The role of a multicentre data repository in ocular inflammation: The Ocular Autoimmune Systemic Inflammatory Infectious Study (OASIS).

In the current literature, clinical registry cohorts related to ocular inflammation are few and far between, and there are none involving multi-continental international data. Many existing registries comprise administrative databases, data related to specific uveitic diseases, or are designed to address a particular clinical problem. The existing data, although useful and serving their intended purposes, are segmented and may not be sufficiently robust to design prognostication tools or draw epidemiological conclusions in the field of uveitis and ocular inflammation. To solve this, we have developed the Ocular Autoimmune Systemic Inflammatory Infectious Study (OASIS) Clinical Registry. OASIS collects prospective and retrospective data on patients with all types of ocular inflammatory conditions from centers all around the world. It is a primarily web-based platform with alternative offline modes of access. A comprehensive set of clinical data ranging from demographics, past medical history, clinical presentation, working diagnosis to visual outcomes are collected over a range of time points. Additionally, clinical images such as optical coherence tomography, fundus fluorescein angiography and indocyanine green angiography studies may be uploaded. Through the capturing of diverse, well-structured, and clinically meaningful data in a simplified and consistent fashion, OASIS will deliver a comprehensive and well organized data set ripe for data analysis. The applications of the registry are numerous, and include performing epidemiological analysis, monitoring drug side effects, and studying treatment safety efficacy. Furthermore, the data compiled in OASIS will be used to develop new classification and diagnostic systems, as well as treatment and prognostication guidelines for uveitis.

Uveitis Registries - A Digital Tool for Patient Care, Education, Research, and Collaboration.

PURPOSE: Clinical registries are increasingly important in research and clinical advancement. This review explores and compares current uveitis registries and recommends future directions on how uveitis registries can complement one another for synergistic effect and benefit. METHODS: From a systematic search, 861 citations were screened for longitudinal, non-interventional, and multicenter uveitis-specific registries. Additional registries were identified via consultations with uveitis experts. Characteristics of all registries were analyzed and compared. RESULTS: Four registries were identified: Treatment Exit Options for Non-infectious Uveitis, AutoInflammatory Disease Alliance International Registry, Ocular Autoimmune Systemic Inflammatory Infectious Study, and Fight Uveitis Blindness!. Despite certain differences, these registries have the overarching goal of collecting large quantities of real-world, high-quality patient data to improve the understanding of uveitis. CONCLUSION: The four uveitis registries share similar goals and collect clinical data from overlapping geographical regions. There is vast potential for collaboration, including data sharing to further augment datasets for analysis.

Uveitis in Tumor Patients Treated with Immunological Checkpoint- and Signal Transduction Pathway-Inhibitors.

PURPOSE: New tumor therapies like immune checkpoint inhibitors and small molecule inhibitors of MEK and BRAF have increased the patient's survival rate but can be burdened with severe side-effects including uveitis. Here, we show the spectrum, treatment, and outcome of uveitis types induced by tumor treatment. METHODS: In this retrospective study, we have included 54 patients from different centers who were developing uveitis under tumor therapy. A 16-item questionnaire was analyzed for type, treatment, and outcome of uveitis and type of tumor treatment, which we have correlated here. RESULTS: Irrespective of the tumor treatment, most patients developed anterior uveitis. All patients received corticosteroids and some additional immunosuppressive treatments. Cessation of tumor therapy was necessary only in a minority of cases. CONCLUSIONS: Ocular autoimmunity should be differentiated from toxic effects of cancer treatment and timely recognized since it can be generally well controlled by anti-inflammatory treatment, preserving the patient's vision without cessation of the tumor treatment.

Infective Necrotizing Scleritis After XEN Gel Stent With Mitomycin-C.

PURPOSE: The purpose of this study was to report a case of infective necrotizing scleritis following XEN Gel Stent with mitomycin-C. METHODS: Case report. This is a case report of a 68-year-old woman. RESULTS: XEN Gel Stent glaucoma surgery enhanced with mitomycin-C 0.04% and combined with cataract surgery was performed at a regional center to manage the patient's primary open-angle glaucoma. Past medical history was significant for rheumatoid arthritis requiring treatment with methotrexate and adalimumab. Periocular pain and swelling developed 14 months after the initial operation, followed by a rapid deterioration of visual acuity to 20/60, intraocular pressure of 4 mm Hg, and worsening pain 5 months later. On initial presentation to Sydney Eye Hospital, 180 degrees of scleral necrosis was evident with a moderate anterior segment inflammatory reaction and a large temporal choroidal effusion due to hypotony. Empirical hourly topical ofloxacin and cephalothin 5% drops, with oral moxifloxacin, were initiated. Conjunctival swab grew Staphylococcus aureus and Staphylococcus lugdunensis. Significant clinical improvement occurred, but the XEN Gel Stent became exposed after 9 days of treatment with worsening hypotony. Urgent surgical revision was performed to remove the XEN Gel Stent and apply a tutoplast plug with overlying amniotic membrane graft. Intraocular pressure gradually improved over 6 weeks to 15 mm Hg with reversal of hypotonous changes, and visual acuity stabilized at 20/40. CONCLUSIONS: To our knowledge, this is the first reported case of necrotizing scleritis following XEN Gel Stent insertion. It is a reminder that infection should always be the primary differential diagnosis in patients with surgical-induced necrotizing scleritis.

Adalimumab in patients with vision-threatening uveitis: real-world clinical experience.

OBJECTIVES: Biologics are rapidly emerging as an effective vision saving addition to systemic uveitis therapy. The aim of this multicentre retrospective study is to review the outcomes of a large group of patients treated with adalimumab. METHODS: A retrospective chart review of patients with refractory non-infectious, active uveitis treated with adalimumab was conducted. The main outcome measures were ability to reduce prednisolone dose, ability to control uveitis, final visual acuity and time to treatment failure. RESULTS: Forty-six patients with uveitis, treated with adalimumab were included in the study. The most common anatomical uveitis phenotype was panuveitis (n=17, 37.0%). The most common diagnosis was idiopathic uveitis (n=19, 41.3%). At their latest review (mean: 4.46 years; median 4.40 years), 35 (76.1%) patients were able to discontinue corticosteroids, 11 (23.9%) patients were able to taper to <7.5 mg/day and only 1 (2.2%) patient required 10 mg of prednisone. The mean visual acuity at the latest follow-up of the worse eye was logarithm of the minimum angle of resolution (logMAR) 0.42 (SD 0.72), while the mean visual acuity of the better eye was logMAR 0.19 (SD 0.34). Of the 89 eyes, 21 (23.6%) eyes improved by at least 2 lines, 5 eyes (5.6%) deteriorated by ≥2 lines while vision was unchanged in the remaining 63 (70.8%) eyes. The time to recurrence was 1 in 12.47 person-years for adalimumab, with a 17.4% (8 patient) relapse rate. There were no serious adverse events. CONCLUSIONS: This study highlights the efficacy of adalimumab in patients with vision-threatening non-infectious uveitis, preserving vision and allowing reduction of corticosteroid dose.

Psychotropic Drug-Induced Glaucoma: A Practical Guide to Diagnosis and Management.

This article provides a practical review of the diagnosis and management of angle closure induced by psychotropic agents, including tricyclic antidepressants, antipsychotics and anticonvulsants. Selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, monoamine oxidase inhibitors and antipsychotics may trigger angle closure by influencing pupil configuration through adrenergic, anticholinergic, serotonergic or dopaminergic mechanisms. Patients with narrow iridocorneal angles are at risk, and these are more common in people with hypermetropia (near-sightedness), older people and individuals with an Asian background. These patients may benefit from a laser peripheral iridotomy, either prophylactically or to relieve an acute angle-closure episode. An idiosyncratic reaction to medications such as topiramate may lead to angle closure through an alternate mechanism, leading to a uveal effusion. Ophthalmological review may be considered prior to commencing medications in high-risk patients.

UVEITIS CAUSED BY TREATMENT FOR MALIGNANT MELANOMA: A CASE SERIES.

BACKGROUND/PURPOSE: To report the largest case series to date of uveitis occurring in association with immunomodulatory therapy for malignant melanoma. METHODS: A retrospective multicenter case review. Twenty-two patients with uveitis occurring in association with either immunotherapy or targeted immune therapy for malignant melanoma were identified. RESULTS: Of 22 patients, 11 had anterior uveitis in isolation. The remainder showed a variety of clinical features including panuveitis, ocular hypotony, papillitis, cystoid macular edema, and melanoma-associated retinopathy. Most patients responded well to treatment. CONCLUSION: We report the largest case series to date of patients with uveitis secondary to drug treatment for malignant melanoma. These cases are likely to increase in number in the future as newer immunomodulatory therapies for cancers are developed and the indications for these drugs increase. A dilemma arises when patients respond well to these drugs but develop vision-threatening side effects.

Development, Implementation, and Evaluation of Treatment Guidelines for Herpes Simplex Keratitis in Sydney, Australia.

PURPOSE: To develop and measure the uptake of a local guideline for herpes simplex keratitis (HSK) and to standardize initial antiviral therapy in Australia. METHODS: The Registered Nurses' Association of Ontario Toolkit: "Implementation of Best Practice Guidelines" was used to develop, implement, and evaluate the guideline at Sydney Eye Hospital. An implementation team was established to reach consensus on antiviral therapy guidelines through review of available evidence, identifying stakeholders, facilitators and barriers, creating strategies for implementation, and developing a sustainability plan. An audit of all adult HSK cases during a 6-month postguideline implementation period was conducted, and the results were compared with a preimplementation audit. A web-based survey was created to assess clinician awareness, usage, and level of knowledge of the guideline. RESULTS: Clinicians, pharmacists, and administrative staff were identified as stakeholders. Changing clinician's behavior was the major barrier to implementation. Implementation strategies included printed and online materials and lectures to clinicians. A postimplementation audit included 85 patients, and 95 clinicians received a web-based survey. The dose of the prescribed antiviral medication was in alignment with the local guideline in 80% (51/64) of the patients compared with 73% (163/223) before implementation (P = 0.331). Stromal HSK with ulceration and keratouveitis were excluded because there were no recommendations before implementation. Over 70% of clinicians (30/41) were aware of the guideline and accessed them through educational resources. CONCLUSIONS: Guidelines for the management of HSK may improve standardization of initial antiviral therapy in HSK. In practice, most clinicians were aware of and adhered to the local guideline.

Twenty-four-month outcomes of inflammatory choroidal neovascularisation treated with intravitreal anti-vascular endothelial growth factors: a comparison between two treatment regimens.

BACKGROUND AND AIM: There is still no established treatment regimen for eyes with inflammatory choroidal neovascularisation (iCNV) treated with intravitreal anti-vascular endothelial growth factor (VEGF) injections. This study compared the 24-month outcomes of two treatment regimens of anti-VEGF injections in eyes with iCNV. METHODS: Eyes with iCNV treated with anti-VEGF injections were divided into two groups: eyes treated with a loading phase of 3 monthly injections and then re-treated as needed (LOADING group) and eyes treated as needed from the beginning (PRN group). Visual acuity (VA), number of injections and iCNV recurrences at 24 months were compared between the groups. RESULTS: Eighty-two eyes were included, 42 in the LOADING and 40 in the PRN group. Baseline VA (mean(SD)) was 57.3 (15.8) letters in the LOADING vs 60.7 (15.6) letters in the PRN group (p=0.32). The VA (mean (95% CI)) increased at 3 months (+14.8 (10.6 to 18.9) and +11.2 (6.4 to 16) letters in the LOADING and PRN group, respectively) and remained significantly higher than baseline over the entire follow-up in both groups (all p<0.001). At 24 months, there was no difference in VA between the LOADING and PRN group (72.3 (14.0) vs 74.7 (11.3) letters, p=0.36) but the LOADING group received significantly more injections (median (Q1-Q3)) than the PRN (4.5 (3-7) vs 2.5 (2-3.2), p<0.0001). The iCNV recurrences were similar in both groups. CONCLUSIONS: iCNV responded well to anti-VEGF with significant and sustained VA improvement. The loading phase did not confer any advantage in terms of outcomes. PRN regimen from the beginning was as effective as more intensive treatment.

Post-surgical versus post-intravitreal injection endophthalmitis: changing patterns in causative flora.

IMPORTANCE: Endophthalmitis is a serious complication of intraocular procedures: knowledge of its causative organisms and outcomes may guide prevention and treatment. BACKGROUND: To determine the outcomes and spectrum of causative organisms in acute post-procedural endophthalmitis. DESIGN: A retrospective observational case series performed at a tertiary referral hospital during the period 1 July 2012 to 31 July 2017. PARTICIPANTS: Two hundred and forty-eight patients diagnosed with acute (≤ 6 weeks post-inciting event) endophthalmitis. METHODS: Chart review of microbiological and clinical data. MAIN OUTCOME MEASURES: The main outcome measure was odds of any improvement in visual acuity (3 months versus presentation). Secondary outcomes included causative organism, likelihood of vitrectomy and likelihood of evisceration. RESULTS: One hundred and ninty cases were post-cataract surgery or post-intravitreal injection (49 and 141, respectively). Causative organisms were identified in 45% of post-cataract surgery and 54% of post-injection cases (OR = 0.69; P = 0.61). Staphylococcus epidermidis was the most frequent causative organism. Streptococcus species accounted for 32% of post-surgical and 7% of culture-positive post-injection cases (OR = 6.63; P = 0.02). At 3 months, 81% of post-surgical and 84% of post-injection cases had improved BCVA over presentation (OR 0.59; P = 0.61). CONCLUSIONS AND RELEVANCE: S. epidermidis is the most common causative organism. In contrast to other studies, we did not find evidence for an increased odds of Streptococcus spp. endophthalmitis following intravitreal injection. This may in turn reflect guideline-driven changes in practice.

SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY FINDINGS IN ENDOGENOUS CANDIDA ENDOPHTHALMITIS AND THEIR CLINICAL RELEVANCE.

PURPOSE: To describe vitreal, retinal, and choroidal features of eyes affected by Endogenous candida endophthalmitis (ECE) analyzed by spectral domain optical coherence tomography (SD-OCT) and to evaluate their clinical impact. METHODS: Medical records and SD-OCT images from eyes diagnosed with ECE at four retina and uveitis tertiary referral centers were retrospectively evaluated. Spectral domain optical coherence tomography images were analyzed to evaluate the structural changes occurring in the vitreous, the retina, and the choroid in areas involved by ECE. Baseline and final best-corrected visual acuity were correlated with SD-OCT findings. RESULTS: Fifteen eyes from nine patients were enrolled. Vitreous involvement (vitreous cells, posterior hyaloid thickening) was detected in 13/15 eyes. Peculiar hyper-reflective preretinal aggregates obscuring the underlying retina because of a shadowing effect ("rain-cloud" sign) were noticed in all eyes with vitreous involvement. Two patterns of retinal and choroidal findings were identified: the first (six eyes) confined within the inner retinal layers (Intraretinal Pattern), the second (nine eyes) involving both retina (full thickness) and choriocapillaris (Chorioretinal Pattern). None of the eyes showed both patterns. None of the eyes, regardless the pattern, showed choroidal thickening. Baseline best-corrected visual acuity was not associated with OCT pattern (P = 0.09). On the contrary, final best-corrected visual acuity was significantly higher in patients showing Intraretinal Pattern (∼20/25, 0.06 ± 0.08 LogMAR) than in subjects with Chorioretinal Pattern (∼20/50, 0.44 ± 0.30 LogMAR) (P = 0.01). CONCLUSION: Endogenous candida endophthalmitis showed peculiar features on SD-OCT. Two distinct patterns of chorioretinal involvement influencing the final best-corrected visual acuity were identified. Spectral domain optical coherence tomography could be useful in the diagnosis, management, and outcome prediction in ECE.

NMNAT1 variants cause cone and cone-rod dystrophy.

Cone and cone-rod dystrophies (CD and CRD, respectively) are degenerative retinal diseases that predominantly affect the cone photoreceptors. The underlying disease gene is not known in approximately 75% of autosomal recessive cases. Variants in NMNAT1 cause a severe, early-onset retinal dystrophy called Leber congenital amaurosis (LCA). We report two patients where clinical phenotyping indicated diagnoses of CD and CRD, respectively. NMNAT1 variants were identified, with Case 1 showing an extremely rare homozygous variant c.[271G > A] p.(Glu91Lys) and Case 2 compound heterozygous variants c.[53 A > G];[769G > A] p.(Asn18Ser);(Glu257Lys). The detailed variant analysis, in combination with the observation of an associated macular atrophy phenotype, indicated that these variants were disease-causing. This report demonstrates that the variants in NMNAT1 may cause CD or CRD associated with macular atrophy. Genetic investigations of the patients with CD or CRD should include NMNAT1 in the genes examined.

Metallic Biomaterials: Current Challenges and Opportunities.

Metallic biomaterials are engineered systems designed to provide internal support to biological tissues and they are being used largely in joint replacements, dental implants, orthopaedic fixations and stents. Higher biomaterial usage is associated with an increased incidence of implant-related complications due to poor implant integration, inflammation, mechanical instability, necrosis and infections, and associated prolonged patient care, pain and loss of function. In this review, we will briefly explore major representatives of metallic biomaterials along with the key existing and emerging strategies for surface and bulk modification used to improve biointegration, mechanical strength and flexibility of biometals, and discuss their compatibility with the concept of 3D printing.

Normal tension glaucoma management: a survey of contemporary practice.

OBJECTIVE: The aim of this study was to investigate contemporary practice patterns with respect to normal tension glaucoma (NTG) management and to determine whether the 2 largest NTG trials have influenced ophthalmologists' clinical practice. METHODS: A survey questionnaire was sent to ophthalmologists via the American Glaucoma Society, the Canadian Glaucoma Society, and the Canadian Ophthalmological Society. The questionnaire was designed to investigate ophthalmologists' usual practice with respect to NTG and the extent to which practice has been influenced by the Collaborative Normal Tension Glaucoma Study (CNTGS) and the Low pressure Glaucoma Treatment Study (LoGTS). RESULTS: In total, 419 ophthalmologists completed the survey. Of these, 264 respondents were glaucoma subspecialists. The survey showed that 95% and 64% of ophthalmologists were familiar with the CNTGS and the LoGTS, respectively. Of the respondents, 70% indicated that they would initiate treatment in mild-to-moderate NTG without waiting for documented disease progression. Of the respondents, 61% of the total surveyed and 50% of the glaucoma subspecialists felt that the LoGTS results had no impact on their usual clinical practice. The first-choice topical drug for NTG was a prostaglandin analogue (88% of respondents) or brimonidine (10% of respondents). CONCLUSIONS: Most ophthalmologists treat NTG more aggressively than recommended by the CTNGS protocol. Most ophthalmologists felt that the LoGTS results had no impact on their normal clinical practice. The prostaglandin analogues are, by far, the most popular choice of drug for contemporary management of NTG.

Hypertensive eye disease: a review.

Hypertension is a risk factor for a number of vision-threatening eye conditions including retinal vascular occlusion, retinal macroaneurysm and non arteritic anterior ischaemic optic neuropathy. In addition, hypertension may exacerbate the vision-threatening effects of diabetic retinopathy and has been implicated in the pathogenesis of age-related macular degeneration. The effects of sustained hypertension are directly visible in the eye as hypertensive retinopathy and choroidopathy, reflecting a pathological process occurring throughout the body. Close collaboration between ophthalmologists and general practitioners/physicians is needed to ensure that hypertensive patients are identified and treated. Timely intervention in these patients may reduce the risk of both vision-threatening and systemic complications.