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 mu m +/- 176, improving to 296 mu m +/- 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.

Purpose To demonstrate changes in the demography and diagnosis of uveitis in a specialist clinic in the United Kingdom. Methods Retrieval of data including all new referrals to Manchester Uveitis Clinic from 1991 to 2020. The incidence and proportions of diagnoses between 4 quartiles was compared. Results 5000 patients with uveitis were seen. Referral rates trebled over time. Highly significant increases in referrals were seen for multiple evanescent white dot syndrome-spectrum disorders, syphilis and tuberculosis; increases were also seen for herpetic retinitis, vitreoretinal lymphoma and sarcoidosis. Highly significant decreases were seen for Fuchs' uveitis, Behcet's uveitis and ocular toxoplasmosis. Conclusions Subspecialisation and de-skilling has changed referral patterns to specialist clinics; changes cannot be entirely attributed to disease incidences, which also vary between countries. International data are non-comparable. There are clear changes in referral patterns and disease incidence in this population, influenced by evolving diagnosis. Local data should steer care planning.

Purpose To describe practical approaches to the management of subluxed or dislocated intraocular lenses (IOL) in patients with uveitis. Patients and methods Retrospective case series from a specialist uveitis clinic Results Fifteen IOLs in 13 patients were subluxed inferiorly (12) or dislocated into anterior chamber (2) or vitreous (1) at a mean delay of 12 years after cataract surgery. Six eyes required vitrectomy and seven IOL explantation. A dislocated IOL was repositioned by scleral fixation in one, and a new IOL was implanted in three (two scleral-sutured, one iris-claw). Eight were observed without surgery and 7 were left functionally aphakic (4 corrected with contact lens). The mean final best-corrected visual acuity was 0.6 LogMAR. Conclusions There are several management choices for IOL dislocation which should take into account the degree of uveitis, patient age and expectations. We present a pragmatic approach: surgery can often be avoided in this high-risk group.

Purpose: Cytomegalovirus retinitis (CMVR) is a serious and potentially sight-threatening infection in immunocompromised individuals. Strategies for the management of drug-resistant CMVR are described. Methods: A case of severe bilateral CMVR in a single lung transplant patient, with UL97 mutation conferring ganciclovir-resistance, is presented. Treatment with standard antiviral agent and adjuvant leflunomide, immunosuppression modifications (calcineurin inhibitors and corticosteroid), intravitreal antiviral therapy and novel use of CMV-immunoglobulin is described. A literature review to support drug-resistant CMVR management is presented. Results: Severe and progressive CMV retinitis was refractory to intravitreal foscarnet and systemic leflunomide. Drug-toxicity restricted systemic antiviral therapy options. The use of combined leflunomide and CMV-immunoglobulins, in the absence of viremia, has not been previously reported. Loss of ganciclovir-resistance was eventually observed permitting successful treatment with systemic and intravitreal ganciclovir. Conclusions: Drug-resistant CMVR is a complex clinical challenge. Multiple systemic and local treatment strategies may be necessary but toxicity, resistance, and co-morbidities may severely restrict available options.

Background/aims There is a paucity of high-level evidence to support the management of childhood uveitis, particularly for those children without juvenile idiopathic arthritis uveitis (JIA). We undertook a modified Delphi consensus exercise to identify agreement in the management of chronic anterior uveitis (CAU), the most common manifestation of childhood disease. Methods A four-round, two-panel process was undertaken between June and December 2017. Paediatric uveitis specialists identified through multiple sources, including a multicentre network (the Paediatric Ocular Inflammation Group), were invited to participate. They were asked whether they agreed with items derived from existing guidelines on the management of JIA-U when extrapolated to the population of all children with CAU. Consensus was defined as agreement greater than or equal to 75% of respondents. Results 26 of the 38 (68%) invited specialists participated with the exercise, and response rates were 100% for rounds one to three, and 92% for round four. Consensus was reached on 23 of the 44 items. Items for which consensus was not reached included management at presentation, use of systemic and periocular steroids for children with severe disease and the role of conventional steroid sparing immunosuppressants beyond methotrexate. Conclusion The areas of management uncertainty at the level of the group, as indicated by absence of consensus, reflect the areas where the evidence base is particularly poor. Our findings identify the key areas for the future research needed to ensure better outcomes for this blinding childhood ocular inflammatory disorders.

Purpose: To report the detection of retinitis in the second eye of a patient with viral acute retinal necrosis (ARN), before the appearance of clinical change, using swept-source optical coherence tomography. Results: A 63 year-old male developed right-sided varicella-zoster virus (VZV) ARN, confirmed with aqueous sampling. High-dose intravenous aciclovir caused renal impairment and was suspended for two-days. One day later, left eye macular SS-OCT revealed focal retinal thickening and disruption of retinal architecture without clinically detectable retinitis. The patient was asymptomatic. Aqueous sampling was VZV PCR positive. He received bilateral foscarnet injections and renal adjusted dose of aciclovir. The left OCT signs improved with full restoration of retinal layers. Conclusions: We report for the first time the use of OCT to detect pre-clinical second eye retinitis during ARN. Prompt diagnosis and combined systemic and intensive local antiviral therapy resulted in a favourable structural and functional outcome.

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.

A 4-year-old girl presented with acute left visual loss 4 weeks after uneventful chickenpox. She was found to have left necrotising retinitis and profound retinal vasculitis and vitritis. Aqueous humour was PCR positive for varicella-zoster virus. Combined intravenous and intravitreal antiviral treatment led to rapid improvement with settled retinitis, no vascular occlusion and good recovery of vision. Her recent coinfection with Epstein-Barr virus may have acted to provoke the retinitis.

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.

An elderly lady with a history of T-cell pro-lymphocytic leukemia apparently successfully treated with alemtuzumab presented with unilateral intraocular inflammation masquerading as viral retinitis...

PurposeTo assess the incidence, clinical ocular involvement and effectiveness of anti-tuberculous treatment in patients with chronic uveitis presumed to be associated with tuberculosis in a non-endemic community.Patients and methodsRetrospective case series of patients with uveitis and evidence of tuberculosis, with no other identified cause of uveitis, who underwent a 6-month course of standard anti-tuberculosis treatment between 2008 and 2015. The response to treatment was assessed at 6 and 12 months after initiation of treatment.ResultsForty-eight patients were included of whom 36 (75%) were born outside the United Kingdom. Only five had concurrent active pulmonary or nodal tuberculosis. There were 85 affected eyes, including 25 with granulomatous anterior uveitis, 32 with retinal vasculitis (occlusive in 21), and 20 with multifocal choroiditis or serpiginous-like retinochoroiditis. Gamma-interferon testing was positive in 95%. Complete resolution at end point was seen in only 60%, but a further 19% were inflammation-free on topical steroid only. Resolution was lower (50%) in those with panuveitis compared to other anatomical types (75%). Sixty-four eyes (75%) had a LogMAR visual acuity of 0.1 or better at the end of the study.ConclusionsThe incidence of presumed tuberculosis-associated uveitis (TBU) has almost quadrupled in this region. The efficacy of treatment has not been enhanced by the introduction of gamma-interferon testing to support diagnosis. Some patients may require more prolonged antibiotic therapy to ensure quiescence, but chronic non-infective anterior uveitis may in any case follow treated TBU.

PurposeTo present the patient profiles, clinical presentations and visual outcomes in those diagnosed with ocular syphilis, attending a subspecialist uveitis service in northern England over a 15-year period.Patients and methodsRetrospective observational case series of patients presenting between January 2002 and December 2016.ResultsA total of 50 eyes of 34 patients had intraocular inflammation due to syphilis. Of these, 94% were male, and 75% were men who had sex with men. Ten (29%), all male, were HIV-positive. Presentations included isolated anterior non-granulomatous uveitis, intermediate uveitis, panuveitis, retinitis, placoid chorioretinitis and papillitis. Concurrent skin rash and/or headache were seen in 41%. Compliance with antibiotic treatment was complete, but there was a high rate of default from ophthalmological follow-up (38%). Visual improvement was seen in 92% of eyes, and at final assessment 71% had acuity of 6/9 or better.ConclusionsOcular syphilis is continuing to increase in incidence, in tandem with the continuing epidemic of early syphilis in the UK (the risk of ocular involvement being about 1%). Almost all are male, and most are men who have sex with men. Clinical presentation is variable; a high index of suspicion and a low threshold for serological testing is important; early treatment can reverse retinal changes and restore visual acuity.

PurposeTo quantify the additional information provided by ultra-widefield fluorescein angiography, compared with 7-field standard imaging, in patients with retinal vasculitis (RV).Patients and methodsRetrospective case series of 106 patients.ResultsRetinal vascular pathology was identified by UWF FFA, but not by standard ETDRS 7-field area, in 62 patients (58.5%) and in 79 eyes (43.4%). The pathology included active RV (47 eyes, 25.8% of eyes); retinal ischaemia, or infarction (53 eyes, 29.1%); and retinal neovascularization (7 eyes, 3.8%). A change to management was made in 36 patients (34%). Of these, 21 (20% of all patients undergoing angiography) were made after the identification of retinal vascular pathology, which was found only on UWF FFA, outside the ETDRS area.ConclusionUltra-widefield fluorescein angiography has clear advantages over standard multi-field imaging. It is currently the standard method of assessment for RV in this centre.

A 25-year-old woman presented with unilateral red eye and visual blur, and was found to have panuveitis with an inflammatory white mass at the macula, initially presumed to be Toxoplasma retinitis. After failure to respond, she underwent vitrectomy, which produced Candida albicans. Despite intraocular and systemic antifungal treatment, she lost all vision in that eye. Two years later, she developed unilateral hip osteomyelitis leading to total hip replacement and also revealing Candida infection. By clinical exome sequencing, she was then found to have caspase recruitment domain 9 (CARD9) deficiency, an autosomal recessive disorder that causes a specific susceptibility to candidal infections. She remains otherwise well but on lifelong fluconazole prophylaxis.

PURPOSE:To highlight the rare but life-threatening infective consequences of immunosuppression or biologic treatment for sight-threatening uveitis.PATIENTS AND METHODS:Retrospective case series of four immunosuppressed patients with uveitis complicated by sepsis.RESULTS:The affected patients were all treated using prednisolone 10 mg/day or greater, together with oral immunosuppression (2 mycophenolate mofetil, 1 azathioprine + ciclosporin, 1 methotrexate) and, in one case, infliximab. All patients survived following intensive treatment.CONCLUSION:Life-threatening infection is a rare but important risk in immunosuppressed patients with uveitis. Complete protection is not possible and prophylaxis regimens are of unproven efficacy. Patients should understand the risks before agreeing to a course of treatment.

Aims To investigate the hypothesis that lymphopenia is an independent predictor of sarcoidosis in new patients presenting with uveitis. Patients and methods Retrospective case–control study of 112 patients with sarcoidosis-associated uveitis (SAU) against 398 controls with other forms of uveitis. Results Of the patients with SAU, 30/112 (26.8%) had significant lymphopenia (<1.0×109/L), compared with 24/398 (6.0%) for other uveitis (p≤0.0001, OR 5.7 (95% CI 3.2 to 10.3)). The mean lymphocyte count for patients with SAU was 1.43 vs 2.04 for other uveitis (p≤0.0001). Logistic regression modelling using diagnosis of SAU as the independent variable identified age, ACE levels and lymphocyte count as independent predictors of SAU. A new patient with uveitis with significant lymphopenia has a risk of sarcoidosis (from this parameter alone) of 31.6%. Conclusions Significant lymphopenia (<1.0×109/L) is an independent predictor of sarcoidosis in new patients presenting with uveitis. We recommend that diagnostic criteria for SAU should be modified to include this phenomenon.

PURPOSE To describe pyogenic vertebral osteomyelitis as a rare infection associated with endogenous endophthalmitis.METHODS A retrospective review of three patients with endogenous endophthalmitis and sepsis due to underlying Staphylococcal vertebral osteomyelitis presenting during a 21-month time period. The ophthalmic and systemic features and management and outcomes are presented.RESULTS One patient developed unilateral endophthalmitis with cervical spine osteomyelitis, Staphylococcus aureus being isolated from blood cultures. The second presented with bilateral endophthalmitis with disseminated Methicillin-resistant S. aureus (MRSA) infection, with thoracic and lumbar discitis and para-spinal abscesses. MRSA was cultured from vitreous, blood, and synovial fluid. Both patients received prolonged courses of intravenous antibiotics. Intravitreal antibiotic therapy was used in the second patient. Excellent visual and systemic outcomes were achieved in both cases with no ocular complications. The third patient developed lumbar osteomyelitis following spinal surgery and presented with disseminated S. aureus sepsis including unilateral endogenous endophthalmitis. Despite systemic antibiotics and intensive care the patient died.CONCLUSIONS Endogenous endophthalmitis should be suspected in septic patients developing eye symptoms. Endogenous endophthalmitis with staphylococcal bone infection is a rare but serious condition. Osteomyelitis should be considered as an infective source in any such patient reporting bone pain or reduced spinal mobility. Prompt investigation and treatment can achieve favourable visual and systemic outcomes.

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.

Purpose: To demonstrate the manifestations and complications of uveitis, and their medical and surgical management, in a very large group of patients attending the Manchester Uveitis Clinic (MUC), a specialist uveitis clinic in the Northwest of England, UK.Methods: Retrospective retrieval of data on a computerized database incorporating all new referrals to MUC from 1991 to 2013.Results: A total of 3000 new patients with uveitis were seen during a 22-year period, of which 25.2% had a single acute episode, 13.6% had acute recurrent uveitis, 20.2% had chronic fluctuating uveitis, and 41.0% had chronic unremitting uveitis. The commonest complications were cataract (35% of patients), macular edema (20.5%), and glaucoma (19.5%). Oral steroids were required in 36% of patients, oral immunosuppression in 16%, and biologic treatment in 2%. Major intraocular surgery was required in 28%.Conclusions: Oral steroid usage is not an independent risk factor for cataract formation in patients with uveitis. Oral immunosuppression usage has increased 4-fold during this study period.