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The aim of this study was to determine the short-term compliance with regular home monitoring of macular retinal sensitivity (RS) in intermediate age-related macular degeneration (iAMD). Home-based outcomes were compared with in-clinic outcomes determined using (1) the same tablet device under supervision, and (2) the Macular Integrity Assessment (MaIA) microperimeter.Single-center longitudinal compliance and reliability study.A total of 73 participants with iAMD were trained to perform macular field testing with the Melbourne Rapid Fields-macular (MRF-m) iPad application. Volunteers were asked to return 6 weekly tests from home, guided by audio instructions. We determined compliance with weekly testing and surveyed for factors that limited compliance. Test reliability (false positive, false negative) and RS were compared to in-clinic assays (MaIA). Data are given as mean ± SD or as median [quartile 1-3 range]. Group comparisons were achieved with bootstrap to define the 95% confidence limits.A total of 59 participants submitted 6 home examinations with a median intertest interval of 8.0 [7.0-17] days. Compliance with weekly testing (7 days ±24 hours) was 55%. The main barrier to compliance was information technology (IT) logistic reasons. Of 694 home examinations submitted, 96% were reliable (false-positive results25%). The mean RS returned by the tablet was significantly higher (+3.2 dB, P.05) compared to the MaIA.Home monitoring produces reliable results that differ from in-clinic tests because of test design. This should not affect self-monitoring once an at-home baseline is established, but these differences will affect comparisons with in-clinic outcomes. Reasonable compliance with weekly testing was achieved. Improved IT support might lead to better compliance.

Background Prolonged-release fampridine (PR-FAM) 10-mg tablet twice daily is the only approved pharmacological treatment for improvement of walking ability in adults with multiple sclerosis (MS). LIBERATE assessed the safety/effectiveness of PR-FAM in the real-world. Objectives The aim of this study was to collect additional safety data, including the incidence rate of seizures and other adverse events (AEs) of interest, from patients with MS taking PR-FAM in routine clinical practice (including patients aged ≥ 65 years and those with pre-existing cardiovascular risk factors). Other objectives included change over time in patient-reported evaluation of physical and psychological impact of MS while taking PR-FAM, and change over time in physician-reported assessment of walking ability in MS patients taking PR-FAM. Methods Patients with MS newly prescribed PR-FAM were recruited (201 sites, 13 countries). Demographic/safety data were collected at enrolment through 12 months. Physician-rated Clinical Global Impression of Improvement (CGI-I) scores for walking ability, and Multiple Sclerosis Impact Scale-29 (MSIS-29) were assessed. Results Safety analysis included 4646 patients with 3534.8 patient-years of exposure; median (range) age, 52.6 (21–85) years, 87.3% < 65 years, and 65.7% women. Treatment-emergent AEs (TEAEs) were reported in 2448 (52.7%) patients, and serious TEAEs were reported in 279 (6.0%) patients, of whom 37 (< 1%) experienced treatment-emergent serious AEs (TESAEs) considered related to PR-FAM. AEs of special interest (AESI) occurred in 1799 (38.7%) patients, and serious AESI in 128 (2.8%) patients. Seventeen (< 1%) patients experienced actual events of seizure. Overall, 1158 (24.9%) patients discontinued treatment due to lack of efficacy. At 12 months, a greater proportion of patients on-treatment had improvement from baseline in CGI-I for walking ability versus those who discontinued (61% vs. 11%; p < 0.001). MSIS-29 physical impact score improved significantly for patients on-treatment for 12 months versus those who discontinued (mean change, baseline to 12 months: − 9.99 vs. − 0.34 points; p < 0.001). Results were similar for MSIS-29 psychological impact. Conclusion No new safety concerns were identified in this real-world study, suggesting that routine risk-minimization measures are effective. CGI-I and MSIS-29 scores after 12 months treatment with PR-FAM treatment show clinical benefits consistent with those previously reported. Trial Registration ClinicalTrials.gov: NCT01480063. Supplementary Information The online version contains supplementary material available at 10.1007/s40263-021-00840-x.

PURPOSE: To evaluate the 12-month outcomes of a novel posterior small incision sub-tenon ab interno technique of XEN stent insertion (‘Semi-open’). METHOD: Consecutive eyes underwent XEN stent insertion with the Semi-open technique by two surgeons between 1st July 2018 and 30th September 2019. All cases received subconjunctival injection of 0.1 mL of mitomycin C 0.2 mg/mL. Eyes with primary open angle glaucoma (OAG), secondary OAG or pseudophakic primary angle closure glaucoma (PACG) were included. Exclusion criteria were phakic PACG, uveitic or neovascular glaucoma and postoperative follow-up

PurposeTo investigate whether quantitative optical coherence tomography angiography (OCTA) metrics of the superficial/deep macular retina are associated with the development of visual field (VF) loss in the fellow eyes of normal tension glaucoma (NTG) patients with unilateral VF loss.MethodsA longitudinal study was conducted in which 61 eyes with normal VF (mean VF mean deviation −0.7±1.6 dB) from 61 NTG patients were included. All subjects underwent OCTA imaging, spectral-domain-OCT imaging and VF testing. OCTA metrics of superficial capillary plexus and deep capillary plexus (DCP) in the macular region were measured. Relationships between baseline OCTA metrics, demographics and ocular characteristics and the risk of VF glaucoma progression were analysed with a Cox proportional hazards model.ResultsDuring a mean follow-up of 38 months, 11 fellow eyes (18.0%) with normal VF at baseline were determined to have VF progression, while 21.3% of affected eyes had VF progression. After adjustment for potential confounding factors, decreased baseline DCP in the fellow eyes was significantly associated with future VF progression (HR 1.33, 95% CI 1.03 to 1.73, p=0.031).ConclusionDecreased DCP was associated with a higher risk of developing VF damage in NTG patients with unilateral VF loss. Assessments of DCP may help improve the evaluation of the risk of functional deterioration in fellow eyes with an initially normal VF.

Purpose This study examines the short-term uptake, compliance, and performance of a tablet device used for home monitoring of visual field (VF-Home) by glaucoma patients. Design Single-center, observational, longitudinal, compliance study. Methods Participants who were glaucoma suspects or had stable glaucoma in at least one eye were recruited during a regular clinic review. Baseline in-clinic visual field (VF) was recorded with the Humphrey Field Analyser (HFA, SITA standard) and repeated at 6 months. Participants were tasked with performing 6 VF examinations from home, at weekly intervals, using a loaned iPad tablet. Uptake was defined as returning at least 1 test from home. Reliability and global indices from VF-Home were compared to in-clinic outcomes. Data are shown as either mean ± [standard deviation] or median [quartile 1-3 range], and group comparisons were achieved with bootstrap. Results We recruited 186 eyes of 101 participants. VF-Home uptake was excellent, with 88% of participants successfully completing ≥1 home examination and 69% completing all 6 examinations. The median duration between tests was 7.0 [7.0-8.0] days. Barriers to uptake and compliance involved information technology (IT) logistical reasons, lack of motivation, or competing life demands. VF-Home gave greater fixation loss but a similar level of False Positives (FP) as the HFA. A high correlation was found for the mean defect between in-clinic and at-home outcomes (R = 0.85). Conclusions VF-Home can return a high level of short-term compliance and results comparable to those found by in-clinic testing. IT logistical reasons and lack of motivation are barriers to uptake and compliance.

Background: Treatment with natalizumab once every 4 weeks is approved for patients with relapsing-remitting multiple sclerosis, but is associated with a risk of progressive multifocal leukoencephalopathy. Switching to extended-interval dosing is associated with lower progressive multifocal leukoencephalopathy risk, but the efficacy of this approach is unclear. We aimed to assess the safety and efficacy of natalizumab once every 6 weeks compared with once every 4 weeks in patients with relapsing-remitting multiple sclerosis. Methods: We did a randomised, controlled, open-label, phase 3b trial (NOVA) at 89 multiple sclerosis centres across 11 countries in the Americas, Europe, and Western Pacific. Included participants were aged 18–60 years with relapsing-remitting multiple sclerosis and had been treated with intravenous natalizumab 300 mg once every 4 weeks with no relapses for at least 12 months before randomisation, with no missed doses in the previous 3 months. Participants were randomly assigned (1:1), using a randomisation sequence generated by the study funder and contract personnel with interactive response technology, to switch to natalizumab once every 6 weeks or continue with once every 4 weeks. The centralised MRI reader, independent neurology evaluation committee, site examining neurologists, site backup examining neurologists, and site examining technicians were masked to study group assignments. The primary endpoint was the number of new or newly enlarging T2 hyperintense lesions at week 72, assessed in all participants who received at least one dose of assigned treatment and had at least one postbaseline MRI, relapse, or neurological examination or efficacy assessment. Missing primary endpoint data were handled under prespecified primary and secondary estimands: the primary estimand included all data, regardless of whether participants remained on the assigned treatment; the secondary estimand classed all data obtained after treatment discontinuation or study withdrawal as missing. Safety was assessed in all participants who received at least one dose of study treatment. Study enrolment is closed and an open-label extension study is ongoing. This study is registered with EudraCT, 2018-002145-11, and ClinicalTrials.gov, NCT03689972. Findings: Between Dec 26, 2018, and Aug 30, 2019, 605 patients were assessed for eligibility and 499 were enrolled and assigned to receive natalizumab once every 6 weeks (n=251) or once every 4 weeks (n=248). After prespecified adjustments for missing data, mean numbers of new or newly enlarging T2 hyperintense lesions at week 72 were 0·20 (95% CI 0·07–0·63) in the once every 6 weeks group and 0·05 (0·01–0·22) in the once every 4 weeks group (mean lesion ratio 4·24 [95% CI 0·86–20·85]; p=0·076) under the primary estimand, and 0·31 (95% CI 0·12–0·82) and 0·06 (0·01–0·31; mean lesion ratio 4·93 [95% CI 1·05–23·20]; p=0·044) under the secondary estimand. Two participants in the once every 6 weeks group with extreme new or newly enlarging T2 hyperintense lesion numbers (≥25) contributed most of the excess lesions. Adverse events occurred in 194 (78%) of 250 participants in the once every 6 weeks group and 190 (77%) of 247 in the once every 4 weeks group, and serious adverse events occurred in 17 (7%) and 17 (7%), respectively. No deaths were reported. There was one case of asymptomatic progressive multifocal leukoencephalopathy (without clinical signs) in the once every 6 weeks group, and no cases in the once every 4 weeks group; 6 months after diagnosis, the participant was without increased disability and remained classified as asymptomatic. Interpretation: We found a numerical difference in the mean number of new or newly enlarging T2 hyperintense lesions at week 72 between the once every 6 weeks and once every 4 weeks groups, which reached significance under the secondary estimand, but interpretation of statistical differences (or absence thereof) is limited because disease activity in the once every 4 weeks group was lower than expected. The safety profiles of natalizumab once every 6 weeks and once every 4 weeks were similar. Although this trial was not powered to assess differences in risk of progressive multifocal leukoencephalopathy, the occurrence of the (asymptomatic) case underscores the importance of monitoring and risk factor consideration in all patients receiving natalizumab. Funding: Biogen.

Background: To determine the 12-month compliance with and retention of home monitoring (HM) with Melbourne Rapid Fields (MRFh) for patients with intermediate age-related macular degeneration (iAMD) and compare visual acuity (VA) and retinal sensitivity (RS) results to clinical measures. Methods: Participants were recruited to a 12-month HM study with weekly testing of vision with MRFh. Inclusion criteria were a diagnosis of iAMD, understand English instructions, VA ≥ 20/40, and access to an iPad. Supervised in-clinic testing of high contrast VA (HVA, ETDRS), low-luminance VA (LLVA, ETDRS with ND2 filter), and RS (Macular Integrity Assessment, MAIA, and MRF in-clinic, MRFc) was conducted every 6-months. Results: A total of 54 participants (67 ± 6.8 years) were enrolled. Compliance to weekly HM was 61% and study retention at 12-months was 50% of those with uptake (n = 46). No difference was observed between MRFc and MRFh across all RS and VA outcomes (p > 0.05). MRFh RS was higher than MAIA (29.1 vs. 27.1 dB, p < 0.001). MRFh HVA was not different from ETDRS (p = 0.08), but LLVA was 9 letters better (81.5 vs. 72.4 letters, p < 0.001). Conclusions: Over 12-months, MRFh yields a moderate level of compliance with (61%) and retention (50%) of weekly testing. Further studies are required to assess the ability of MRFh to detect early progression to nAMD.

Diagnosis of glaucoma requires more than the optic nerve head (ONH) evaluation findings alone, but ONH assessment is crucial to detection of glaucoma, assessment of severity, and monitoring for disease progression. Objective assessment of the ONH must be done independent of other clinical features. This chapter explores the process of examining the disc for glaucoma, where errors may occur, and strategies to avoid them.

Computed perimetry remains the gold standard of visual field measurement among glaucoma patients. However, several emerging technologies, made possible by advances in computer programming, smartphone, tablet, or virtual reality, allow alternative means of visual function assessment. These new visual tests may one day have a useful complementary role in visual field testing and to bridge the gap between perimetry and daily experience. Many of these emerging technologies have distinct practical advantages over Ganzfield bowl-based computed perimetry. This paper outlines a discussion of some of these emerging techniques in visual function assessment in glaucoma. How to cite this article Skalicky SE, Kong GYX. Novel Means of Clinical Visual Function Testing among Glaucoma Patients, Including Virtual Reality. J Curr Glaucoma Pract 2019;13(3):83–87.

The conventional stimulus for standard automated perimetry is fixed in size, giving elevated contrast thresholds and reduced test reliability in the periphery. Here, we test the hypothesis that appropriate scaling of the size of perimetric stimuli will return fixed thresholds and reduced variability across the visual field. We derived frequency-of-seeing (FOS) curves in five healthy subjects at central (3 degrees) and peripheral (27 degrees) locations with a method of constant stimuli (MOCS) using a desktop LCD display. FOS curves for a Goldmann III (GIII) stimulus were compared with those for size scaled spots. To consider clinical translation, we tested a further five healthy subjects (22-24 years) with the Melbourne Rapid Fields (MRF) tablet perimeter at several locations spanning 1 degree to 25 degrees from fixation, deriving FOS curves (MOCS) and also conducting repeated adaptive clinical thresholding to assess intra- and interobserver variability. We found that GIII contrast thresholds were significantly elevated in the periphery compared with the parafovea, with concomitant reduction of FOS slope. Using appropriately size scaled spots, threshold and slope differences between these locations were significantly reduced. FOS data collected with the tablet perimeter confirmed that size scaling confers broad equivalence of the shape of the FOS curve across the visual field. Repeated adaptive thresholding with size scaled stimuli gave relatively constant intra-observer variability across the visual field, which compares favorably with published normative data obtained with the GIII stimulus. The reduced variability will improve signal-to-noise ratio for correct classification of normal visual field test results, whereas the lower contrast thresholds yield greater dynamic range, which should improve the ability to reliably monitor moderate defects.

Background The refractive outcomes of glaucoma surgeries, particularly their effect on astigmatism, are incompletely understood. Main body Trabeculectomy is associated with a considerable amount of with-the-rule astigmatic change in the immediate postoperative period. This is followed by a gradual against-the-rule shift. These changes are altered with the use of mitomycin C (MMC). Non-penetrating surgery such as deep sclerectomy is also associated with a similar or smaller degree of induced astigmatism. Minimally invasive glaucoma surgery appears to be astigmatically neutral. There is no clear evidence regarding refractive outcomes of glaucoma drainage device surgery. Conclusions Induced astigmatism may account for a reduction in unaided visual acuity in the early postoperative period following a successful trabeculectomy. These changes appear to stabilise at 3 months, and it would be prudent to defer the prescription of new glasses until this time. If sequential cataract surgery is to be performed, toric intraocular lenses can be a useful option for astigmatic correction.

Purpose: To report here a case of uncontrolled glaucoma during third-trimester of pregnancy that was treated successfully with bilateral Xen gel stent insertion. Observations: A 35-year-old woman presented during the third trimester of pregnancy with bilateral uncontrolled primary open angle glaucoma. Her disc examination and visual fields were consistent with advanced glaucoma. After failed Selective Laser Trabeculoplasty and maximal medical treatment, including Acetazolamide, she was treated with bilateral consecutive Xen stent surgery with successful control of her intraocular pressure. Conclusions and Importance: The use of Xen implant may have advantages over traditional trabeculectomy, especially during pregnancy, as the procedure is shorter, with less dependence on on-table antimetabolite and being minimally invasive with sparing of the conjunctiva. Keywords: Xen gel stent, Glaucoma in pregnancy

Importance This study provides ophthalmologists who manage uveitic glaucoma with important information on factors that can affect the success of surgical management of this challenging disease. Background This study examines surgical outcomes of trabeculectomy and glaucoma device implant (GDI) surgery for uveitic glaucoma, in particular the effect of uveitis activity on surgical outcomes. Design Retrospective chart review at a tertiary institution. Samples 82 cases with uveitic glaucoma (54 trabeculectomies, 28 GDI surgeries) performed between 1 December 2006 and 30 November 2014. Methods Associations of factors with surgical outcomes were examined using univariate and multivariate analysis. Main Outcome Measures Surgical outcomes (failure, success and qualified success) as defined in Guidelines from World Glaucoma Association. Results Average follow up was 26.4 ± 21.5 months. Anterior uveitis was the most common uveitis type. Overall qualified success rate of the trabeculectomies was not statistically different to GDI, being 67% and 75% respectively (P = 0.60). Primary GDI and secondary GDI operations showed similar success rates. The most common post-operative complication was hypotony (~30%). Two cases of GDI developed endophthalmitis and none in trabeculectomies. Active uveitis at the time of operation was higher in trabeculectomy compared to GDI group (35% vs. 14%). Active uveitis at the time of surgery did not significantly increase risk of failure for trabeculectomies. Recurrence of uveitis was significantly associated with surgical failure in trabeculectomy group (odds ratio OR 4.8, P = 0.02) but not in GDI group. Conclusions and Relevance Surgical success rate of GDI was not significantly different to trabeculectomy for uveitic glaucoma in this study. Regular monitoring, early and prolonged intensive treatment of ocular inflammation is important for surgical success particularly following trabeculectomy.

We report a case series of three patients with previous trabeculectomies who developed elevated intraocular pressure (IOP) in the immediate postoperative period after routine Descemet stripping automated endothelial keratoplasty (DSAEK). All patients had functioning trabeculectomies preoperatively, and developed elevated IOP between 41 and 69 mm Hg within 24 hours following DSAEK surgery. The IOP was successfully controlled in all patients with topical IOP-lowering medications and oral acetazolamide, with the addition of ocular massage and release of aqueous for two patients. Thereafter, all patients maintained well-controlled IOPs. Patients with trabeculectomies should be followed-up closely immediately after DSAEK to monitor for raised IOP. The mechanism for this pressure rise is uncertain, but may involve air in the trabeculectomy sclerostomy or bleb resulting in blockage of aqueous flow. How to cite this article: Sheales MPH, Chan E, Ang GS, Kong YXG. Elevated Intraocular Pressure after Descemet Stripping Automated Endothelial Keratoplasty in Patients with a Trabeculectomy: A Case Series. J Curr Glaucoma Pract 2015;9(3):100-103.

PURPOSE: To establish the medium-term repeatability of the iPad perimetry app Melbourne Rapid Fields (MRF) compared to Humphrey Field Analyzer (HFA) 24-2 SITA-standard and SITA-fast programs. DESIGN: Multicenter longitudinal observational clinical study. METHODS: Sixty patients (stable glaucoma/ocular hypertension/glaucoma suspects) were recruited into a 6-month longitudinal clinical study with visits planned at baseline and at 2, 4, and 6 months. At each visit patients undertook visual field assessment using the MRF perimetry application and either HFA SITA-fast (n = 21) or SITA-standard (n = 39). The primary outcome measure was the association and repeatability of mean deviation (MD) for the MRF and HFA tests. Secondary measures were the point-wise threshold and repeatability for each test, as well as test time. RESULTS: MRF was similar to SITA-fast in speed and significantly faster than SITA-standard (MRF 4.6 ± 0.1 minutes vs SITA-fast 4.3 ± 0.2 minutes vs SITA-standard 6.2 ± 0.1 minutes, P < .001). Intraclass correlation coefficients (ICC) between MRF and SITA-fast for MD at the 4 visits ranged from 0.71 to 0.88. ICC values between MRF and SITA-standard for MD ranged from 0.81 to 0.90. Repeatability of MRF MD outcomes was excellent, with ICC for baseline and the 6-month visit being 0.98 (95% confidence interval: 0.96-0.99). In comparison, ICC at 6-month retest for SITA-fast was 0.95 and SITA-standard 0.93. Fewer points changed with the MRF, although for those that did, the MRF gave greater point-wise variability than did the SITA tests. CONCLUSIONS: MRF correlated strongly with HFA across 4 visits over a 6-month period, and has good test-retest reliability. MRF is suitable for monitoring visual fields in settings where conventional perimetry is not readily accessible.

Purpose To evaluate the use of smartphone-based virtual reality to objectively assess activity limitation in glaucoma. Methods Cross-sectional study of 93 patients (54 mild, 22 moderate, 17 severe glaucoma). Sociodemographics, visual parameters, Glaucoma Activity Limitation-9 and Visual Function Questionnaire - Utility Index (VFQ-UI) were collected. Mean age was 67.4 ± 13.2 years; 52.7% were male; 65.6% were driving. A smartphone placed inside virtual reality goggles was used to administer the Virtual Reality Glaucoma Visual Function Test (VR-GVFT) to participants, consisting of three parts: stationary, moving ball, driving. Rasch analysis and classical validity tests were conducted to assess performance of VR-GVFT. Results Twenty-four of 28 stationary test items showed acceptable fit to the Rasch model (person separation 3.02, targeting 0). Eleven of 12 moving ball test items showed acceptable fit (person separation 3.05, targeting 0). No driving test items showed acceptable fit. Stationary test person scores showed good criterion validity, differentiating between glaucoma severity groups (P = 0.014); modest convergence validity, with mild to moderate correlation with VFQ-UI, better eye (BE) mean deviation, BE pattern deviation, BE central scotoma, worse eye (WE) visual acuity, and contrast sensitivity (CS) in both eyes (R = 0.243-0.381); and suboptimal divergent validity. Multivariate analysis showed that lower WE CS (P = 0.044) and greater age (P = 0.009) were associated with worse stationary test person scores. Conclusions Smartphone-based virtual reality may be a portable objective simulation test of activity limitation related to glaucomatous visual loss. Translational relevance The use of simulated virtual environments could help better understand the activity limitations that affect patients with glaucoma.

Background In the assessment of a pituitary mass, objective visual field testing represents a valuable means of evaluating mass effect, and thus in deciding whether surgical management is warranted. Case presentation In this vignette, we describe a 73 year-old lady who presented with a three-week history of frontal headache, and ‘blurriness’ in the left side of her vision, due to a WHO grade III anaplastic haemangiopericytoma compressing the optic chiasm. We report how timely investigations, including an iPad-based visual field test (Melbourne Rapid Field, (MRF)) conducted at the bedside aided swift and appropriate management of the patient. Conclusions We envisage such a test having a role in assessing bed-bound patients in hospital where access to formal visual field testing is difficult, or indeed in rapid testing of visual fields at the bedside to screen for post-operative complications, such as haematoma.

The exponential distribution is frequently used to model the survival time of a patient population, which assumes the hazard rate to be a constant over time. This assumption is often violated as the hazard function may vary over time and exhibit one or more change points in its values. Several methods exist in the literature for detecting a single change point in a piecewise constant hazard function for right-censored data. A sequential testing approach to detecting multiple change points in the hazard function using likelihood ratio statistics and resampling is proposed, which is applicable to both right-censored and interval-censored data. Numerical results based on simulated survival data and a real example show that the proposed approach can accurately detect the change points in the hazard function for both right-censored and interval-censored data.

Purpose To evaluate the accuracy and efficiency of Visual Fields Easy (VFE), a free iPad app, for performing suprathreshold perimetric screening. Design Prospective, cross-sectional validation study. Methods We performed screening visual fields using a calibrated iPad 2 with the VFE application on 206 subjects (411 eyes): 210 normal (NL), 183 glaucoma (GL), and 18 diabetic retinopathy (DR) at Tilganga Institute of Ophthalmology, Kathmandu, Nepal. We correlated the results with a Humphrey Field Analyzer using 24-2 SITA Standard tests on 373 of these eyes (198 NL, 160 GL, 15 DR). Results The number of missed locations on the VFE correlated with mean deviation (MD, r = 0.79), pattern standard deviation (PSD, r = 0.60), and number of locations that were worse than the 95% confidence limits for total deviation (r = 0.51) and pattern deviation (r = 0.68) using SITA Standard. iPad suprathreshold perimetry was able to detect most visual field deficits with moderate (MD of −6 to −12 dB) and advanced (MD worse than −12 dB) loss, but had greater difficulty in detecting early (MD better than −6 dB) loss, primarily owing to an elevated false-positive response rate. The average time to perform the Visual Fields Easy test was 3 minutes, 18 seconds (standard deviation = 16.88 seconds). Discussion The Visual Fields Easy test procedure is a portable, fast, effective procedure for detecting moderate and advanced visual field loss. Improvements are currently underway to monitor eye and head tracking during testing, reduce testing time, improve performance, and eliminate the need to touch the video screen surface.

This study provides ophthalmologists who manage uveitic glaucoma with important information on factors that can affect the success of surgical management of this challenging disease.This study examines surgical outcomes of trabeculectomy and glaucoma device implant (GDI) surgery for uveitic glaucoma, in particular the effect of uveitis activity on surgical outcomes.Retrospective chart review at a tertiary institution.Eighty-two cases with uveitic glaucoma (54 trabeculectomies and 28 (GDI) surgeries) performed between 1 December 2006 and 30 November 2014.Associations of factors with surgical outcomes were examined using univariate and multivariate analysis.Surgical outcomes as defined in Guidelines from World Glaucoma Association.Average follow up was 26.4 ± 21.5 months. Overall qualified success rate of the trabeculectomies was not statistically different from GDI, being 67% and 75%, respectively (P = 0.60). Primary and secondary GDI operations showed similar success rates. The most common postoperative complication was hypotony (~30%). Active uveitis at the time of operation was higher in trabeculectomy compared with GDI group (35% vs. 14%). Active uveitis at the time of surgery did not significantly increase risk of failure for trabeculectomies. Recurrence of uveitis was significantly associated with surgical failure in trabeculectomy group (odds ratio 4.8, P = 0.02) but not in GDI group.Surgical success rate of GDI was not significantly different from trabeculectomy for uveitic glaucoma in this study. Regular monitoring, early and prolonged intensive treatment of ocular inflammation is important for surgical success particularly following trabeculectomy.

Summary Background Concurrent administration of the immune checkpoint inhibitors nivolumab and ipilimumab has shown greater efficacy than either agent alone in patients with advanced melanoma, albeit with more high-grade adverse events. We assessed whether sequential administration of nivolumab followed by ipilimumab, or the reverse sequence, could improve safety without compromising efficacy. Methods We did this randomised, open-label, phase 2 study at nine academic medical centres in the USA. Eligible patients (aged ≥18 years) with unresectable stage III or IV melanoma (treatment-naive or who had progressed after no more than one previous systemic therapy, with an Eastern Cooperative Oncology Group performance status of 0 or 1) were randomly assigned (1:1) to induction with intravenous nivolumab 3 mg/kg every 2 weeks for six doses followed by a planned switch to intravenous ipilimumab 3 mg/kg every 3 weeks for four doses, or the reverse sequence. Randomisation was done by an independent interactive voice response system with a permuted block schedule (block size four) without stratification factors. After induction, both groups received intravenous nivolumab 3 mg/kg every 2 weeks until progression or unacceptable toxicity. The primary endpoint was treatment-related grade 3–5 adverse events until the end of the induction period (week 25), analysed in the as-treated population. Secondary endpoints were the proportion of patients who achieved a response at week 25 and disease progression at weeks 13 and 25. Overall survival was a prespecified exploratory endpoint. This study is registered with ClinicalTrials.gov, number NCT01783938, and is ongoing but no longer enrolling patients. Findings Between April 30, 2013, and July 21, 2014, 140 patients were enrolled and randomly assigned to nivolumab followed by ipilimumab (n=70) or to the reverse sequence of ipilimumab followed by nivolumab (n=70), of whom 68 and 70 patients, respectively, received at least one dose of study drug and were included in the analyses. The frequencies of treatment-related grade 3–5 adverse events up to week 25 were similar in the nivolumab followed by ipilimumab group (34 [50%; 95% CI 37·6–62·4] of 68 patients) and in the ipilimumab followed by nivolumab group (30 [43%; 31·1–55·3] of 70 patients). The most common treatment-related grade 3–4 adverse events during the whole study period were colitis (ten [15%]) in the nivolumab followed by ipilimumab group vs 14 [20%] in the reverse sequence group), increased lipase (ten [15%] vs 12 [17%]), and diarrhoea (eight [12%] vs five [7%]). No treatment-related deaths occurred. The proportion of patients with a response at week 25 was higher with nivolumab followed by ipilimumab than with the reverse sequence (28 [41%; 95% CI 29·4–53·8] vs 14 [20%; 11·4–31·3]). Progression was reported in 26 (38%; 95% CI 26·7–50·8) patients in the nivolumab followed by ipilimumab group and 43 (61%; 49·0–72·8) patients in the reverse sequence group at week 13 and in 26 (38%; 26·7–50·8) and 42 (60%; 47·6–71·5) patients at week 25, respectively. After a median follow-up of 19·8 months (IQR 12·8–25·7), median overall survival was not reached in the nivolumab followed by ipilimumab group (95% CI 23·7–not reached), whereas over a median follow-up of 14·7 months (IQR 5·6–23·9) in the ipilimumab followed by nivolumab group, median overall survival was 16·9 months (95% CI 9·2–26·5; HR 0·48 [95% CI 0·29–0·80]). A higher proportion of patients in the nivolumab followed by ipilimumab group achieved 12-month overall survival than in the ipilimumab followed by nivolumab group (76%; 95% CI 64–85 vs 54%; 42–65). Interpretation Nivolumab followed by ipilimumab appears to be a more clinically beneficial option compared with the reverse sequence, albeit with a higher frequency of adverse events. Funding Bristol-Myers Squibb.

© 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland

Background: Development of a standardized internet-based system to self-assess skills in optic disc examination for glaucoma risk assessment. Design: Prospective internet-based observational study. Participants: Total of 197 participants (glaucoma subspecialists, general ophthalmologists and trainees) from 22 countries. Methods: Forty-two optic disc images demonstrating a range of features were selected from 2500 monoscopic disc photographs of normal and glaucomatous eyes. Images were presented to clinicians via website (http://www.gone-project.com). Participants were asked to assess nine topographic features and make a subjective assessment of glaucoma likelihood. Main Outcome Measures: Inter-observer agreement using kappa (κ) or weighted kappa (κw). Results: There was substantial level of inter-observer agreement between glaucoma subspecialists for assessment of glaucoma likelihood (κw = 0.63). Inter-observer agreement was high for haemorrhage (κ = 0.83) and substantial for disc size, disc shape, cup:disc ratio, peripapillary atrophy and cup shape (κw = 0.59–0.68). Subspecialists had stronger inter-observer agreement for glaucoma likelihood and for most disc characteristics than did trainees: the greatest difference being the assessment for retinal nerve fibre layer loss. Analysis of individual disc answers from ophthalmology trainees showed that discs leading to lower agreement of glaucoma likelihood tend to produce lower agreement for the assessment of cup:disc ratio, cup shape, cup depth and retinal nerve fibre layer. Discs with features of moderate to deep cup or cup:disc ratio between 0.6 and 0.8 also lead to lower agreement in glaucoma likelihood. Conclusions: This internet-based system is a readily accessible and standardized tool, for clinicians globally, that permits self-assessment and benchmarking of skills in optic disc examination.

TPS3126Background: Although multiple new agents have been approved for mCRPC over the last decade, median survival remains unsatisfactory at ~12-35 months. Immunotherapy targeted solely at programm...

Purpose We hypothesize that: (1) Anterior chamber depth (ACD) is correlated with the relative anteroposterior position of the pupillary image, as viewed from the temporal side. (2) Such a correlation may be used as a simple quantitative tool for estimation of ACD. Methods Two hundred sixty-six phakic eyes had lateral digital photographs taken from the temporal side, perpendicular to the visual axis, and underwent optical biometry (Nidek AL scanner). The relative anteroposterior position of the pupillary image was expressed using the ratio between: (1) lateral photographic temporal limbus to pupil distance (“E”) and (2) lateral photographic temporal limbus to cornea distance (“Z”). In the first chronological half of patients (Correlation Series), E:Z ratio (EZR) was correlated with optical biometric ACD. The correlation equation was then used to predict ACD in the second half of patients (Prediction Series) and compared to their biometric ACD for agreement analysis. Results A strong linear correlation was found between EZR and ACD, R = −0.91, R2 = 0.81. Bland-Altman analysis showed good agreement between predicted ACD using this method and the optical biometric ACD. The mean error was −0.013 mm (range −0.377 to 0.336 mm), standard deviation 0.166 mm. The 95% limits of agreement were ±0.33 mm. Conclusions Lateral digital photography and EZR calculation is a novel method to quantitatively estimate ACD, requiring minimal equipment and training. Translational Relevance EZ ratio may be employed in screening for angle closure glaucoma. It may also be helpful in outpatient medical clinic settings, where doctors need to judge the safety of topical or systemic pupil-dilating medications versus their risk of triggering acute angle closure glaucoma. Similarly, non ophthalmologists may use it to estimate the likelihood of acute angle closure glaucoma in emergency presentations.

PURPOSE: To describe a tangent perimeter developed on an Apple iPad (Melbourne Rapid Field, MRF). METHODS: The MRF assays 66 locations over 28° × 18° by having the patient vary fixation. Spot size and background luminance are paired to yield constant thresholds across the field. Spot locations were selected after analysis of 360 patient records. The capacity of the MRF to detect defects was verified in five participants (age 22-28 years) by simulating four common losses: central, arcuate, quadrant, and hemianopia. We also consider the effect of: myosis, blur (+3 DS), viewing distance (25-75 cm), ambient light (4-600 lux), and retest repeatability (1-week apart) on thresholds. Group means [SEM] are compared by Student's t-test and repeatability returned from Bland-Altman analysis. RESULTS: We found a 5 cd.m-2 background replicates the Weber fraction produced by a Humphrey spot shown at 35 dB. Our variable size gives constant thresholds (29.6 [0.2] dB) across all locations. Altering viewing distance (25 cm = 29.8 [0.9] dB; 75 cm = 28.9 [0.6] dB) and ambient lighting (4 lux, 29.8 [0.8] dB; 600 lux, 29.5 [1.0] dB) did not affect threshold although screen reflections must be avoided. Myosis (-1.2 dB) and blur (-1.5 dB) will reduce sensitivity (P < 0.05). Simulated defects with a mean defect (MD) of -3.3 dB are detected by the MRF. The Coefficient of repeatability was 9.6% (SD ∼2.9 dB) in normal regions and 48.1% (SD ∼8.0 dB) in areas of simulated scotoma. CONCLUSIONS: Tablet technology can return efficient and reliable thresholds to 30° as a tangent perimeter. TRANSLATIONAL RELEVANCE: The MRF will allow testing at a bedside, at home, in rural or remote areas, or where equipment cannot be financed.

Background: Extensive use of polyethylene glycol (PEG) in consumer products necessitates the assessment of anti-PEG antibodies (APAb). Methods: In clinical trials comparing PEG-IFN-λ to PEG-IFN-α, conventional bridge and direct assays were assessed. Results & Conclusion: The bridge assay detected IgM and IgG APAb reactive with common PEG sizes and derivatives at sufficient sensitivity, 15–500 ng/ml. Of subjects evaluated, 6% of PEG-IFN-λ and 9% of PEG-IFN-α subjects had persistent APAb while 60% of PEG-IFN-λ and 33% of PEG-IFN-α subjects had persistent anti-interferon antibodies (AIAb). Pre-existing APAb and AIAb prevalence was comparable (approximately 10% of subjects). APAb were earlier onset, less frequent, less persistent and lower titer than AIAb. No associated hypersensitivity events were reported.

We describe a model of acute intraocular pressure (IOP) elevation in the mouse eye that induces reversible loss of inner retinal function associated with oxidative stress, glial cell activation and minimal loss of retinal ganglion cell (RGC) number. Young healthy mouse eyes recover inner retinal function within 7-days but more persistent functional loss is seen in older mice. Manipulation of diet and exercise further modify RGC recovery demonstrating the utility of this injury model for investigating lifestyle and therapeutic interventions. We believe that systematic investigation into the characteristics and determinants of RGC recovery following an IOP challenge will shed light on processes that govern RGC vulnerability in the early stages of glaucoma.

To determine whether monoscopic vs stereoscopic viewing impacts evaluation of optic disc photographs for glaucoma diagnosis in an expert population.Prospective observational study.Twenty pairs of high-quality monoscopic and stereoscopic photographs of similar size and magnification (ie, 40 images), were selected to demonstrate a range of optic disc features from a total of 197 eyes of 197 patients with glaucoma and normal subjects recruited from a tertiary clinic. These were presented in randomized order via an interactive platform (http://stereo.gone-project.com/). Participants assessed 9 topographic features and estimated glaucoma likelihood for each photograph. Main outcome measures were intra- and inter-observer agreement.There was good intra-observer agreement between monoscopic and stereoscopic assessments of glaucoma likelihood (κw = 0.56). There was also good to substantial agreement for peripapillary atrophy (κw = 0.65), cup shape (κw = 0.65), retinal nerve fiber layer loss (κw = 0.69), vertical cup-to-disc ratio (κw = 0.58), and disc shape (κw = 0.57). However, intra-observer agreement was only fair to moderate for disc tilt, cup depth, and disc size (κw = 0.46-0.49). Inter-observer agreement for glaucoma likelihood in monoscopic photographs (κw = 0.61, 95% confidence interval [CI] = 0.55-0.67) was substantial and not lower than in stereoscopic photographs (κw = 0.59, CI = 0.54-0.65). Monoscopic photographs did not lead to lower levels of inter-observer agreement compared to stereoscopic photographs in the assessment of any optic disc characteristics, for example disc size (mono κw = 0.65, stereo κw = 0.52) and cup-to-disc ratio (mono κw = 0.72, stereo κw = 0.62).For expert observers in the evaluation of optic disc photographs for glaucoma likelihood, monoscopic optic disc photographs did not appear to represent a significant disadvantage compared to stereoscopic photographs.

PURPOSE: To determine the correlation between the perimetric outcomes from perimetry software Melbourne Rapid Fields (MRF) run on an Apple iPad tablet and those from the Humphrey Field Analyzer (HFA). METHODS: The MRF software was designed with features including variable fixation and fast thresholding using Bayes logic. Here, we report a cross-sectional study on 90 eyes from 90 participants: 12 had normal optic nerves and 78 had glaucoma with various degrees of visual field loss (41 mild and 37 moderate-severe). Exclusion criteria were patients with worse than 20/40 vision or recent intraocular surgery. The visual field outcomes of MRF were compared against those returned from the HFA 24-2 SITA standard. Participants were tested twice on the MRF to establish test-retest repeatability. RESULTS: The test durations were shorter on MRF than HFA (5.7 ± 0.1 vs. 6.3 ± 0.1 minutes, P < 0.001). MRF showed a high level of concordance in its outcomes with HFA (intraclass coefficient [ICC] = 0.93 for mean defect [MD] and 0.86 for pattern deviation [PD]) although the MRF tended to give a less negative MD (1.4 dB bias) compared with the HFA. MRF also showed levels of test-retest reliability comparable to HFA (ICC = 0.93 for MD and 0.89 for PD, 95% limits of agreement -4.5 to 4.3 dB). CONCLUSION: The perimetry results from the MRF have a strong correlation to the HFA outcomes. MRF also has test-retest reliability comparable to HFA. TRANSLATIONAL RELEVANCE: Portable tablet perimetry may allow accurate assessment of visual field when standard perimetry machines are unavailable or unsuitable.

Purpose Following the recent demonstration of increased mitochondrial DNA mutations in lymphocytes of POAG patients, the authors sought to characterize mitochondrial function in a separate cohort of POAG. Methods Using similar methodology to that previous applied to Leber's hereditary optic neuropathy (LHON) patients, maximal adenosine triphosphate (ATP) synthesis and cellular respiration rates, as well as cell growth rates in glucose and galactose media, were assessed in transformed lymphocytes from POAG patients (n = 15) and a group of age- and sex-matched controls (n = 15). Results POAG lymphoblasts had significantly lower rates of complex-I-driven ATP synthesis, with preserved complex-II-driven ATP synthesis. Complex-I driven maximal respiration was also significantly decreased in patient cells. Growth in galactose media, where cells are forced to rely on mitochondrial ATP production, revealed no significant differences between the control and POAG cohort. Conclusions POAG lymphoblasts in the study cohort exhibited a defect in complex-I of the oxidative phosphorylation pathway, leading to decreased rates of respiration and ATP production. Studies in LHON and other diseases have established that lymphocyte oxidative phosphorylation measurement is a reliable indicator of systemic dysfunction of this pathway. While these defects did not impact lymphoblast growth when the cells were forced to rely on oxidative ATP supply, the authors suggest that in the presence of a multitude of cellular stressors as seen in the early stages of POAG, these defects may lead to a bioenergetic crisis in retinal ganglion cells and an increased susceptibility to cell death.

Advancing age is a major risk factor for many neurodegenerative diseases but the underlying pathophysiology is not clear. We hypothesize that aging impairs the ability of neurons in the central nervous system to recover functionally after injury. To test this in retinal ganglion cells in vivo, we developed an optic nerve “stress test” which monitors the functional capacity of the optic nerve and retina, during and after a subischemic injury induced by intraocular pressure elevation. We report that older (18-month) C57BL/6J mice suffered greater loss of inner retinal function compared with younger adult mice following intraocular pressure (IOP) challenge. To investigate whether age-related vulnerability to IOP challenge can be modified, we subjected 12-month-old mice to dietary restriction (DR) (alternate-day fasting) for 6 months. Compared with age-matched ad libitum fed controls, DR mice showed greater recovery in inner retinal function following IOP challenge. DR was associated with reduced oxidative stress level following injury and improved mitochondrial oxidative phosphorylation enzyme activity compared with ad libitum controls. Taken together, this study provides in vivo evidence that DR improves functional recovery of the retina following injury and points to the potential benefits of therapies that target mitochondria for the protection of the aging retina and optic nerve against injury.

The increasing demand for higher power density and lower cost in high voltage power supplies has driven semiconductor manufacturers to expand IGBT performance for high switching frequency beyond 100 kHz. An ultra thin punch-through IGBT with a blocking voltage of 650V has been developed and optimized targeting DC-DC conversion up to 200 kHz. Its high Tjmax of 175°C further enhances the converter compactness. This paper describes the feature of this ultra fast IGBT in a critical comparison with equivalent products available on the market today.

Large IGBTs with a current rating of 300A and a blocking voltage of 650V on ultra thin wafers have been successfully developed with double-sided cooling capability. The deposition of solderable metals on the front and back sides of the IGBT produced flat thin wafers with less than 2 mm warpage and good mechanical yield. A large reduction of on-state voltage drop 390 mV at 300A is achieved in a wirebond-less Cu-clip package. The combination of lower on-state voltage drop and larger heat exchange area increases the IGBT current carrying capability by 200%.