Suzann Pershing

Cost-Effectiveness of Treatment of Diabetic Macular Edema

Context Current therapies for diabetic macular edema include laser treatment, intraocular injections of triamcinolone or drugs that inhibit vascular endothelial growth factor (VEGF), and combinations of laser treatment plus injections of triamcinolone or a VEGF inhibitor. Contribution The investigators compared the lifetime costs and effectiveness of alternative treatments by using mathematical models that incorporated what was already known about each treatment. Caution Long-term outcome data are limited. Implication The most effective treatment of diabetic macular edema is VEGF inhibitor injection with or without laser treatment. This therapy is as cost-effective as acceptable treatments for many other conditions. The Editors Diabetes affects approximately 26 million patients in the United States, accounts for

Risk Factors Predictive of Endogenous Endophthalmitis Among Hospitalized Patients With Hematogenous Infections in the United States

1 in

Defining a Minimum Set of Standardized Patient-centered Outcome Measures for Macular Degeneration

10 spent on health care, and is the leading cause of new-onset blindness among adults (1). Dilated eye examinations identify diabetic retinopathy, which ranges from mild (retinal hemorrhages) to severe (ischemia-induced neovascularization and fibrovascular proliferation, with potential hemorrhage, retinal detachment, or glaucoma). These examinations also identify diabetic macular edema (DME), which is central retinal edema resulting from increased vascular permeability of the retina. Diabetic macular edema affects central vision and is the most common cause of vision loss in patients with diabetes (2). Its prevalence is 9% among these patients (3), with approximately 75 000 new cases annually (4). Untreated DME can cause progressive vision decline (5) and medical costs that are 29% higher than those for unaffected patients with diabetes (6). The goal of DME treatment is to stop decline and, ideally, to recover vision. Successful treatment can enable a patient to resume driving, depending on the degree of vision impairment. Standard therapy has been macular laser treatment, which targets leaking microaneurysms and mildly stimulates subretinal cells to decrease edema. More recently, treatment of this condition has included intravitreal (intraocular) injections of triamcinolone acetonide or vascular endothelial growth factor (VEGF) inhibitors, which reduce vascular permeability and allow fluid reabsorption. Unlike laser treatment, which has potentially long-lasting effects, injections require periodic retreatment. Vascular endothelial growth factor inhibitors include bevacizumab, ranibizumab, and the newer VEGF Trap-Eye (aflibercept). In contrast to monotherapy, combination therapies of laser treatment and intravitreal injections aim to provide the long-term benefits of laser treatment and short-term benefits of fluid reabsorption. Treatment costs per injection differ substantially, from approximately

A Proposed Minimum Standard Set of Outcome Measures for Cataract Surgery

50 (off-label bevacizumab) to

Ocular hypertension and intraocular pressure asymmetry after intravitreal injection of anti-vascular endothelial growth factor agents.

1200 (U.S. Food and Drug Administrationapproved ranibizumab) (711). Each strategy is well-studied, but no trial compares all therapies and few compare costs. Evidence on cost-effectiveness is conflicting. The U.K.s National Institute for Health and Clinical Excellence evaluated an industry-conducted modeling analysis of ranibizumab, and it found the cost-effectiveness of VEGF inhibitors to be unconvincing relative to that of laser treatment (12). Two published studies reached the opposite conclusion; however, they did not consider lifetime costs and benefits nor compare all major treatments (13, 14). Our study compares 6 strategies for lifetime management of DME. By comparing therapy with no treatment, we evaluate the societal effect of undiagnosed DME, which is particularly important given the increasing prevalence of diabetes. Diagnosis and proper management of DME depends on appropriate referral from primary care clinicians, who also play an important role in shared decision making with patients. Building on a relationship of long-standing trust with their primary care providers, patients often seek advice and second opinions about treatments offered by specialists. Understanding the options, vision benefits, and tradeoffs in therapy for DME will support and inform such conversations as part of comprehensive diabetes care. Methods Overview We developed a decision-analytic Markov cohort model of the natural history and treatment of DME, integrating mortality, visual acuity, treatment costs, complications, and societal costs. The model compared the effect on health, longevity, and costs of the following management strategies: no treatment; monotherapy with a VEGF inhibitor (ranibizumab, 0.3 mg); monotherapy with triamcinolone, 4 mg; laser monotherapy; combination therapy with laser treatment plus a VEGF inhibitor; and combination therapy with laser treatment plus triamcinolone. We translated vision and complications into utility-based quality-of-life measures and analyzed these from a societal perspective, broadly considering all lifetime costs and benefits, regardless of who benefited (1520). Patient Cohort The main cohort included patients with type 1 or 2 diabetes and clinically significant DME. In the model, 50% were men, age was 63 years, and visual acuity of the better eye was 20/63. Patients had no previous cataract surgery and did not receive treatment of DME within 4 months. These characteristics were similar to those of the baseline populations of major clinical trials of DME (2133). Disease Progression Health states of DME reflected vision (visual acuity categories 1 through 6 [Table 1]), treatment status, and complications (Figure 1). Because longitudinal data on the natural history of progression of DME are limited, we used expert opinion and calibration to the DRCR.net (Diabetic Retinopathy Clinical Research Network) study cohort to estimate long-term changes without treatment (transition probabilities were calculated using a Markov model with constant progression rates [Supplement]) (34). Table 2 shows input values (see Table 4 of the Supplement for visual acuity outcomes with and without treatment and Table 23 of the Supplement for uncertainty ranges). Supplement. Cost-Effectiveness of Treatment of DME Table 1. Definition of Visual Acuity Categories Used in the Model Figure 1. Markov model schematic. The 6 alternatives to the right of the decision node (square box) represent the 6 strategies for comparison, each progressing within the Markov model. The shaded boxes represent the Markov model transitions for progression of diabetic macular edema. Visual acuity categories 1 through 6 represent states of visual acuity (Table 1). Solid arrows represent possible worsening (progression) within a given month, and dashed arrows represent the potential for improvement or progression within a given month while receiving treatment. On-treatment states are subject to risk for complications (arterial thromboembolic events, glaucoma, cataracts, and other major or minor complications). In the base case, treatment was stopped after 1 y for all strategies or sooner if an arterial thromboembolic event or severe glaucoma occurred. VEGF = vascular endothelial growth factor.* Off or after treatment. Table 2. Base-Case Model Inputs* Treatment Effectiveness and Complications Primary data sources were the multicenter, randomized, double-masked clinical trials RESTORE (Ranibizumab Monotherapy or Combined With Laser Versus Laser Monotherapy for Diabetic Macular Edema) (21), DRCR.net (2226), READ-2 (Two-Year Outcomes of the Ranibizumab for Edema of the Macula in Diabetes) (27, 28), RISE (A Study of Ranibizumab Injection in Subjects With Clinically Significant Macular Edema With Center Involvement Secondary to Diabetes Mellitus) (29, 30), RIDE (A Study of Ranibizumab Injection in Subjects With Clinically Significant Macular Edema With Center Involvement Secondary to Diabetes Mellitus) (29, 30), RESOLVE (Safety and Efficacy of Ranibizumab in Diabetic Macular Edema) (31), and ETDRS (Early Treatment Diabetic Retinopathy Study) (32, 33), totaling 5009 patients. Patient characteristics reasonably reflected those in general clinical practice; however, patients in clinical trials had more homogeneous vision impairment and better-controlled diabetes. Dosage, treatment frequency, and follow-up also vary in practice. We used smaller studies in sensitivity analyses to explore these differences (4457). We modeled key complications individually: arterial thromboembolic events, glaucoma (controlled and severe or uncontrolled), and cataracts. We divided complications into major (for example, endophthalmitis) and minor (for example, eye irritation) categories (Supplement). We captured 1-time costs and quality-of-life decrements for acute complications and monthly costs and quality-of-life decrements for chronic complications (Table 2). In the main analysis, we assumed treatment of the better eye for a direct and predictable effect on vision-related quality of life. Treatment was received for 1 year except when stopped earlier because of complications (arterial thromboembolic events or uncontrolled glaucoma). We calibrated the model to match the average and the distribution of number of treatments for each strategy in clinical trials (Supplement). We selected a 1-year treatment period for consistency with primary trial end points and because greater crossover among treatment groups occurred in extended 2- and 3-year follow-up. For progression of DME after treatment, we modeled visual decline at a slower rate in strategies involving laser treatment (because clinical benefit from this therapy can be long-standing, in contrast to the short-term effect of injections) (58). We evaluated each assumption in sensitivity analyses. Additional simplifying assumptions included no crossover among treatments and no treatment resumption once a treatment had been discontinued (because of an arterial thromboembolic event or uncontrolled glaucoma orin the main analysisafter 1 year of therapy). We made these assumptions to keep the modeling tractable and because of limited data (Supplement). We validated clinical

Phacoemulsification versus extracapsular cataract extraction: where do we stand?

PURPOSE To identify potential risk factors associated with endogenous endophthalmitis among hospitalized patients with hematogenous infections. DESIGN Retrospective cross-sectional study. METHODS MarketScan Commercial Claims and Encounters, and Medicare Supplemental and Coordination of Benefit inpatient databases from the years 2007-2011 were obtained. Utilizing ICD-9 codes, logistic regression was used to identify potential predictors/comorbidities for developing endophthalmitis in patients with hematogenous infections. RESULTS Among inpatients with hematogenous infections, the overall incidence rate of presumed endogenous endophthalmitis was 0.05%-0.4% among patients with fungemia and 0.04% among patients with bacteremia. Comorbid human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) (OR = 4.27; CI, 1.55-11.8; P = .005), tuberculosis (OR = 8.5; CI, 1.2-61.5; P = .03), endocarditis (OR = 8.3; CI, 4.9-13.9; P < .0001), bacterial meningitis (OR = 3.8; CI, 1.2-12.0; P = .023), fungal meningitis (OR = 59.1; CI, 14.1-247.8; P < .0001), internal organ abscess (OR = 2.9; CI, 1.2-6.4; P = .02), lymphoma/leukemia (OR = 2.9; CI, 1.6-5.3; P < .0001), skin abscess/cellulitis (OR = 1.75; CI, 1.1-2.8; P = .02), pyogenic arthritis (OR = 4.2; CI, 1.8-9.6; P = .001), diabetes with ophthalmic manifestations (OR = 7.0; CI, 1.7-28.3; P = .006), and urinary tract infection (OR = 0.04; CI, 0.3-0.9; P = .023) were each significantly associated with a diagnosis of endogenous endophthalmitis. Patients aged 0-17 years (OR = 2.61; CI, 1.2-5.7; P = .02), 45-54 years (OR = 3.4; CI, 2.0-5.4; P < .0001), and 55-64 years (OR = 2.9; CI, 1.8-4.8; P < .0001); those having length of stay of 3-10 days (OR = 1.9; CI, 1.1-3.3; P = .01), 11-30 days (OR = 3.1; CI, 1.8-5.5; P < .0001), and 31+ days (OR = 5.3; CI, 2.7-10.4; P < .0001); and those with intensive care unit/neonatal intensive care unit (ICU/NICU) admissions (OR = 1.5; CI, 1.4-1.6; P < .0001) were all more likely to be diagnosed with endogenous endophthalmitis. CONCLUSIONS Endogenous endophthalmitis is rare among hospitalized patients in the United States. Among patients with hematogenous infections, odds of endogenous endophthalmitis were higher for children and middle-aged patients, and for patients with endocarditis, bacterial meningitis, lymphoma/leukemia, HIV/AIDS, internal organ abscess, diabetes with ophthalmic manifestations, skin cellulitis/abscess, pyogenic arthritis, tuberculosis, longer hospital stays, and/or ICU/NICU admission.

Association of Vision Loss With Cognition in Older Adults

PURPOSE To define a minimum set of outcome measures for tracking, comparing, and improving macular degeneration care. DESIGN Recommendations from a working group of international experts in macular degeneration outcomes registry development and patient advocates, facilitated by the International Consortium for Health Outcomes Measurement (ICHOM). METHODS Modified Delphi technique, supported by structured teleconferences, followed by online surveys to drive consensus decisions. Potential outcomes were identified through literature review of outcomes collected in existing registries and reported in major clinical trials. Outcomes were refined by the working group and selected based on impact on patients, relationship to good clinical care, and feasibility of measurement in routine clinical practice. RESULTS Standardized measurement of the following outcomes is recommended: visual functioning and quality of life (distance visual acuity, mobility and independence, emotional well-being, reading and accessing information); number of treatments; complications of treatment; and disease control. Proposed data collection sources include administrative data, clinical data during routine clinical visits, and patient-reported sources annually. Recording the following clinical characteristics is recommended to enable risk adjustment: age; sex; ethnicity; smoking status; baseline visual acuity in both eyes; type of macular degeneration; presence of geographic atrophy, subretinal fibrosis, or pigment epithelial detachment; previous macular degeneration treatment; ocular comorbidities. CONCLUSIONS The recommended minimum outcomes and pragmatic reporting standards should enable standardized, meaningful assessments and comparisons of macular degeneration treatment outcomes. Adoption could accelerate global improvements in standardized data gathering and reporting of patient-centered outcomes. This can facilitate informed decisions by patients and health care providers, plus allow long-term monitoring of aggregate data, ultimately improving understanding of disease progression and treatment responses.

Cataract Surgery Complications and Revisit Rates Among Three States

IMPORTANCE Aligning outcome measures for cataract surgery, one of the most frequently performed procedures globally, may facilitate international comparisons that can drive improvements in the outcomes most meaningful to patients. OBJECTIVE To propose a minimum standard set of outcome measures for cataract surgery that enables global comparisons. DESIGN, SETTING, AND PARTICIPANTS A working group of international experts in cataract outcomes and registries was convened, along with a patient advocate, to agree on a consensus of outcome measures for cataract surgery. In a modified Delphi process, the group met regularly between November 10, 2012, and November 21, 2013, to discuss which outcomes to include in a standard set. Included factors were based on extant literature, existing registries, and the experience of group members. Similarly, a series of consensus discussions were held to determine a set of risk factors to be gathered for each patient. The final shortlist was compiled into a standard set. Analysis was performed from November 22, 2013, to April 5, 2014. MAIN OUTCOMES AND MEASURES Development of a recommended standard set encompassing preoperative metrics including patient risk factors, intraoperative factors including surgical complications, and postoperative cataract surgery outcomes. RESULTS The recommended standard set encompasses all patients treated for cataracts by 1 of 4 surgical approaches (phacoemulsification, sutured manual extracapsular cataract extraction, sutureless manual extracapsular cataract extraction, or intracapsular cataract extraction). The recommended metrics to be recorded preoperatively include demographics, ocular history and comorbidities, preoperative visual acuity, and patient-reported visual function. The recommended outcomes were split into intraoperative and postoperative metrics. Intraoperative outcomes include capsule-related problems, dislocation of lens nucleus fragments into the vitreous, and other complications. Postoperative outcomes include visual acuity, refractive error, patient-reported visual function, and early and late complications of surgery. The suggested follow-up for collection of postoperative outcomes is up to 3 months. CONCLUSIONS AND RELEVANCE A minimum standard set of outcome measures for cataract surgery is important for meaningful comparison across contexts. The proposed data set is a compromise between all useful data and the practicalities of data collection.

Supply and Perceived Demand for Teleophthalmology in Triage and Consultations in California Emergency Departments.

BACKGROUND AND OBJECTIVE To evaluate elevated intraocular pressure (IOP) after intravitreal injections of vascular endothelial growth factor (VEGF) inhibitors and contribute toward the recognition and understanding of its mechanisms, pattern, and treatment. PATIENTS AND METHODS Retrospective case series of VEGF-inhibitor injections at two academic centers (Stanford University and Mayo Clinic) over 4 years. Cases were evaluated for IOP elevation (≥ 24 mm Hg) or asymmetry (≥ 3 mm Hg IOP difference between eyes on three visits). RESULTS Twenty-one eyes were identified with pathologically elevated IOP after treatment. Most had delayed-onset (average: 15 months after treatment, after 10 injections) elevation. IOP-lowering therapy was required in 81%. More consecutive visits with IOP asymmetry occurred in patients developing ocular hypertension (11.1% pre-diagnosis vs 66.7% post-diagnosis; OR = 9.00, P = .003). CONCLUSION Elevated IOP may occur after ranibizumab or bevacizumab injections, often exhibiting a delayed and perhaps cumulative effect. The authors found significant bilateral IOP asymmetry in patients developing unilateral glaucoma after VEGF-inhibitor injections, a potential early indicator or proxy for pathologic IOP elevation.

Predictive modeling of risk factors and complications of cataract surgery.

Purpose of review Cataract surgery at present is divisible into two general techniques: manual extracapsular cataract extraction and phacoemulsification – with ECCE further separated into the traditional form and small-incision cataract surgery. This review will discuss updates in surgical techniques, outcome comparisons, cost analysis, and the continued role of extracapsular cataract extraction in Western countries. Recent findings Surgical techniques for manual extracapsular cataract extraction have undergone much refinement, with numerous descriptions of techniques in a recent literature. Studies that have emerged in the last several years allow us to compare surgical results between different techniques and suggest that there is little difference in final outcome when each surgery is done well. Overall cost–effectiveness and suitability of each technique vary based on location and facilities. Summary Manual extracapsular cataract extraction (especially small-incision versions) occupies an important place in modern cataract surgery, and, while not a replacement for phacoemulsification in Western countries, should be part of a cataract surgeons overall skill set.