Clinic, Greenlane Clinical Centre. The department's senior medical retinal consultant supervised the nurse specialist training programme. The clinical safety of anti-VEGF intravitreal injections delivered by nurse specialists, and the impact of this programme on clinical capacity at our Institute was reviewed. RESULTS: The nurse specialists administered a total of 2,900 injections over an 18-month period. Two patients developed endophthalmitis post injection (1 infective, 1 non-infective). Two patients had a vitreous haemorrhage, and five patients had raised intraocular pressure. The incidence of post-injection endophthalmitis, vitreous haemorrhage and raised intraocular pressure was 0.07%, 0.07% and 0.17%, respectively. CONCLUSION: The nurse specialist-delivered injection service is a safe and effective service for treatment of wet AMD, diabetic macular oedema and vein occlusion.