IMPORTANCE: For the management of retinal disease, the use of intravitreous injections of anti–vascular endothelial growth factor has increased. Recent reports have suggested that this therapy may ...cause sustained elevation of intraocular pressure (IOP) and may potentially increase the risk of glaucoma for patients with retinal disease. OBJECTIVE: To assess the risk of sustained IOP elevation or the need for IOP-lowering treatments for eyes with diabetic macular edema following repeated intravitreous injections of ranibizumab. DESIGN, SETTING, AND PARTICIPANTS: An exploratory analysis was conducted within a Diabetic Retinopathy Clinical Research Network randomized clinical trial. Study enrollment dates were from March 20, 2007, to December 17, 2008. Of 582 eyes (of 486 participants) with center-involved diabetic macular edema and no preexisting open-angle glaucoma, 260 were randomly assigned to receive a sham injection plus focal/grid laser treatment, and 322 were randomly assigned to receive ranibizumab plus deferred or prompt focal/grid laser treatment. MAIN OUTCOMES AND MEASURES: The cumulative probability of sustained IOP elevation, defined as IOP of at least 22 mm Hg and an increase of at least 6 mm Hg from baseline at 2 consecutive visits, or the initiation or augmentation of ocular hypotensive therapy, through 3 years of follow-up. RESULTS: The mean (SD) baseline IOP in both treatment groups was 16 (3) mm Hg (range, 5-24 mm Hg). The cumulative probability of sustained IOP elevation or of initiation or augmentation of ocular hypotensive therapy by 3 years, after repeated ranibizumab injections, was 9.5% for the participants who received ranibizumab plus prompt or deferred focal/grid laser treatment vs 3.4% for the participants who received a sham injection plus focal/grid laser treatment (difference, 6.1% 99% CI, −0.2% to 12.3%; hazard ratio, 2.9 99% CI, 1.0-7.9; P = .01). The distribution of IOP and the change in IOP from baseline at each visit through 3 years were similar in each group. CONCLUSIONS AND RELEVANCE: In eyes with center-involved diabetic macular edema and no prior open-angle glaucoma, repeated intravitreous injections of ranibizumab may increase the risk of sustained IOP elevation or the need for ocular hypotensive treatment. Clinicians should be aware of this risk and should consider this information when following up with patients who have received intravitreous injections of anti–vascular endothelial growth factor for the treatment of diabetic macular edema.
To compare blood pressure and urine albumin-creatinine ratio over time for participants receiving aflibercept, bevacizumab, or ranibizumab.
Preplanned secondary analyses from a randomized trial ...comparing aflibercept, bevacizumab, and ranibizumab for diabetic macular edema (DME). The Diabetic Retinopathy Clinical Research Network (DRCR.net) enrolled 660 participants with DME and visual acuity 20/32 or worse in at least one eye. Eyes received intravitreous injections of 2.0 mg aflibercept, 1.25 mg bevacizumab, or 0.3 mg ranibizumab based on a structured retreatment protocol over 2 years. Main outcome measures were (1) a change in blood pressure at 2 years, and (2) a change in urine albumin-creatinine ratio (UACR) at 1 year.
At baseline, 95 participants (14%) had normal blood pressure, 220 (33%) had borderline blood pressure elevation, 206 (31%) had mild blood pressure elevation, and 139 (21%) had moderate blood pressure elevation. Average change in mean arterial pressure from baseline to 2 years was -1.2 ± 15, -1.8 ± 13.5, -2.6 ± 14.4 mm Hg in the aflibercept, bevacizumab, and ranibizumab groups, respectively (global P = 0.69). At baseline 247 participants (38%) had no albuminuria (<30 mg/g), 195 (30%) had microalbuminuria (30-300 mg/g), and 212 (32%) had macroalbuminuria (>300 mg/g). Changes in UACR category were not different among treatment groups at the 52-week visit (global P = 0.29).
There do not appear to be treatment group differences for changes in blood pressure or UACR as a reflection of kidney function in patients with DME treated with aflibercept, bevacizumab, or ranibizumab.
The purpose of this study was to determine whether the risk of dislocation and/or revision following THA is increased in patients with a history of prior lumbar fusion given the alterations in ...dynamic pelvic motion following LSF.
A total of 62,387 patients (5% Medicare part B claims database) were identified from 1997 to 2014 with primary THA. From this group, 1809 patients (2.9%) were stratified to identify those with prior lumbar fusion within 5 years of primary THA to compare risk of dislocation and revision with those without lumbar fusion. Multivariate cox regression analysis was performed adjusting for age, socioeconomic status, race, census, region, gender, Charlson score, preexisting conditions, and type of fusion.
Between years 2002 and 2014, there was a 293% increase in the number of patients with prior lumbar fusion undergoing THA. Prevalence of hip dislocation in patients with lumbar fusion before THA was 7.4% compared to 4.8% without fusion, P < .001. There was an 80% increase in dislocation in the fusion group at 6 months, 71% at 1 year, and 60% at 2 years. There was a 48% increased risk of failure leading to revision hip surgery in patients with fusion at 6 months, 41% at 1 year, and 47% at 2 years. Dislocation was the most common mode of failure leading to revision in both the fusion group (20.8%) and the nonfusion group (16%).
Results of this study demonstrate that lumbar fusion before THA is an independent risk factor for dislocation leading to increased risk of revision THA.
IMPORTANCE: The Diabetic Retinopathy Clinical Research Network Protocol S randomized clinical trial results suggest that ranibizumab is a reasonable treatment alternative to panretinal ...photocoagulation (PRP) when managing proliferative diabetic retinopathy (PDR), with or without concomitant baseline diabetic macular edema (DME). However, ranibizumab injections are costly. Thus, it would be useful to examine the relative cost-effectiveness of these 2 treatment modalities. OBJECTIVE: To evaluate incremental cost-effectiveness ratios of 0.5-mg ranibizumab therapy vs PRP for PDR. DESIGN, SETTING, AND PARTICIPANTS: Preplanned secondary analysis using efficacy, safety, and resource utilization data through 2 years of follow-up at 55 US sites for 213 adults with PDR. Data were collected from February 2012 to January 2015. INTERVENTIONS: Intravitreous 0.5-mg ranibizumab at baseline and as frequently as every 4 weeks based on a structured retreatment protocol or PRP at baseline for PDR. Eyes in both groups could receive ranibizumab for concomitant DME. MAIN OUTCOMES AND MEASURES: Incremental cost-effectiveness ratios of ranibizumab compared with PRP evaluated within 2 prespecified subgroups for the study eye: with baseline vision-impairing (Snellen equivalent 20/32 or worse) DME and without baseline vision-impairing DME. RESULTS: The study included 305 adults with PDR, the mean age was 52 years, 44% were women, and 52% were white. Of the 46 participants with PDR and vision-impairing DME at baseline, 21 were assigned to the ranibizumab group and 25 to the PRP group (plus ranibizumab for DME). Among the remaining participants without baseline vision-impairing DME, 80 and 87 were in the ranibizumab and PRP groups, respectively. For participants with and without baseline vision-impairing DME, the incremental cost-effectiveness ratios of ranibizumab therapy compared with PRP were $55 568/quality-adjusted life-year and $662 978/quality-adjusted life-year, respectively, over 2 years. CONCLUSIONS AND RELEVANCE: Over 2 years, compared with PRP, 0.5-mg ranibizumab as given in this trial is within the $50 000/quality-adjusted life-year to $150 000/quality-adjusted life-year range frequently cited as cost-effective in the United States for eyes presenting with PDR and vision-impairing DME, but not for those with PDR without vision-impairing DME. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01489189.
Some insurance companies mandate a form of step therapy, which involves initial use of an inexpensive drug, bevacizumab, to treat diabetic macular edema. This trial compared two treatments: step ...therapy and use of a more expensive drug.
Abstract Purpose Compare patient-centered outcomes in patients with proliferative diabetic retinopathy (PDR) treated with ranibizumab versus panretinal photocoagulation (PRP). Design Randomized ...clinical trial. Methods Setting : Multicenter (55 US sites). Patient Population : 216 adults with one study eye out of 305 adults (excluding participants with two study eyes since each eye received a different treatment) with PDR, visual acuity 20/320 or better, no history of PRP. Intervention : Ranibizumab (0.5-mg/0.05mL) versus PRP. Main Outcome Measures : Change from baseline to 2 years in composite and pre-specified subscale scores from the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25), University of Alabama Low Luminance Questionnaire (UAB-LLQ), Work Productivity and Activity Impairment Questionnaire (WPAIQ). Results For the NEI VFQ-25 and UAB-LLQ composite scores, ranibizumab-PRP treatment group differences (95% CI) were +4.0 (-0.2, +8.3, P =0.06) and +1.8 (-3.5, +7.1, P =0.51) at 1 year, and +2.9 (-1.5, +7.2, P =0.20) and +2.3 (-2.9, +7.5, P =0.37) at 2 years, respectively. Work productivity loss measured with the WPAIQ was 15.6% less with ranibizumab (-26.3%, -4.8%, P =0.005) at 1 year and 2.9% (-12.2%, +6.4%, P =0.54) at 2 years. Eighty-three ranibizumab participants (97%) were 20/40 or better in at least one eye (visual acuity requirement to qualify for an unrestricted driver license in many states) at 2 years compared with 82 PRP participants (87%, adjusted risk ratio=1.1, 95% CI: 1.0, 1.2 P =0.005). Conclusions While differences in some work productivity and driving-related outcomes favored ranibizumab over PRP, no differences between treatment regimens for PDR were identified for most of the other patient-centered outcomes considered.
Assess associations of 2-year visual acuity (VA) outcomes with VA and optical coherence tomography central subfield thickness (CST) after 12 weeks of anti–vascular endothelial growth factor treatment ...for diabetic macular edema in DRCR.net Protocol T.
Randomized clinical trial.
Setting: Multicenter (89 U.S. sites). Patient Population: Eyes with VA and CST data from baseline and 12-week visits (616 of 660 eyes randomized 93.3%). Intervention: Six monthly injections of 2.0 mg aflibercept, 1.25 mg bevacizumab, or 0.3 mg ranibizumab; subsequent injections and focal/grid laser as needed for stability. Main Outcome Measures: Change in VA from baseline and VA letter score at 2 years.
Twelve-week VA response was associated with 2-year change in VA and 2-year VA letter score for each drug (P < .001) but with substantial individual variability (multivariable R2 = 0.38, 0.29, and 0.26 for 2-year change with aflibercept, bevacizumab, and ranibizumab, respectively). Among eyes with less than 5-letter gain at 12 weeks, the percentages of eyes gaining 10 or more letters from baseline at 2 years were 42% (20 of 48), 31% (21 of 68), and 47% (28 of 59), and median 2-year VA was 20/32, 20/32, and 20/25, in the aflibercept, bevacizumab, and ranibizumab groups, respectively. Twelve-week CST response was not strongly associated with 2-year outcomes.
A suboptimal response at 12 weeks did not preclude meaningful vision improvement (ie, ≥ 10-letter gain) in many eyes at 2 years. Eyes with less than 5-letter gain at 12 weeks often had good VA at 2 years without switching therapies.
•Early visual response to anti-VEGF for diabetic macular edema is associated with later vision outcomes.•Limited 12-week vision gain did not preclude meaningful 2-year gain in many eyes.•Eyes with < 5-letter 12-week gain typically had good (20/25–20/32) 2-year vision.•Results do not support switching from this DRCR.net anti-VEGF regimen over 2 years.•Studies of switching regimens should be compared with this DRCR.net anti-VEGF regimen.
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