Neuro-ophthalmological manifestations of sarcoidosis.

Neuro-sarcoidosis has important ophthalmic and neuro-ophthalmic manifestations. Sarcoidosis most commonly affects the uveal tract (iris, ciliary body, and choroid) however the optic nerve is commonly involved. Sarcoid related optic neuritis is an important differential diagnosis in optic neuritis especially in atypical presentations. The use of multimodal imaging techniques available in the ophthalmic setting can enable the detection of choroidal or optic nerve granulomas and aid the diagnosis. Efferent manifestations of neuro-sarcoidosis are broad and can range from isolated cranial neuropathies or multiple as well as pupil abnormalities. Currently to date there are no diagnostic framework to assist in the diagnosis of ophthalmic manifestations in neuro-sarcoidosis in the absence of a tissue biopsy.

Impact on patient management of non-mydriatic fundus photography compared to direct ophthalmoscopy in a regional Australian emergency department.

OBJECTIVE: To investigate the management impact of non-mydriatic fundus photography (NMFP) implementation for appropriate ED patients; compare the diagnostic accuracy of direct ophthalmoscopy (DO) and NMFP, and determine the prevalence of fundus pathology in a regional Australian ED. METHODS: This before/after crossover study prospectively enrolled patients presenting with headache, neurological deficit, visual disturbance and/or hypertensive urgency. Patients received DO examination, then separate NMFP examination. Emergency clinicians (ECs) were surveyed on their patient management plans following both DO examination and NMFP imaging. Telemedicine review of NMFP images was performed by an ophthalmologist within 48 h, and any additional management changes were documented. RESULTS: The use of NMFP influenced changes in management in 52 (39%) of 133 enrolled patients (95% confidence interval 31-48%). Of these, 65% were escalations of management due to acute fundus pathology, while 35% were de-escalating changes following normal fundus findings. ECs diagnostic accuracy for acute fundus pathology improved from 0% to 29% sensitivity, and 59% to 84% specificity using DO and NMFP respectively, and telemedicine registrar review increased this to 50% sensitivity and 86% specificity. The period prevalence of acute fundus pathology was 10.5% (95% confidence interval 6-17%). CONCLUSION: The addition of NMFP images can significantly impact the management of ED patients requiring fundus examination, facilitating expedited and optimised patient care. NMFP improves ECs diagnostic acumen for fundus pathology over DO examination and telehealth specialist review is important for diagnostic accuracy. There is a clinically important prevalence of fundus pathology in this regional ED setting.

Endophthalmitis: Changes in Presentation, Management and the Role of Early Vitrectomy.

Endophthalmitis is a sight-threatening condition, and its timely and appropriate management is essential in preventing permanent vision loss. Recent changes in clinical practice in endophthalmitis and advances in modern vitreoretinal surgery may limit the applicability of established randomised clinical trial evidence to current management. This review discusses the epidemiology, pathophysiology, changing patient presentation, diagnosis and advances in the management of endophthalmitis, presenting the existing literature on this topic and results from Sydney Eye Hospital.

Intravitreal anti-vascular endothelial growth factor versus panretinal LASER photocoagulation for proliferative diabetic retinopathy: a systematic review and meta-analysis.

OBJECTIVE: To systematically review and perform a meta-analysis on the available evidence for anti-vascular endothelial growth factor (anti-VEGF) monotherapy versus panretinal photocoagulation (PRP) for proliferative diabetic retinopathy (PDR). DESIGN: Systematic review and meta-analysis PARTICIPANTS: Randomized clinical trials included participants ≥18 years old with clinical or angiographic evidence of PDR. Interventions included were anti-VEGF monotherapy and PRP. Excluded studies were those with potentially biased treatment allocation and those offering combination therapies. METHODS: The primary outcome was mean change in best-corrected visual acuity. Secondary outcomes were the proportion of patients developing severe (<6/60) or moderate (6/24-6/60) vision loss, rates of vitrectomy or vitreous hemorrhage, worsening macula edema, and reduced visual field indices. RESULTS: Five studies of varying quality met the inclusion criteria (n = 632). The anti-VEGF intervention arm had a mean difference of -0.08 logMAR or 4 Early Treatment Diabetic Retinopathy Study (EDTRS) letters gained (p = 0.02) when compared with PRP at 12 months. The difference in rates of vitrectomy and vitreous hemorrhage favoured anti-VEGF over PRP (risk difference [RD] -0.10, p = < 0.001 and RD -0.10, p = 0.003 respectively). CONCLUSIONS: This meta-analysis of the available evidence in patients with early PDR demonstrates a potential benefit for anti-VEGF over PRP alone. However, these benefits must be weighed against the relative costs of treatment and the potential risks of loss to follow-up.

Offline Learning with a Selection Hyper-Heuristic: An Application to Water Distribution Network Optimisation.

A sequence-based selection hyper-heuristic with online learning is used to optimise 12 water distribution networks of varying sizes. The hyper-heuristic results are compared with those produced by five multiobjective evolutionary algorithms. The comparison demonstrates that the hyper-heuristic is a computationally efficient alternative to a multiobjective evolutionary algorithm. An offline learning algorithm is used to enhance the optimisation performance of the hyper-heuristic. The optimisation results of the offline trained hyper-heuristic are analysed statistically, and a new offline learning methodology is proposed. The new methodology is evaluated, and shown to produce an improvement in performance on each of the 12 networks. Finally, it is demonstrated that offline learning can be usefully transferred from small, computationally inexpensive problems, to larger computationally expensive ones, and that the improvement in optimisation performance is statistically significant, with 99% confidence.

Ocular Toxoplasmosis in a Tertiary Referral Center in Sydney Australia-Clinical Features, Treatment, and Prognosis.

PURPOSE: The aim of this study was to provide a retrospective analysis of the presentation, demographics, and treatment regimens for ocular toxoplasmosis at a large tertiary referral uveitis center. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 48 patients with ocular toxoplasmosis who presented to Sydney Eye Hospital participated in this study. METHODS: This is a retrospective review of patient files who presented to Sydney Eye Hospital between 2007 and 2016 with clinical features consistent with ocular toxoplasmosis. Baseline risk factors and treatment details were recorded and analyzed. Main outcome measures were visual acuity and relapse rate compared with other studies in ocular toxoplasmosis. RESULTS: The median age was 35.5 (interquartile range 21-50) with 30 (60%) patients having no previous symptomatic episodes or evidence of chorioretinal scarring. Visual acuity at presentation was 0.51 or 6/19 (SE 0.096) and at follow-up 0.31 or 6/12 (SE 0.094). Nine patients experienced a recurrence during the period of observation with median time to recurrence 2.2 years (SE 0.45) and the relapse rate was 0.09/person-years. Location of lesion was predominantly within the vascular arcades (n = 44) with macular involvement in 9 patients. Most patients received clindamycin therapy (n = 34) with pyrimethamine and sulfadiazine was used for those with macula involvement. CONCLUSIONS: Patients with ocular toxoplasmosis had fewer recurrences compared with other published series and had better visual recovery. The majority of patients received clindamycin and oral prednisolone which were well tolerated with pyrimethazine and sulfadiazine reserved for those with macula-involving disease.

Optic Perineuritis Due to Tuberculosis.

A 30-year-old man experienced subacute peripheral visual field loss with preserved central vision in his right eye. He was diagnosed with optic perineuritis due to tuberculosis. Optic perineuritis is an uncommon disorder and, at times, can be difficult to distinguish from optic neuritis. The differentiation can have significant impact on diagnostic testing and patient management.

Adalimumab for the treatment of refractory active and inactive non-infectious uveitis.

BACKGROUND/AIMS: To compare the efficacy of adalimumab in eyes with active and inactive non-infectious uveitis in the real-world setting. METHODS: Multicentre, retrospective, chart review of patients with refractory non-infectious uveitis treated with adalimumab. Main outcome measures included reduction of prednisolone dose, ability to taper immunosuppressives and a composite endpoint of treatment failure encompassing active inflammatory chorioretinal or retinal vascular lesions, intraocular inflammation grade and visual acuity. RESULTS: Thirty-seven eyes of 22 patients were studied. Mean follow-up was 20.1 months (median: 13). Most had either posterior or panuveitis (n=12, 55%). Mean duration of uveitis at baseline was 83.2 months (median: 61), where the majority (n=15, 68%) had already been treated with two or more conventional immunosuppressive agents in addition to prednisolone. Oral prednisolone was reduced to ≤10 mg/day in 9 of 12 patients (75%) by 6 weeks. At 6 months of therapy, nine (90%) of the active eyes achieved a 2-step improvement in anterior chamber inflammation, with six (60%) demonstrating a similar improvement in vitreous haze grade. Almost all (n=17, 94%) of the initially inactive eyes maintained clinical quiescence at this time point. The incidence rate of treatment failure during follow-up was 88 per 100 eye-years for the active eyes and 24 per 100 eye-years for the initially inactive eyes. There were no serious adverse effects. CONCLUSION: Adalimumab appears to reduce the corticosteroid burden in active and inactive non-infectious uveitis in the real-world setting. Inflammatory activity at the time of adalimumab commencement may determine long-term treatment success.

Malignancy risk in patients with inflammatory eye disease treated with systemic immunosuppressive therapy: a tertiary referral cohort study.

OBJECTIVE: To ascertain whether patients on long-term systemic immunosuppressive therapy for inflammatory eye disease (IED) are at increased risk of malignancy. DESIGN: A single-center, retrospective cohort study. PARTICIPANTS: We included 190 adults with IED treated with corticosteroids only (n = 58) or systemic immunosuppression (n = 132) for ≥6 months between 1985 and 2007. Immunosuppressed patients were treated with antimetabolites, T-cell inhibitors, and/or alkylating agents. METHODS: Incident malignancies were ascertained by self-report and confirmed by medical record review. Multiple malignancies in a single patient were counted, except for nonmelanoma skin cancer (NMSC), where only the first was counted. Standardized incidence ratios (SIRs) were calculated by malignancy type. Cox regression models were used to compare malignancy incidence by treatment type. MAIN OUTCOME MEASURES: Risk of malignancy relative to the general population and within the cohort. RESULTS: During a median 7.34 years of follow-up, 25 malignancies were observed in 17 patients, namely, 2.10 per 100 person-years and 0.43 per 100 person-years in the immunosuppressed and corticosteroid only groups, respectively. In the immunosuppressed group, the most common malignancies were NMSC (n = 11) and non-Hodgkin's lymphoma (NHL; n = 4) and malignancy risk was significantly increased compared with the general population for any malignancy (SIR, 4.39; 95% CI, 2.78-6.59) and for any malignancy excluding NMSC (SIR, 4.16; 95% CI, 1.67-8.57). Significantly elevated SIRs were observed for NMSC and NHL in those treated with immunosuppressive agents. Compared with the corticosteroid treatment-only group, the immunosuppressed group was at an increased risk of any malignancy (adjusted hazard ratio, 4.36; 95% CI, 1.02-18.7), but not first malignancy (n = 17; adjusted hazard ratio, 2.56; 95% CI, 0.57-11.5). No cancer-related deaths were observed. CONCLUSIONS: Our findings suggest that patients with IED treated with systemic immunosuppressive therapy are at increased risk of malignancy; however, the increase in absolute risk was modest. The types of malignancies observed at excess risk are similar to those observed in solid organ transplant recipients and patients with autoimmune diseases treated with systemic immunosuppression. Immunosuppressive therapy remains an important treatment modality in IED; however, patients may benefit from targeted malignancy-prevention strategies and long-term clinical follow-up. These findings require validation by a prospective, long-term, population-based cohort study.

Are patients with inflammatory eye disease treated with systemic immunosuppressive therapy at increased risk of malignancy?

The purpose of this study is to review the literature on the risk of malignancy in patients with inflammatory eye disease (IED) treated with systemic immunosuppressive (IS) therapy. Relevant databases in transplant medicine, autoimmune diseases and literature regarding uveitis and scleritis were reviewed. Literature with regards systemic IS therapy in transplant recipients and patients with autoimmune diseases revealed a significant increase in malignancies, especially non-melanocytic skin cancers and lymphomas. Studies of patients with IED were limited in number and scope, with no studies adequately evaluating the incidence of malignancy in these patients. Difficulties associated with the evaluation of the risk of malignancy associated with IS therapy in patients with IED include the heterogeneity of the disease and treatment regimens as well as the low frequency of IED, its variable severity and the lack of adequate long-term follow-up studies. Systemic IS therapy is an important therapeutic option in the treatment of patients with severe IED. A well-designed, comprehensive, multi-centre long-term follow-up study is required to evaluate the risk of malignancy in patients with specific IED diseases treated with defined systemic IS therapy. Until such evidence is available, we recommend the adoption of preventative strategies to help minimise the risk of malignancy in such patients.