To characterize the first 10 years of intravitreal anti-vascular endothelial growth factor (VEGF) medication use for ophthalmic disease, including bevacizumab, ranibizumab, and aflibercept.
A ...retrospective cohort study using administrative claims data from January 1, 2006 to December 31, 2015.
Total of 124 835 patients 18 years of age or over in the United States.
OptumLabs Data Warehouse, which includes administrative claims data for over 100 million commercially insured and Medicare Advantage individuals, was used to identify patients receiving intravitreal anti-VEGF injections based on Current Procedural Terminology codes.
Total and annual numbers of intravitreal anti-VEGF injections, as well as injections per 1000 enrolled patients per general category of ophthalmic disease, overall and for each available medication.
There were 959 945 anti-VEGF injections among 124 835 patients from 2006 to 2015. Among all injections, 64.6% were of bevacizumab, 22.0% ranibizumab, and 13.4% aflibercept; 62.7% were performed to treat age-related macular degeneration (AMD), 16.1% to treat diabetic retinal diseases (including 0.9% of all injections that were for proliferative diabetic retinopathy), 8.3% to treat retinal vein occlusions, and 12.9% for all other uses. Use of bevacizumab and ranibizumab for AMD plateaued as of 2011/2012 and decreased thereafter (in 2006, 58.8 and 35.3 injections/1000 AMD patients, respectively; in 2015, 294.4 and 100.7 injections/1000), whereas use of aflibercept increased (1.1 injections/1000 AMD patients in 2011 to 183.0 injections/1000 in 2015). Bevacizumab use increased each year for diabetic retinal disease (2.4 injections/1000 patients with diabetic retinal disease in 2009 to 13.6 per 1000 in 2015) while that of ranibizumab initially increased significantly and then declined after 2014 (0.1 in 2009 to 4.0 in 2015). Aflibercept use increased each year in patients with diabetic retinal diseases and retinal vein occlusions (both <0.1 per 1000 retinal vein occlusion patients in 2011, 5.6 and 140.2 in 2015).
Intravitreal injections of anti-VEGF medications increased annually from 2006 to 2015. Bevacizumab was the most common medication used, despite its lacking U.S. Food and Drug Administration approval to treat ophthalmic disease, and AMD was the most common condition treated. Ranibizumab use declined after 2014 while both the absolute and relative use of bevacizumab and aflibercept increased.
The Diabetes Control and Complications Trial (DCCT) demonstrated that intensive therapy reduced the development and progression of retinopathy in type 1 diabetes (T1D) compared with conventional ...therapy. The Epidemiology of Diabetes Interventions and Complications (EDIC) study observational follow-up showed persistent benefits. In addition to glycemia, we now examine other potential retinopathy risk factors (modifiable and nonmodifiable) over more than 30 years of follow-up in DCCT/EDIC.
The retinopathy outcomes were proliferative diabetic retinopathy (PDR), clinically significant macular edema (CSME), and ocular surgery. The survival (event-free) probability was estimated using the Kaplan-Meier method. Cox proportional hazards models assessed the association between risk factors and subsequent risk of retinopathy. Both forward- and backward-selection approaches determined the multivariable models.
Rate of ocular events per 1,000 person-years was 12 for PDR, 14.5 for CSME, and 7.6 for ocular surgeries. Approximately 65%, 60%, and 70% of participants remained free of PDR, CSME, and ocular surgery, respectively. The greatest risk factors for PDR in descending order were higher mean HbA
, longer duration of T1D, elevated albumin excretion rate (AER), and higher mean diastolic blood pressure (DBP). For CSME, risk factors, in descending order, were higher mean HbA
, longer duration of T1D, and greater age and DBP and, for ocular surgeries, were higher mean HbA
, older age, and longer duration of T1D.
Mean HbA
was the strongest risk factor for the progression of retinopathy. Although glycemic control is important, elevated AER and DBP were other modifiable risk factors associated with the progression of retinopathy.
To estimate geographic variation of intravitreal injection rates and Medicare anti-vascular endothelial growth factor (VEGF) drug costs per injection in aging Americans.
Observational cohort study ...using 2013 Medicare claims database.
United States fee-for-service (FFS) Part B Medicare beneficiaries and their providers.
Medicare Provider Utilization and Payment Data furnished by the Centers for Medicare and Medicaid Services was used to identify all intravitreal injection claims and anti-VEGF drug claims among FFS Medicare beneficiaries in all 50 states and the District of Columbia in 2013. The rate of FFS Medicare beneficiaries receiving intravitreal injections and the mean Medicare-allowed drug payment per anti-VEGF injection was calculated nationally and for each state. Geographic variations were evaluated by using extremal quotient, coefficient of variation, and systematic component of variance (SCV).
Rate of FFS Medicare Part B beneficiaries receiving intravitreal injections (Current Procedural Terminology CPT code, 67028), nationally and by state; mean Medicare-allowed drug payment per anti-VEGF injection (CPT code, 67028; and treatment-specific J-codes, J0178, J2778, J9035, J3490, and J3590) nationally and by state.
In 2013, the rate of FFS Medicare beneficiaries receiving intravitreal injections varied widely by 7-fold across states (range by state, 4 per 1000 Wyoming-28 per 1000 Utah), averaging 19 per 1000 beneficiaries. The mean SCV was 8.5, confirming high nonrandom geographic variation. There were more than 2.1 million anti-VEGF drug claims, totaling more than $2.3 billion in Medicare payments for anti-VEGF agents in 2013. The mean national Medicare drug payment per anti-VEGF injection varied widely by 6.2-fold across states (range by state, $242 South Carolina-$1509 Maine), averaging $1078 per injection. Nationally, 94% of injections were office based and 6% were facility based.
High variation was observed in intravitreal injection rates and in Medicare drug payments per anti-VEGF injection across the United States in 2013. Identifying factors that contribute to high variation may help the ophthalmology community to optimize further the delivery and use of anti-VEGF agents.
IMPORTANCE: Despite the increasing prevalence of type 2 diabetes (T2D) diagnosed in childhood, little is known about the natural history of ocular sequelae in youth-onset T2D compared with type 1 ...diabetes (T1D). OBJECTIVE: To assess the risk of developing diabetes-associated ocular complications among youth diagnosed with diabetes. DESIGN, SETTING, AND PARTICIPANTS: This retrospective, population-based medical record review included all residents of Olmsted County, Minnesota (95.7% White in 1990), diagnosed with diabetes at younger than 22 years (hereinafter referred to as children) from January 1, 1970, through December 31, 2019. MAIN OUTCOMES AND MEASURES: Risk of developing ocular complications over time. RESULTS: Among 1362 individuals with a diagnostic code of diabetes, medical record reviews confirmed a diagnosis of T1D or T2D in 606 children, of whom 525 (86.6%) underwent at least 1 eye examination (mean SD age at diabetes diagnosis, 12.1 5.4 years; 264 50.3% male). Diabetes-associated ocular complications occurred in 147 of the 461 children (31.2%) with T1D and in 17 of the 64 children (26.6%) with T2D. The hazard ratio illustrating the risk between T2D and T1D rates was 1.88 (95% CI, 1.13-3.12; P = .02) for developing any diabetic retinopathy (nonproliferative or greater), 2.33 (95% CI, 0.99-5.50; P = .048) for proliferative diabetic retinopathy, 1.49 (95% CI, 0.46-4.89; P = .50) for diabetic macular edema, 2.43 (95% CI, 0.54-11.07; P = .24) for a visually significant cataract, and 4.06 (95% CI, 1.34-12.33; P = .007) for requiring pars plana vitrectomy by 15 years after the diagnosis of diabetes. CONCLUSIONS AND RELEVANCE: Diabetic retinopathy, proliferative diabetic retinopathy, and the need for pars plana vitrectomy occurred within a shorter diabetes duration for children with T2D compared with T1D in this population-based cohort. Children with T2D had almost twice the risk of developing retinopathy compared with those with T1D. These findings suggest that to prevent serious ocular complications, children with T2D may require ophthalmoscopic evaluations at least as frequently as or more frequently than children with T1D.
To investigate the outcomes of cataract surgery in patients with active diabetic macular edema (DME) who are receiving active treatment with intravitreal anti–vascular endothelial growth factor ...(VEGF) injections in the perioperative period.
Retrospective clinical cohort study.
We reviewed all patients who underwent cataract surgery and were receiving intravitreal anti-VEGF injections from January 1, 2012 through December 31, 2017. Thirty-seven eyes underwent cataract surgery and received ≥1 intravitreal anti-VEGF injection for a diagnosis of DME within 6 months before surgery. Outcome measures included the development of subretinal or intraretinal fluid in the 6 months after surgery, timing of injections, number of injections, best-corrected visual acuity, and central subfield thickness.
There was a significant improvement between pre- and postoperative best-corrected visual acuity when comparing all eyes (Ps < .0001) and no significant difference in central subfield thickness before and after surgery (P > .05). There were 30 eyes (81.1%) that had fluid on the preoperative optical coherence tomography scan. Seventeen eyes (45.9%) developed new or worsening postoperative DME. Comparing the eyes that did or did not develop worsening DME, there were no differences in postoperative visual acuities (P > .05). Eyes that did develop new fluid had significant increases in postoperative central subfield thickness at both 1 month (350 vs 320 μm, P = .036) and 6 months (342 vs 305 μm, P = .013).
In a real-world setting, patients with cataracts and actively treated DME may undergo cataract surgery but may see a worsening of DME not immediately affecting the best-corrected visual acuity.
To examine real-world telemedicine outcomes of diabetic retinopathy (DR) screening with artificial intelligence (AI)-based image analysis, reflex dilation, and secondary image overread in a primary ...care setting.
Validity and reliability analysis.
Single institution review of 1052 consecutive adult patients who received diabetic retinopathy photoscreening in the primary care setting over an 18-month period. Nonmydriatic fundus photographs were acquired and analyzed by the IDx-DR AI-based system. When nonmydriatic images were ungradable, reflex dilation (1% tropicamide) and mydriatic photography were performed for repeat AI-based analysis. Manual overread was performed on all images. Patient demographics, clinical characteristics, and screening outcomes were recorded.
A total of 965 of 1052 patients (91.7%) had AI-gradable fundus photographs: 580 had gradable nonmydriatic imaging (55.1%) and 440 of 472 patients with ungradable nonmydriatic photographs had reflex dilation (93.2%). One hundred thirty-eight of 965 patients (14.3%) were AI-graded as “positive” (greater than mild NPDR) and 827 of 965 were “negative” (85.7%), with 100% sensitivity (95% CI 90.8-100%), 89.2% specificity (95% CI 87.0-91.1%), 27.5% positive predictive value (95% CI 24.0-31.4%), and 100% negative predictive value (95% CI 99.6-100%) compared with manual overread assessment of greater than mild NPDR requiring further evaluation with a comprehensive dilated examination. Image gradeability was inversely related to patient age: 93.5% gradable (61.9% nonmydriatic) for patients aged <70 years vs 85.3% (31.0% nonmydriatic) for patients aged 70+ years (P < .001).
Incorporation of AI-based image analysis into real-world primary care diabetic retinopathy screening yielded no false negative results and offered excellent image gradeability within a protocol combining nonmydriatic fundus photography and pharmacologic dilation, as needed. Image gradeability was lower with increasing patient age.
To investigate the outcomes of patients with exudative age-related macular degeneration (AMD) treated with intravitreal antivascular endothelial growth factors (VEGF) using a telemedicine system.
...Interventional case series.
This study examined all patients with exudative AMD who were receiving intravitreal anti-VEGF injections from September 1, 2015, through August 31, 2017, using electronic consultations at a single academic center and health system. Patients were managed initially by a retinal specialist and then allowed to receive further care with their local ophthalmologist. There were 200 electronic consultations placed during this time period for 83 eyes of 59 patients. Data collected included the retina specialist's recommendations: intravitreal agent, interval between injections, number of injections, and when the patient was to follow-up. All occurrences of recommendations that were not completed were reported.
The mean age of the patients at the time of electronic consultations was 82.3 ± 7.3 years with a mean follow-up time of 2.4 ± 0.81 years. The mean distance from the home of the patient to the retina specialist was 70 ± 44 miles. There were 14 consultations (7.1%) that did not comply with the recommendations of the retina specialist. Most of these were due to other medical comorbidities leading to missed appointments or scheduling errors.
In an integrated health care setting, 59 patients with exudative AMD were identified who were able to be effectively managed using a telemedicine system. In the appropriate setting, telemedicine may be able to assist in the management of patients with wet AMD.
Although the literature on childhood diabetes has traditionally focused on Type 1 diabetes (T1D), youth-onset Type 2 diabetes (T2D) and its associated morbidities have become increasingly prevalent. ...This study reports on the incidence and demographics of a population-based cohort of children diagnosed with diabetes over a 50-year period.AIMSAlthough the literature on childhood diabetes has traditionally focused on Type 1 diabetes (T1D), youth-onset Type 2 diabetes (T2D) and its associated morbidities have become increasingly prevalent. This study reports on the incidence and demographics of a population-based cohort of children diagnosed with diabetes over a 50-year period.Medical records of patients < 22 years diagnosed with diabetes from January 1, 1970, through December 31, 2019, were retrospectively reviewed using the Rochester Epidemiology Project, a database of clinics and hospitals in Olmsted County, Minnesota.METHODSMedical records of patients < 22 years diagnosed with diabetes from January 1, 1970, through December 31, 2019, were retrospectively reviewed using the Rochester Epidemiology Project, a database of clinics and hospitals in Olmsted County, Minnesota.Of 606 children diagnosed with diabetes, 519 (85.6%) were diagnosed with T1D at a mean age of 10.9 ± 5.3 years. 87 (14.4%) were diagnosed with T2D at a mean age of 17.4 ± 3.4 years. The incidence of T2D increased 23-fold (p < 0.001) over the five-decade period (5 per 100,000 children/year) while T1D remained stable (26 per 100,000 children/year; p = 0.08). The mean body mass index at T2D diagnosis (35.5 kg/m2 ± 10.4) was significantly higher than in T1D (18.9 kg/m2 ± 4.6 95% CI for difference 14.2-19.0; p < 0.0001). Sixty-nine percent of children diagnosed with T2D were female, and the hazard ratio of developing diabetic retinopathy in females with T2D compared to males was 6.83 (95% CI 1.53-30.44; p = 0.012).RESULTSOf 606 children diagnosed with diabetes, 519 (85.6%) were diagnosed with T1D at a mean age of 10.9 ± 5.3 years. 87 (14.4%) were diagnosed with T2D at a mean age of 17.4 ± 3.4 years. The incidence of T2D increased 23-fold (p < 0.001) over the five-decade period (5 per 100,000 children/year) while T1D remained stable (26 per 100,000 children/year; p = 0.08). The mean body mass index at T2D diagnosis (35.5 kg/m2 ± 10.4) was significantly higher than in T1D (18.9 kg/m2 ± 4.6 95% CI for difference 14.2-19.0; p < 0.0001). Sixty-nine percent of children diagnosed with T2D were female, and the hazard ratio of developing diabetic retinopathy in females with T2D compared to males was 6.83 (95% CI 1.53-30.44; p = 0.012).The incidence of youth-onset T2D increased significantly over the 50-year period while the incidence of T1D remained stable. A higher proportion of females were diagnosed with youth-onset T2D. Females with T2D were more than six times likelier to develop diabetic retinopathy than males.CONCLUSIONSThe incidence of youth-onset T2D increased significantly over the 50-year period while the incidence of T1D remained stable. A higher proportion of females were diagnosed with youth-onset T2D. Females with T2D were more than six times likelier to develop diabetic retinopathy than males.
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