Abstract Background Therapeutic drug monitoring (TDM) helps guide use of anti-TNF drugs in IBD patients. In addition, higher anti-TNF levels during induction therapy have been shown to be associated with better clinical and endoscopic outcomes. The role of TDM for more novel biologics such as ustekinumab (an anti- IL-12/23 antibody used to treat Crohn’s disease) remains to be elucidated. Aims We set out to investigate correlations between ustekinumab drug levels measured during induction with clinical and biochemical outcomes in patients with Crohn’s disease. Methods Patients with Crohn’s disease commencing treatment with ustekinumab were recruited from a single tertiary referral centre. Standard weight-based induction dosing was used. TDM was performed at week 2 and week 6 following IV induction dose. A drug-tolerant assay (Prometheus) was used. Kruskal-Wallis test was used to examine association between induction dose and ustekinumab levels. CDAI, CRP, and faecal calprotectin (FCP) were measured at week 12. Pearson correlation co-efficient was used to assess the relationship between ustekinumab levels and i)CDAI ii)CRP and iii)FCP at week 12. Results A total of 38 ustekinumab levels in 21 patients were measured. Week 2 ustekinumab levels were available for 17 patients, 16 (94.1%) of whom had levels of greater or equal to 25μg/mL. (1 patient had a level of 19.5μg/mL.) Week 6 ustekinumab levels were available for 21 patients; median 15μg/mL (IQR 9.9–21.3). No patients had detectable antibodies to ustekinumab. There was no significant association between absolute induction dose and week 6 ustekinumab levels; p=0.46. Of the 21 patients with week 6 levels, CDAI, CRP and FCP were available for 18, 18 and 16 patients respectively; Median CDAI 103(IQR 42–249), median CRP 2.3mg/L(IQR 1.0–11.3), median FCP 269μg/g(IQR109-932). There was a significant negative correlation between week 6 ustekinumab levels and CDAI; r=-.609, p=0.007. A negative correlation between week 6 ustekinumab levels and FCP was also significant; r=-.526, p=0.037. There was no significant correlation between week 6 ustekinumab levels and CRP; r=-.259, p=0.298. Conclusions We have demonstrated inter-patient variation in drug pharmacokinetics at week 6 following induction dose of ustekinumab in patients with Crohn’s disease. Drug levels at week 6 are significantly associated with clinical and biochemical markers of disease activity (CDAI, faecal calprotectin) at week 12. Measurement of week 6 ustekinumab levels may aid early identification of patients at risk of primary non-response to ustekinumab. Funding Agencies Testing provided by Prometheus
Purpose: The purpose of this study was to assess the influence of blue light-filtering intraocular lenses (IOL) on peripapillary retinal nerve fiber layer (RNFL) thickness measurements by spectral-domain (SD) optical coherence tomography (OCT).Methods: This prospective study included 50 eyes of 50 patients. Patients were randomly assigned to receive either a blue light-filtering IOL (acrysof IQ (SN60WF) [Alcon]) or a clear IOL (Tecnis (Z9003) [AMO]). The peripapillary RNFL thickness was measured using a Cirrus SD OCT before and 8 weeks after cataract surgery. Perioperative differences in RNFL thickness measurements and signal strengths (SS) were evaluated and compared in both IOL groups.Results: Thirty-nine eyes of 39 patients were included in the final analysis. There was a significant increase in average RNFL thickness and SS after cataract surgery in both IOL groups. No significant difference in perioperative changes of RNFL measurements was noted between yellow and clear IOL groups. In the multivariable analysis, the factor affecting perioperative differences of RNFL measurements was not IOL type but SS.Conclusions: Our data suggests that blue-light filtering IOL does not influence RNFL thickness measurements by Cirrus SD-OCT.
This study assessed the clinical risk factors for periorbital dermatitis (PD) after using dorzolamide/timolol eye drops in a total of 1282 glaucoma patients. Both the PD(+) group and the PD(-) group were evaluated using clinical data such as age, sex, dosing duration, presence of benzalkonium chloride (BAK) in the formulation, ocular surgery history (e.g. cataract or glaucoma operations), height, weight, personal history of systemic hypertension, smoking, alcohol consumption, intraocular pressure, best-corrected visual acuity (BCVA), central corneal thickness, axial length, and visual field index (VFI). Univariate analyses showed that shorter dosing duration, higher rate of BAK-included cases, worse BCVA, worse VFI, more systemic hypertension history, and more ocular surgery history were more associated with the PD(+) group than the PD(-) group. The BAK(-) group showed a lower PD rate than the BAK-included group, which was supported by the Kaplan-Meier analysis (log-rank test, p = 0.0014). Multivariate analyses revealed that the probability of PD increased by 8 times if they had a history of ocular surgery and increased by 2.3% when the VFI decreased by 1% (Cox's hazard regression test, p < 0.001). Therefore, a preservative-free dorzolamide/timolol can benefit the subjects for those who had ocular surgery or who have worse VFI.
To evaluate the therapeutic efficacy, safety and tolerability of newly developed preservative-free (PF) latanoprost generic [TJO-002] and compare it with benzalkonium chloride (BAK)-preserved latanoprost [Xalatan®] in patients with primary open angle glaucoma (POAG) and ocular hypertension (OHT).Included patients were aged ≥19y with POAG/OHT. After a washout period, patients with IOP 21-35 mm Hg at 9 a.m. were enrolled. After a full ophthalmic and glaucoma examination, 144 patients with POAG and OHT participated in this study. Subjects were randomly assigned either PF latanoprost (74 eyes) or BAK-preserved latanoprost (70 eyes). All subjects were examined at 4, 8, and 12wk after first administration. At each follow-up visit, IOP was measured at 9 a.m. and 5 p.m. and compliance was assessed. Throughout the study, all adverse events were recorded and monitored by the masked investigators who measured IOP.Both groups showed a statistically significant decrease of average diurnal IOP at 12wk compared to baseline (-7.21±3.10 mm Hg in the PF latanoprost group and -7.02±3.17 mm Hg in the BAK latanoprost group, both P<0.0001). There was no statistically significant diurnal IOP variation between the groups. In terms of tolerability, pruritus, burning/stinging, and sticky eye sensation, severity was significantly lower in the PF latanoprost group than in the BAK latanoprost group (P<0.05).PF latanoprost has at least similar efficacy in terms of IOP reduction and better tolerability compared with BAK latanoprost.
Purpose: To characterize the clinical and biological properties of biodegradable collagen matrices (BCMs) for possible glaucoma drainage device implantation. Methods: A total of 68 refractory glaucoma eyes, followed up postoperatively for at least 6 months, were consecutively enrolled after retrospective chart review. The BCM-augmented Ahmed valve implantations (BAAVI) using our Ologen-6 and Ologen-7 valves were performed and compared with a conventional method. Complete surgical success was defined as an IOP of ≤21 mm Hg (IOP 1) or ≤17 mm Hg (IOP 2) without antiglaucoma medications. Qualified success was defined as an IOP ≤21 mm Hg with or without antiglaucoma medications. The biological properties of each BCM were assessed by enzymatic degradation rates via collagenase under ocular physiological conditions. Results: The mean ages and preoperative IOPs were similar for the groups. In the conventional, BAAVI with Ologen-6, and BAAVI with Ologen-7 groups, complete success rates with target IOP 1 were 29.2%, 40.0%, and 66.7%; those with target IOP 2 were 12.5%, 30.0%, and 45.8%; qualified success rates were 45.8%, 55.0%, and 75.0%, respectively. The enzymatic degradation rate of Ologen-7 was significantly slower than that of Ologen-6 (12.5 × 10−3 vs. 28.8 × 10−3). Conclusions: The surgical success rate was highest in the Ologen-7 BAAVI group, with the lowest dependency on postoperative antiglaucoma medication use compared with the conventional and Ologen-6 BAAVI groups. The clinical results correlated with the different biological and physicochemical properties based on the degree of enzymatic degradation and on the structural morphology.
Deep sclerectomy (DS), one of the non-penetrating glaucoma surgeries, has been reported to be a safe and effective surgical procedure which provides long-term intraocular pressure (IOP) control in the management of open-angle glaucoma.Several studies comparing surgical outcomes of DS with those of trabeculectomy have also shown that DS provides less but comparable IOP reduction with fewer complications [1,2].However, the surgical outcomes of DS may have racial differences.Although East Asian eyes are reported to ethnically differ in many aspects from other races, there are few reports about the long-term surgical results of DS in Asian populations.This report evaluates the long-term results of DS with small collagen implants in Korean open-angle glaucoma (OAG) patients. Materials and MethodsAfter the approval of the institutional review board, 65 subjects with planned deep sclerectomy with collagen implant (DSCI) with or without the adjunctive use of mitomycin C due to primary and secondary OAG were retrospectively collected.All subjects were Korean (single ethnic group).All surgical procedures were performed by a single surgeon.A one-third scleral thickness, limbal-based, 5.0 mm × 5.0 mm scleral flap was dissected.In the cases using mitomycin C, pieces of surgical sponge soaked with 0.
The progressive and irreversible degeneration of retinal ganglion cells (RGCs) and their axons is the major characteristic of glaucoma, a leading cause of irreversible blindness worldwide. Nicotinamide adenine dinucleotide (NAD) is a cofactor and metabolite of redox reaction critical for neuronal survival. Supplementation with nicotinamide (NAM), a precursor of NAD, can confer neuroprotective effects against glaucomatous damage caused by an age-related decline of NAD or mitochondrial dysfunction, reflecting the high metabolic activity of RGCs. However, oral supplementation of drug is relatively less efficient in terms of transmissibility to RGCs compared to direct delivery methods such as intraocular injection or delivery using subconjunctival depots. Neither method is ideal, given the risks of infection and subconjunctival scarring without novel techniques. By contrast, extracellular vesicles (EVs) have advantages as a drug delivery system with low immunogeneity and tissue interactions. We have evaluated the EV delivery of NAM as an RGC protective agent using a quantitative assessment of dendritic integrity using DiOlistics, which is confirmed to be a more sensitive measure of neuronal health in our mouse glaucoma model than the evaluation of somatic loss via the immunostaining method. NAM or NAM-loaded EVs showed a significant neuroprotective effect in the mouse retinal explant model. Furthermore, NAM-loaded EVs can penetrate the sclera once deployed in the subconjunctival space. These results confirm the feasibility of using subconjunctival injection of EVs to deliver NAM to intraocular targets.
To determine the early predictors of surgical success 6 months after XEN surgery among clinical parameters, including anterior segment optical coherence tomography (AS-OCT).A total of 31 eyes with medically uncontrolled primary open-angle glaucoma or pseudoexfoliation glaucoma was enrolled retrospectively. Using AS-OCT, XEN tip location was categorized into intraconjunctival, intratenon, or uviform at day 1 and blebs were classified into no or low, high sparse, high thick, cystic, or mixed walls at month 6. Using slit-lamp photography, blebs were classified into no or low, localized avascular, diffuse avascular, localized vascular, or diffuse vascular blebs at month 6. Surgical success was defined as an intraocular pressure (IOP) of less than 14 mm Hg.Intraconjunctival and intratenon locations of the tip mostly created a high sparse wall, whereas the uviform type mostly created no or low wall and no or low bleb. The uviform type was linked to pseudoexfoliation glaucoma. A high sparse wall and diffuse avascular bleb showed a lower mean IOP than a high thick wall and localized vascular bleb. In the multivariate analysis, female sex and IOP at week 1 were early predictors of surgical success (8.45 times and 33.1% per 1 mm Hg-decrease, respectively).Bleb evaluation using AS-OCT is valuable to correlate tip location and bleb morphology with clinical profiles, considering that a lower early postoperative IOP is linked to surgical success.Bleb analysis using AS-OCT on day 1 could help to predict bleb morphology after 6 months, which is important to maintain the functioning bleb in the longer term.
'/%3e%3c/defs%3e%3cpath fill='%23012169' d='M0 0h10080v5040H0z'/%3e%3cpath stroke='%23fff' stroke-width='.6' d='m0 0 6 3m0-3L0 3' clip-path='url(%23b)' transform='scale(840)'/%3e%3cpath stroke='%23e4002b' stroke-width='.4' d='m0 0 6 3m0-3L0 3' clip-path='url(%23c)' transform='scale(840)'/%3e%3cpath stroke='%23fff' stroke-width='840' d='M2520 0v2520M0 1260h5040'/%3e%3cpath stroke='%23e4002b' stroke-width='504' d='M2520 0v2520M0 1260h5040'/%3e%3cg fill='%23fff'%3e%3cuse xlink:href='%23d' x='2520' y='3780'/%3e%3cuse xlink:href='%23a' x='7560' y='4200'/%3e%3cuse xlink:href='%23a' x='6300' y='2205'/%3e%3cuse xlink:href='%23a' x='7560' y='840'/%3e%3cuse xlink:href='%23a' x='8680' y='1869'/%3e%3cuse xlink:href='%23e' x='8064' y='2730'/%3e%3c/g%3e%3c/svg%3e)
