SF-6D utility values for the better- and worse-seeing eye for health states based on the Snellen equivalent in patients with age-related macular degeneration

Objective: Economic evaluations in wet age-related macular degeneration (ARMD) is hampered as often utility values for solely one eye are used, mostly the better-seeing eye (BSE). Moreover, frequently chosen methods rely on patient values and/or disease specific measures, while economic evaluations prefer generic quality of life (QoL) measures based on societal preferences. The generic QoL utility instrument EQ-5D has shown to be insensitive for differences in visual acuity. The aim of this study was therefore to provide societal utility values, using the generic SF-6D, for health states acknowledging both BSE and worse-seeing eye (WSE). Methods: SF-6D utility values of 191 ARMD patients (≤65 years) with 153 follow-up measures at 1 year were used to fill health states defined by the combination of BSE and WSE using Snellen equivalents; no visual loss (≥20/40), mild-moderate (20/200) and severe (≤20/200). Results: QoL utilities were estimated for the SF-6D, ranging from 0.740 for ARMD patients without visual loss to 0.684 for patients with a combination of mild-moderate visual loss in their BSE and severe visual loss in their WSE. Conclusion: Societal utility values are provided for ARMD patients using the generic QoL instrument SF-6D for visual acuity health states based on both BSE and WSE. The range of the values is smaller than previous elicited utilities with the disease-specific VisQoL. Besides, the utility values are placed on a more realistic position on the utility scale, and SF-6D utility values avoid the problem associated with the interpretation of disease-specific utility values

Outcomes in patients with chronic uveitis: which factors matter to patients? A qualitative study

PURPOSE: Outcome measurements currently used in chronic uveitis care fail to cover the full patient perspective. The aim of this study is to develop a conceptual model of the factors that adult patients with chronic uveitis consider to be important when evaluating the impact of their disease and treatment. METHODS: A qualitative study design was used. Twenty chronic uveitis patients were recruited to participate in two focus groups. Data were transcribed verbatim and analysed using thematic analysis in ATLAS.ti. RESULTS: Coding of the transcripts resulted in a total of 19 codes divided over five themes: 1) disease symptoms and treatment; 2) diagnosis and treatment process; 3) impact on daily functioning; 4) emotional impact; and 5) treatment success factors. CONCLUSION: The conceptual model resulting from this study can contribute to the development of future uveitis specific measures in adults

Six and eight weeks injection frequencies of bevacizumab are non-inferior to the current four weeks injection frequency for quality of life in neovascular age-related macular degeneration: a randomized controlled trial

Purpose: Patients with neovascular age-related macular degeneration (nARMD) will not deteriorate on visual acuity and retinal thickness when treated with bevacizumab injection frequencies of 6 or 8 weeks compared to 4 weeks. This study aimed to investigate this non-inferiority in quality of life (QoL). We hypothesized that less frequent bevacizumab injections are not inferior regarding patients reported QoL. Methods: Patients were randomized to bevacizumab every 4 (n = 64), 6 (n = 63), and 8 weeks (n = 64). Patients were at least 65 years old, have a best-corrected visual acuity of 20/200 to 20/20, no previous ARMD treatment and active leakage. Vision-related QoL questionnaire NEI VFQ-39 was used to assess QoL at baseline and after 1 year. General QoL questionnaire SF-36 was included for secondary analysis. Multilevel analyses were performed, correcting for age, gender and baseline. Results: The 6 (3.68; 95% CI − 0.63 to 8.00) and 8 (2.15; 95% CI − 2.26 to 6.56) weeks bevacizumab regimens resulted in non-inferior QoL differences compared to 4 weeks on the NEI VFQ-39. Also on the SF-36 the differences were well within the non-inferiority limits. Conclusion: Non-inferiority of the 6 and 8 weeks frequencies was demonstrated compared to 4 weeks on vision-related and general QoL in patients with nARMD. These results are in line with previously published results of lower frequency injections regarding visual acuity and central retinal thickness. Lower injection frequency may reduce burden, side effects, and treatment costs. In consideration of these results, 8 weeks frequency injections of intravitreal bevacizumab could be considered in patients with nARMD

Are Patients at Risk for Recurrent Disease Activity After Switching From Remicade® to Remsima®? An Observational Study

Background: Since the late ‘90s, infliximab (Remicade®) is being used successfully to treat patients with several non-infectious immune mediated inflammatory diseases (IMIDs). In recent years, infliximab biosimilars, including Remsima® were introduced in clinical practice. Aim: To investigate the interchangeability of Remicade® (originator infliximab) and its biosimilar Remsima® in patients with rare immune-mediated inflammatory diseases (IMIDs). Methods: This two-phased prospective open label observational study was designed to monitor the transition from Remicade® to Remsima® in patients with rare IMIDs. All included patients were followed during the first 2 years. The primary endpoint was the demonstration of non-difference in quality of life and therapeutic efficacy, as measured by parameters including a safety monitoring program, physicians perception of disease activity (PPDA) and patient self-reported outcomes (PSROs). Secondary outcomes included routine blood analysis, pre-infusion serum drug concentration values and anti-drug antibody formation. Results: Forty eight patients treated with Remicade® were switched to Remsima® in June-July 2016 and subsequently monitored during the first 2 years. The group consisted of patients with sarcoidosis (n = 17), Behçet's disease (n = 12), non-infectious uveitis (n = 11), and other diagnoses (n = 8). There were no significant differences in PPDA, PSROs, clinical and laboratory assessments and pre-infusion serum drug concentrations between the groups. De novo anti-drug antibodies were observed in two patients. Seven patients with sarcoidosis and five with another diagnosis developed a significant disease relapse (n = 7) or adverse events (n = 5) within 2 years; 10 of these patients discontinued Remsima® treatment, one withdrew from the study and one received additional corticosteroid therapy. Conclusions: We observed no significant differences in PSROs, PPDA and laboratory parameters after treatment was switched from Remicade® to Remsima®. However, disease relapse or serious events were observed in 12 out of 48 patients when treatment was switched from Remicade® to Remsima®. The choice to switch anti-TNF alpha biologics in patients with rare IMIDs, particularly in sarcoidosis, requires well-considered decision-making and accurate monitoring due to a possibly higher incidence of disease worsening

Treatment strategies in primary vitreoretinal lymphoma: a 17-center European collaborative study.

IMPORTANCE: The best treatment option for primary vitreoretinal lymphoma (PVRL) without signs of central nervous system lymphoma (CNSL) involvement determined on magnetic resonance imaging or in cerebrospinal fluid is unknown. OBJECTIVE: To evaluate the outcomes of treatment regimens used for PVRL in the prevention of subsequent CNSL. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted at 17 referral ophthalmologic centers in Europe. We reviewed clinical, laboratory, and imaging data on 78 patients with PVRL who did not have CNSL on presentation between January 1, 1991, and December 31, 2012, with a focus on the incidence of CNS manifestations during the follow-up period. INTERVENTIONS: The term extensive treatment was used for various combinations of systemic and intrathecal chemotherapy, whole-brain radiotherapy, and peripheral blood stem cell transplantation. Therapy to prevent CNSL included ocular radiotherapy and/or ocular chemotherapy (group A, 31 patients), extensive systemic treatment (group B, 21 patients), and a combination of ocular and extensive treatment (group C, 23 patients); 3 patients did not receive treatment. A total of 40 patients received systemic chemotherapy. MAIN OUTCOMES AND MEASURES: Development of CNSL following the diagnosis of PVRL relative to the use or nonuse of systemic chemotherapy and other treatment regimens. RESULTS: Overall, CNSL developed in 28 of 78 patients (36%) at a median follow-up of 49 months. Specifically, CNSL developed in 10 of 31 (32%) in group A, 9 of 21 (43%) in group B, and 9 of 23 (39%) in group C. The 5-year cumulative survival rate was lower in patients with CNSL (35% [95% CI, 50% to 86%]) than in patients without CNSL (68% [95% CI, 19% to 51%]; P = .003) and was similar among all treatment groups (P = .10). Adverse systemic effects occurred in 9 of 40 (23%) patients receiving systemic chemotherapy; the most common of these effects was acute renal failure. CONCLUSIONS AND RELEVANCE: In the present series of patients with isolated PVRL, the use of systemic chemotherapy was not proven to prevent CNSL and was associated with more severe adverse effects compared with local treatment

The Nucleocapsid Region of HIV-1 Gag Cooperates with the PTAP and LYPXnL Late Domains to Recruit the Cellular Machinery Necessary for Viral Budding

HIV-1 release is mediated through two motifs in the p6 region of Gag, PTAP and LYPXnL, which recruit cellular proteins Tsg101 and Alix, respectively. The Nucleocapsid region of Gag (NC), which binds the Bro1 domain of Alix, also plays an important role in HIV-1 release, but the underlying mechanism remains unclear. Here we show that the first 202 residues of the Bro1 domain (Broi) are sufficient to bind Gag. Broi interferes with HIV-1 release in an NC–dependent manner and arrests viral budding at the plasma membrane. Similar interrupted budding structures are seen following over-expression of a fragment containing Bro1 with the adjacent V domain (Bro1-V). Although only Bro1-V contains binding determinants for CHMP4, both Broi and Bro1-V inhibited release via both the PTAP/Tsg101 and the LYPXnL/Alix pathways, suggesting that they interfere with a key step in HIV-1 release. Remarkably, we found that over-expression of Bro1 rescued the release of HIV-1 lacking both L domains. This rescue required the N-terminal region of the NC domain in Gag and the CHMP4 binding site in Bro1. Interestingly, release defects due to mutations in NC that prevented Bro1 mediated rescue of virus egress were rescued by providing a link to the ESCRT machinery via Nedd4.2s over-expression. Our data support a model in which NC cooperates with PTAP in the recruitment of cellular proteins necessary for its L domain activity and binds the Bro1–CHMP4 complex required for LYPXnL–mediated budding

Endophthalmitis after strabismus surgery: incidence and outcome in relation to age, operated eye muscle, surgical technique, scleral perforation and immune state

Purpose: Identify risk factors for endophthalmitis after strabismus surgery (EASS) and relate these to incidence and outcome. Methods: Ophthalmologists, who had operated, diagnosed or treated EASS, completed a case record form with 71 questions in six domains: Preoperative, Surgery, Perforation, Postoperative, Outcome and Experts’ opinion. To estimate the age-specific incidence per number of strabismus operations in the Netherlands during 1994-2013, the age distribution of Dutch cases was compared with the age-specific rates of strabismus surgery in the Dutch Registry of Strabismus Operations and with population data. Exploratory data analysis was performed. The immune state was evaluated in six patients. Five enucleated eyes were studied histopathologically. Results: None of the 26 patients (27 eyes with EASS) were between 9 and 65 years old, except for one patient with retinal haemorrhage followed by endophthalmitis. In the Netherlands during 1994-2013, the rate of EASS was approximately one per 11 000 strabismus operations, but one per 4300 for children aged 0–3 and one per 1000 for patients 65 and older. Endophthalmitis was diagnosed on postoperative day 1–4 in children aged 0–3. In all 15 children aged 0–5, the 16 affected eyes were phthisical, eviscerated or enucleated. The involved eye muscle had been recessed in 25 of 27 cases. It was a medial rectus in 15 of 16 children aged 0–6. It was a lateral (6), inferior (2) or medial (1) rectus in elderly. Scleral perforation went unnoticed in all children (no record in three) and in two of seven elderly (no record in two). Histopathology showed transscleral scarring compatible with scleral perforation in four patients but, in a two-year-old girl who had EASS together with a transient medial rectus palsy, the sclera underneath the former suture tract was not perforated but did contain the long posterior ciliary artery. Conclusions: Endophthalmitis after strabismus surgery (EASS) affects children and elderly, with a grave outcome in young children. It occurs after recession of the medial rectus muscle in children, and it may occur without scleral perforation. Age and perforation influence many other parameters that determine the occurrence and fulminance of EASS