Development, Validation, and Innovation in Ophthalmic Laser-Based Imaging: Report From a US Food and Drug Administration-Cosponsored Forum.

In April 2019, the US Food and Drug Administration, in conjunction with 11 professional ophthalmic, vision science, and optometric societies, convened a forum on laser-based imaging. The forum brought together the Food and Drug Administration, clinicians, researchers, industry members, and other stakeholders to stimulate innovation and ensure that patients in the US are the first in the world to have access to high-quality, safe, and effective medical devices. This conference focused on the technology, clinical applications, regulatory issues, and reimbursement issues surrounding innovative ocular imaging modalities. Furthermore, the emerging role of artificial intelligence in ophthalmic imaging was reviewed. This article summarizes the presentations, discussion, and future directions.

Billing of cataract surgery as complex versus routine for Medicare beneficiaries.

PURPOSE: To estimate ophthalmologist-level variation in cataract surgery billing and evaluate patient and ophthalmologist characteristics associated with complex cataract surgery coding. SETTING: Cross-sectional study. DESIGN: Retrospective case series. METHODS: Medicare beneficiaries aged 65 years or older who had cataract surgery between January 1, 2016, and December 31, 2017, were included. Billing of cataract surgery as complex versus routine and patient and physician characteristics associated with billing of cataract surgery as complex were evaluated. RESULTS: An estimated 3.5 million cataract procedures were performed on Medicare beneficiaries in 2016 and 2017. Men (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.75-1.82), patients 75 years or older (versus those aged 65 to 74 years: OR, 1.35; 95% CI, 1.33-1.36), and racial minorities (blacks versus whites: OR, 1.80; 95% CI, 1.75-1.85) had increased odds of having cataract surgery coded as complex. The mean rate of coding for complex cataract surgery by individual surgeons (n = 10 075) in the United States was 11.2%, with significant variation. A high-risk clinical diagnosis code was associated with 40.0% of complex cataract surgeries. Adjusted for patient characteristics, ophthalmologists who graduated from medical school within the past 10 years (OR, 1.35; 95% CI, 1.22-1.49) were more likely to code for complex cataract surgery. Higher volume ophthalmologists were less likely to code for complex cataract surgery than low-volume ophthalmologists. CONCLUSIONS: There was marked variation among ophthalmologists in the use of complex cataract surgery. Some variability might represent inaccurate coding and was not entirely based on differences in referral patterns for more complex patients.

Safety and Efficacy of Anti-Vascular Endothelial Growth Factor Therapies for Neovascular Age-Related Macular Degeneration: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the evidence on the safety and efficacy of anti-vascular endothelial growth factor (VEGF) therapies for the treatment of neovascular age-related macular degeneration (AMD). METHODS: A literature search of the PubMed and Cochrane Library databases was last conducted in February 2017; there were no date restrictions, and the search was limited to studies published in English. The combined searches yielded 191 citations, 28 of which were selected because they were clinical trials and were deemed clinically relevant for the Ophthalmic Technology Assessment Committee Retina/Vitreous Panel to review in full. The panel methodologist then assigned a level of evidence rating to each study. RESULTS: Sixteen of the 28 citations provided level I evidence supporting the use of anti-VEGF agents for neovascular AMD, including intravitreal ranibizumab, aflibercept, and bevacizumab. Eight studies reviewed provided level II evidence, and 4 studies provided level III evidence, but only the level I studies are included in this assessment. There are long-term follow-up data on the efficacy of ranibizumab and bevacizumab (≥5 years), but these data are subject to the bias of incomplete follow-up. CONCLUSIONS: Review of the literature indicates that intravitreal injection of anti-VEGF therapy is safe and effective for neovascular AMD over 2 years, the period for which data are available. Further research is needed to evaluate the long-term safety and comparative efficacy of these agents.

Therapies for Macular Edema Associated with Branch Retinal Vein Occlusion: A Report by the American Academy of Ophthalmology.

PURPOSE: To evaluate the available evidence on the ocular safety and efficacy of current therapeutic alternatives for the management of macular edema (ME) secondary to branch retinal vein occlusion (BRVO). METHODS: Literature searches were last conducted on January 31, 2017, in PubMed with no date restrictions and limited to articles published in English, and in the Cochrane Database without language limitations. The searches yielded 321 citations, of which 109 were reviewed in full text and 27 were deemed appropriate for inclusion in this assessment. The panel methodologist assigned ratings to the selected studies according to the level of evidence. RESULTS: Level I evidence was identified in 10 articles that addressed anti-vascular endothelial growth factor (VEGF) pharmacotherapies for ME, including intravitreal bevacizumab (5), aflibercept (2), and ranibizumab (4). Level I evidence was identified in 6 studies that examined intravitreal corticosteroids, including triamcinolone (4) and the dexamethasone implant (2). Level I evidence also was available for the role of macular grid laser photocoagulation (7) and scatter peripheral laser surgery (1). The inclusion of level II and level III studies was limited given the preponderance of level I studies. The number of studies on combination therapy is limited. CONCLUSIONS: Current level I evidence suggests that intravitreal pharmacotherapy with anti-VEGF agents is effective and safe for ME secondary to BRVO. Prolonged delay in treatment is associated with less improvement in visual acuity (VA). Level I evidence also indicates that intravitreal corticosteroids are effective and safe for the management of ME associated with BRVO; however, corticosteroids are associated with increased potential ocular side effects (e.g., elevated intraocular pressure, cataracts). Laser photocoagulation remains a safe and effective therapy, but VA results lag behind the results for anti-VEGF therapies.

Diagnosis and Treatment of Acute Retinal Necrosis: A Report by the American Academy of Ophthalmology.

PURPOSE: To evaluate the available evidence in peer-reviewed publications about the diagnosis and treatment of acute retinal necrosis (ARN). METHODS: Literature searches of the PubMed and Cochrane Library databases were last conducted on July 27, 2016. The searches identified 216 unique citations, and 49 articles of possible clinical relevance were reviewed in full text. Of these 49 articles, 27 were deemed sufficiently relevant or of interest, and they were rated according to strength of evidence. An additional 6 articles were identified from the reference lists of these articles and included. All 33 studies were retrospective. RESULTS: Polymerase chain reaction (PCR) testing of aqueous or vitreous humor was positive for herpes simplex virus (HSV) or varicella zoster virus (VZV) in 79% to 100% of cases of suspected ARN. Aqueous and vitreous specimens are both sensitive and specific. There is level II and III evidence supporting the use of intravenous and oral antiviral therapy for the treatment of ARN. Data suggest that equivalent plasma drug levels of acyclovir can be achieved after administration of oral valacyclovir or intravenous acyclovir. There is level II and III evidence suggesting that the combination of intravitreal foscarnet and systemic antiviral therapy may have greater therapeutic efficacy than systemic therapy alone. The effectiveness of prophylactic laser or early pars plana vitrectomy (PPV) in preventing retinal detachment (RD) remains unclear. CONCLUSIONS: Polymerase chain reaction testing of ocular fluid is useful in supporting a clinical diagnosis of ARN, but treatment should not be delayed while awaiting PCR results. Initial oral or intravenous antiviral therapy is effective in treating ARN. The adjunctive use of intravitreal foscarnet may be more effective than systemic therapy alone. The role of prophylactic laser retinopexy or early PPV is unknown at this time.

Differences in Clinical Activity and Medicare Payments for Female vs Male Ophthalmologists.

IMPORTANCE: The number of women in ophthalmology is rising. Little is known about their clinical activity and collections. OBJECTIVE: To examine whether charges, as reflected in reimbursements from the Centers for Medicare & Medicaid Services (CMS) to ophthalmologists, differ by sex and how disparity relates to differences in clinical activity. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of the CMS database for payments to ophthalmologists from January 1, 2012, through December 31, 2013. The dates of the analysis were February 1 through May 30, 2016. After exclusion of J and Q codes, the total payments to and the number of charges by individual ophthalmologists were analyzed. The mean values were compared using a single t test, and the medians were compared by the nonparametric Wilcoxon rank sum test. MAIN OUTCOMES AND MEASURES: Primary outcome measures were the mean and median CMS payments to male and female ophthalmologists in outpatient, non-facility-based settings. Secondary outcome measures included the number of charges submitted by men and women and the types of charges most commonly submitted by men and women. RESULTS: This study included 16 111 ophthalmologists (3078 women [19.1%] and 13 033 men [80.9%]) in 2012 and 16 179 ophthalmologists (3206 women [19.8%] and 12 973 men [80.2%]) in 2013. In 2012, the average female ophthalmologist collected $0.58 (95% CI, $0.54-$0.62; P < .001) for every dollar collected by a male ophthalmologist; comparing the medians, women collected $0.56 (95% CI, $0.50-$0.61; P < .001) for every dollar earned by men. Mean and median collections were similar when comparing female vs male ophthalmologists in 2013 (P < .001). The mean payment per charge was the same for men and women, $66 in 2012 and $64 in 2013. There was a strong association between collections and work product, with female ophthalmologists submitting fewer charges to Medicare in 2012 (median, 1120 charges; difference -935; 95% CI, -1024 to -846; P < .001) and in 2013 (median, 1141 charges; difference -937; 95% CI, -1026 to -848; P < .001) than male ophthalmologists. When corrected by comparing men and women with similar clinical activity, renumeration was still lower for women. In both years, women were underrepresented among ophthalmologists with the highest collections. CONCLUSIONS AND RELEVANCE: Remuneration from the CMS was disparate between male and female ophthalmologists in 2012 and 2013 because of the submission of fewer charges by women. Further studies are necessary to explore root causes for this difference, with equity in opportunity and parity in clinical activity standing to benefit the specialty.

Morphological assessment of the retina in uveitis.

BACKGROUND: The objective of this study is to describe a system for color photograph evaluation in uveitis and report baseline morphologic findings for the Multicenter Uveitis Steroid Treatment (MUST) Trial. Four-hundred seventy-nine eyes of 255 subjects with intermediate, posterior, and panuveitis had stereoscopic color fundus photographs obtained by certified photographers and evaluated by certified graders using standardized procedures to evaluate morphologic characteristics of uveitis. The posterior pole was evaluated for macular edema, vitreoretinal interface abnormalities, and macular pigment disturbance/atrophy; the optic disk was assessed for edema, pallor, or glaucomatous changes. The presence of neovascularization, vascular occlusion, vascular sheathing, and tractional retinal changes was determined. A random subset of 77 images was re-graded to determine the percentage agreement with the original grading on a categorical scale. RESULTS: At baseline, 437/479 eyes had images available to grade. Fifty-three eyes were completely ungradable due to media opacity. Common features of intermediate and posterior/panuveitis were epiretinal membrane (134 eyes, 35 %), and chorioretinal lesions (140 eyes, 36 %). Macular edema was seen in 16 %. Optic nerve head and vascular abnormalities were rare. Reproducibility evaluation found exact agreement for the presence of chorioretinal lesions was 78 %, the presence and location of macular edema was 71 %, and the presence of epiretinal membrane was 71 %. Vertical cup-to-disk ratio measurement had intra-class correlation of 0.75. CONCLUSIONS: The MUST system for evaluating stereoscopic color fundus photographs describes the morphology of uveitis and its sequelae, in a standardized manner, is highly reproducible, and allows monitoring of treatment effect and safety evaluation regarding these outcomes in clinical trials.

Prevalence of Noninfectious Uveitis in the United States: A Claims-Based Analysis.

IMPORTANCE: Noninfectious uveitis (NIU) is a collection of intraocular inflammatory disorders that may be associated with significant visual impairment. To our knowledge, few studies have investigated NIU prevalence overall or stratified by inflammation location, severity, presence of systemic conditions, age, or sex. OBJECTIVE: To estimate NIU prevalence using a large, retrospective, administrative claims database. DESIGN, SETTING, AND PARTICIPANTS: This analysis used the OptumHealth Reporting and Insights database to estimate 2012 NIU prevalence. Analysis was conducted in September 2016. The large administrative insurance claims database includes 14 million privately insured individuals in 69 self-insured companies spanning diverse industries. Included in the study were patients with NIU with 2 or more uveitis diagnoses on separate days in 2012 and continuous enrollment in a health plan for all of 2012 and categorized by inflammation site. MAIN OUTCOMES AND MEASURES: We estimated overall NIU prevalence by inflammation site, severity, sex, and age. Patients with anterior NIU were categorized by the presence of systemic conditions. RESULTS: Of the approximately 4 million eligible adult patients, approximately 2.1 million were women, and of the 932 260 children, 475 481 were boys. The adult prevalence of NIU was 121 cases per 100 000 persons (95% CI, 117.5-124.3). The pediatric NIU prevalence was 29 cases per 100 000 (95% CI, 26.1-33.2). Anterior NIU accounted for 81% (3904 cases) of adult NIU cases (98 per 100 000; 95% CI, 94.7-100.9) and 75% (207 cases) of pediatric NIU cases (22 per 100 000; 95% CI, 19.3-25.4). The prevalences of noninfectious intermediate, posterior, and panuveitis were, for adults, 1 (95% CI, 0.8-1.5), 10 (95% CI, 9.4-11.5), and 12 (95% CI, 10.6-12.7) per 100 000, respectively, and for pediatric patients, 0 (95% CI, 0.1-1.1), 3 (95% CI, 1.8-4.1), and 4 (95% CI, 2.9-5.6) per 100 000, respectively. The prevalence of NIU increased with age and was higher among adult females than males. Application of these estimates to the US population suggests that NIU affected approximately 298 801 American adults (95% CI, 290 512-307 324) and 21 879 children (95% CI, 19 360-24 626) in 2015. CONCLUSIONS AND RELEVANCE: The estimated prevalence of NIU was 121 cases per 100 000 for adults (95% CI, 117.5-124.3) and 29 per 100 000 for children (95% CI, 26.1-33.2). Prevalence was estimated using administrative claims from a commercially insured population, which may have a different prevalence than other segments of the US population. A better understanding of the prevalence of NIU will help to determine the number of patients affected.

Representation of Women With Industry Ties in Ophthalmology.

IMPORTANCE: Women in ophthalmology are growing in number and have made strides in traditional metrics of professional achievement. Professional ties to industry represent another potential means of career advancement, recognition, and income. OBJECTIVE: To report the representation of women among ophthalmologists receiving industry remuneration for research, consulting, honoraria, grants, royalties, and faculty/speaker roles. DESIGN, SETTING, AND PARTICIPANTS: In this observational, retrospective study, the Centers for Medicare and Medicaid Services Open Payments database for payments to ophthalmologists by biomedical companies was reviewed for representation, median payments, and mean payments by women and men for industry relationships in 2013 and 2014. The analysis was performed from July 2015 to November 2015. MAIN OUTCOMES AND MEASURES: The primary outcome measures were percentage representation of women vs men overall and in industry research, consulting, speaking roles, royalties and licenses, grants, services other than consulting, and honoraria. Secondary outcome measures included mean and median payments from industry to female vs male ophthalmologists. RESULTS: In 2013, 4164 of 21 380 (19.5%) ophthalmologists were women, and of 1204 ophthalmologists analyzed for industry payments, 176 (4.2%) women had industry ties compared with 1028 (6%) men (P < .001). Mean payments to women were $11 419 compared with $20 957 for men (P = .001), and median payments to women were $3000 compared with $4787 for men (P = .007). In 2013, women were underrepresented among ophthalmologists receiving industry payments for research (49 of 462 [10.6%]), consulting (96 of 610 [15.7%]), honoraria (3 of 47 [6.4%]), industry grants (1 of 7 [14.3%]), royalties and licenses (1 of 13 [7.7%]), and faculty/speaker roles (2 of 48 [4.2%]). In 2014, 4352 of 21 531 (20.2%) of ophthalmologists were women. Of 1518 ophthalmologists analyzed for industry payments, 255 (6%) women had industry ties compared with 1263 (7.4%) men (P < .001). Mean payments to women were $14 848 compared with $30 513 for men (P = .004), and median payments to women were $3750 compared with $5000 for men (P = .005). Women remained underrepresented among ophthalmologists receiving industry payments for research (25 of 241 [10.4%]), consulting (145 of 921 [15.7%]), honoraria (14 of 11 [12.6%]), industry grants (3 of 25 [12.0%]), royalties and licenses (1 of 22 [4.6%]), and faculty/speaker roles (21 of 189 [11.1%]) in 2014. CONCLUSIONS AND RELEVANCE: Women make up a minority of ophthalmologists with professional industry relationships, and the average woman partnering with industry earns less than her male colleagues. The reasons for differences are multifactorial and could not be determined by this study.

A picture is worth a thousand words: maps of HIV indicators to inform research, programs, and policy from NA-ACCORD and CCASAnet clinical cohorts.

INTRODUCTION: Maps are powerful tools for visualization of differences in health indicators by geographical region, but multi-country maps of HIV indicators do not exist, perhaps due to lack of consistent data across countries. Our objective was to create maps of four HIV indicators in North, Central, and South American countries. METHODS: Using data from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) and the Caribbean, Central, and South America network for HIV epidemiology (CCASAnet), we mapped median CD4 at presentation for HIV clinical care, proportion retained in HIV primary care, proportion prescribed antiretroviral therapy (ART), and the proportion with suppressed plasma HIV viral load (VL) from 2010 to 2012 for North, Central, and South America. The 15 Canadian and US clinical cohorts and 7 clinical cohorts in Argentina, Brazil, Chile, Haiti, Honduras, Mexico, and Peru represented approximately 2-7% of persons known to be living with HIV in these countries. RESULTS: Study populations were selected for each indicator: median CD4 at presentation for care was estimated among 14,811 adults; retention was estimated among 87,979 adults; ART use was estimated among 84,757 adults; and suppressed VL was estimated among 51,118 adults. Only three US states and the District of Columbia had a median CD4 at presentation >350 cells/mm(3). Haiti, Mexico, and several states had >85% retention in care; lower (50-74%) retention in care was observed in the US West, South, and Mid-Atlantic, and in Argentina, Brazil, and Peru. ART use was highest (90%) in Mexico. The percentages of patients with suppressed VL in the US South and Northeast were lower than in most of Central and South America. CONCLUSIONS: These maps provide visualization of gaps in the quality of HIV care and allow for comparison between and within countries as well as monitoring policy and programme goals within geographical boundaries.

Direct and indirect resource use, healthcare costs and work force absence in patients with non-infectious intermediate, posterior or panuveitis.

PURPOSE: To ascertain resource use, costs and risk of workforce absence in non-infectious uveitis cases versus matched controls. METHODS: In a retrospective claims analysis of employees in the United States, prevalent (N = 705) and incident (N = 776) cases 18-64 years old with ≥2 diagnoses of non-infectious intermediate, posterior or panuveitis were matched 1:1 to controls without uveitis. Persistent prevalent cases (treated for ≥90 days, N = 112) also were analysed. Outcomes were annual direct resource use and costs associated with inpatient stays; emergency department, outpatient and ophthalmologist/optometrist visits; and prescription drugs. Indirect resource use and costs associated with work loss from disability and medically related absenteeism also were compared. Multivariate regression assessed cost differences between cases and controls. RESULTS: Cases had significantly (p < 0.05) more medical resource use versus controls including 0.4 versus 0.2 emergency visits and 16.5 versus 7.6 outpatient/other visits. Cases used more prescription drugs (7.8 versus 4.1) and had more disability days (10.3 versus 4.6), medically related absenteeism days (8.5 versus 3.8), and work loss days (18.7 versus 8.4) than controls (all p < 0.05). Total direct ($12 940 versus $3730) and indirect ($3144 versus $1378) costs were higher in cases than controls (all p < 0.05). Results for persistent cases suggested greater utilization and associated cost and work loss burden. Compared with controls, cases had significantly greater risks of workforce absence, leave of absence and long-term disability (all p < 0.05). CONCLUSION: Non-infectious intermediate, posterior or panuveitis, particularly persistent disease, is associated with substantial medical and work loss costs suggesting an unmet need for more effective treatments.

Using a patient-centered approach to benefit-harm assessment in treatment decision-making: a case study in uveitis.

BACKGROUND: Synthesizing evidence from comparative effectiveness trials can be difficult because multiple outcomes of different importance are to be considered. The goal of this study was to demonstrate an approach to conducting quantitative benefit-harm assessment that considers patient preferences. METHODS: We conducted a benefit-harm assessment using data from the Multicenter Uveitis Steroid Treatment Trial that compared corticosteroid implant versus systemic corticosteroids and immunosuppression in non-infectious intermediate, posterior, and panuveitis. We focused on clinical outcomes considered important to patients, including visual acuity, development of cataracts/glaucoma, need for eye surgery, prescription-requiring hypertension, hyperlipidemia, and infections. Patient preferences elicited in a recent survey were then incorporated into our assessment of the benefit-harm balance. RESULTS: Benefit-harm metrics were calculated for each time point that summarized the numbers of outcomes, caused or prevented by implant therapy versus systemic therapy if 1000 patients were treated. The benefit-harm metric was -129 (95% confidence interval: -242 to -14), -317 (-436 to -196), -390 (-514 to -264), and -526 (-687 to -368) at 6, 12, 18, and 24 months follow up, respectively, suggesting that systemic therapy may have a better benefit-harm balance. However, measures of quality of life for patients treated with implant therapy were found to be better than patients treated with systemic therapy over the same time period. CONCLUSIONS: Results of benefit-harm assessment were different from the prospectively collected quality of life data during trial follow up. Future studies should explore the reasons for such discrepancies and the strength and weakness of each method to assess treatment benefits and harms.

Topical Nonsteroidal Anti-inflammatory Drugs and Cataract Surgery: A Report by the American Academy of Ophthalmology.

OBJECTIVE: To review the available evidence on the effectiveness of prophylactic topical nonsteroidal anti-inflammatory drugs (NSAIDs) in preventing vision loss resulting from cystoid macular edema (CME) after cataract surgery. METHODS: Literature searches of the PubMed and the Cochrane Library databases were last conducted on January 21, 2015, with no date restrictions. The searches retrieved 149 unique citations. The first author reviewed the abstracts of these articles and selected 27 articles of possible clinical relevance for full-text review. Of these 27 articles, 12 were deemed relevant to analyze in full. Two additional articles were identified from the reference list of the selected articles, and another article was identified from a national meeting. The panel methodologist assigned ratings of level of evidence to each of the selected citations. RESULTS: Nonsteroidal anti-inflammatory drug therapy was effective in reducing CME detected by angiography or optical coherence tomography (OCT) and may increase the speed of visual recovery after surgery when compared directly with placebo or topical corticosteroid formulations with limited intraocular penetration. However, the use of NSAIDs did not alter long-term (≥3 months) visual outcomes. Furthermore, there was no evidence that the benefits observed with NSAID therapy could not be obtained similarly with equivalent dosing of a corticosteroid. The reported impression that there is a pharmacologic drug synergy from the use of both an NSAID and a corticosteroid is not supported by the literature. There is no uniform method of reporting CME in the literature, which prevents accurate assessment of its incidence and response to anti-inflammatory therapies. CONCLUSIONS: Cystoid macular edema after cataract surgery has a tendency to resolve spontaneously. There is a lack of level I evidence that supports the long-term benefit of NSAID therapy to prevent vision loss from CME at 3 months or more after cataract surgery. Although dosing of NSAIDs before surgery may hasten the speed of visual recovery in the first several weeks after cataract surgery, there is no evidence that this practice affects long-term visual outcomes. Standardized reporting of CME based on OCT may allow for more uniform quantitation of its incidence and more reliable assessment of treatment outcomes.

Therapies for macular edema associated with central retinal vein occlusion: a report by the American Academy of Ophthalmology.

PURPOSE: To review the available evidence regarding the safety and efficacy of therapies for the treatment of macular edema (ME) associated with central retinal vein occlusion (CRVO). METHODS: A literature search of the PubMed database was last conducted in March 2014 with no date restrictions but limited to articles published in English. A literature search of the Cochrane Library was also conducted in March 2014 with no date restrictions and without a language limitation. The combined searches yielded 108 citations, of which 20 were deemed clinically relevant for the Ophthalmic Technology Assessment Committee Retina/Vitreous panel to review in full text. Three additional studies were also identified for panel review. The level of evidence of these selected studies was reviewed by the panel methodologist. RESULTS: There were 7 citations representing 4 clinical trials that provided level I evidence supporting the use of anti-vascular endothelial growth factor (VEGF) pharmacotherapies for ME associated with CRVO, including intravitreal ranibizumab (2), aflibercept (3), and bevacizumab (2). There were 3 citations representing 2 studies with level I evidence for intravitreal corticosteroid injection with dexamethasone intravitreal implant (2 citations) or triamcinolone (1 citation), although cataract and glaucoma were observed in these studies. Level I evidence is available on the limited benefit of macular grid-pattern laser photocoagulation (1 citation). Eight other citations reviewed were rated as level II, and 4 citations were rated as level III. Long-term efficacy results (≥2 years of follow-up) are limited to intravitreal ranibizumab at this time, and few studies have evaluated combination therapy with anti-VEGF and corticosteroid versus monotherapy of either class of drug. CONCLUSIONS: Level I evidence indicates that intravitreal anti-VEGF pharmacotherapy is safe and effective over 2 years for ME associated with CRVO and that delay in treatment is associated with worse visual outcomes. In addition, level I evidence demonstrates short-term efficacy of intravitreal corticosteroid but also an association with a higher frequency of adverse events.

Cost-effectiveness of fluocinolone acetonide implant versus systemic therapy for noninfectious intermediate, posterior, and panuveitis.

OBJECTIVE: To evaluate the 3-year incremental cost-effectiveness of fluocinolone acetonide implant versus systemic therapy for the treatment of noninfectious intermediate, posterior, and panuveitis. DESIGN: Randomized, controlled, clinical trial. PARTICIPANTS: Patients with active or recently active intermediate, posterior, or panuveitis enrolled in the Multicenter Uveitis Steroid Treatment Trial. METHODS: Data on cost and health utility during 3 years after randomization were evaluated at 6-month intervals. Analyses were stratified by disease laterality at randomization (31 unilateral vs 224 bilateral) because of the large upfront cost of the implant. MAIN OUTCOME MEASURES: The primary outcome was the incremental cost-effectiveness ratio (ICER) over 3 years: the ratio of the difference in cost (in United States dollars) to the difference in quality-adjusted life-years (QALYs). Costs of medications, surgeries, hospitalizations, and regular procedures (e.g., laboratory monitoring for systemic therapy) were included. We computed QALYs as a weighted average of EQ-5D scores over 3 years of follow-up. RESULTS: The ICER at 3 years was $297,800/QALY for bilateral disease, driven by the high cost of implant therapy (difference implant - systemic [Δ]: $16,900; P < 0.001) and the modest gains in QALYs (Δ = 0.057; P = 0.22). The probability of the ICER being cost-effective at thresholds of $50,000/QALY and $100,000/QALY was 0.003 and 0.04, respectively. The ICER for unilateral disease was more favorable, namely, $41,200/QALY at 3 years, because of a smaller difference in cost between the 2 therapies (Δ = $5300; P = 0.44) and a larger benefit in QALYs with the implant (Δ = 0.130; P = 0.12). The probability of the ICER being cost-effective at thresholds of $50,000/QALY and $100,000/QALY was 0.53 and 0.74, respectively. CONCLUSIONS: Fluocinolone acetonide implant therapy was reasonably cost-effective compared with systemic therapy for individuals with unilateral intermediate, posterior, or panuveitis but not for those with bilateral disease. These results do not apply to the use of implant therapy when systemic therapy has failed or is contraindicated. Should the duration of implant effect prove to be substantially >3 years or should large changes in therapy pricing occur, the cost-effectiveness of implant versus systemic therapy would need to be reevaluated.

Association between U.S. state AIDS Drug Assistance Program (ADAP) features and HIV antiretroviral therapy initiation, 2001-2009.

BACKGROUND: U.S. state AIDS Drug Assistance Programs (ADAPs) are federally funded to provide antiretroviral therapy (ART) as the payer of last resort to eligible persons with HIV infection. States differ regarding their financial contributions to and ways of implementing these programs, and it remains unclear how this interstate variability affects HIV treatment outcomes. METHODS: We analyzed data from HIV-infected individuals who were clinically-eligible for ART between 2001 and 2009 (i.e., a first reported CD4+ <350 cells/uL or AIDS-defining illness) from 14 U.S. cohorts of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). Using propensity score matching and Cox regression, we assessed ART initiation (within 6 months following eligibility) and virologic suppression (within 1 year) based on differences in two state ADAP features: the amount of state funding in annual ADAP budgets and the implementation of waiting lists. We performed an a priori subgroup analysis in persons with a history of injection drug use (IDU). RESULTS: Among 8,874 persons, 56% initiated ART within six months following eligibility. Persons living in states with no additional state contribution to the ADAP budget initiated ART on a less timely basis (hazard ratio [HR] 0.73, 95% CI 0.60-0.88). Living in a state with an ADAP waiting list was not associated with less timely initiation (HR 1.12, 95% CI 0.87-1.45). Neither additional state contributions nor waiting lists were significantly associated with virologic suppression. Persons with an IDU history initiated ART on a less timely basis (HR 0.67, 95% CI 0.47-0.95). CONCLUSIONS: We found that living in states that did not contribute additionally to the ADAP budget was associated with delayed ART initiation when treatment was clinically indicated. Given the changing healthcare environment, continued assessment of the role of ADAPs and their features that facilitate prompt treatment is needed.

U.S. trends in antiretroviral therapy use, HIV RNA plasma viral loads, and CD4 T-lymphocyte cell counts among HIV-infected persons, 2000 to 2008.

BACKGROUND: The U.S. National HIV/AIDS Strategy targets for 2015 include "increasing access to care and improving health outcomes for persons living with HIV in the United States" (PLWH-US). OBJECTIVE: To demonstrate the utility of the NA-ACCORD (North American AIDS Cohort Collaboration on Research and Design) for monitoring trends in the HIV epidemic in the United States and to present trends in HIV treatment and related health outcomes. DESIGN: Trends from annual cross-sectional analyses comparing patients from pooled, multicenter, prospective, clinical HIV cohort studies with PLWH-US, as reported to national surveillance systems in 40 states. SETTING: U.S. HIV outpatient clinics. PATIENTS: HIV-infected adults with 1 or more HIV RNA plasma viral load (HIV VL) or CD4 T-lymphocyte (CD4) cell count measured in any calendar year from 1 January 2000 to 31 December 2008. MEASUREMENTS: Annual rates of antiretroviral therapy use, HIV VL, and CD4 cell count at death. RESULTS: 45 529 HIV-infected persons received care in an NA-ACCORD-participating U.S. clinical cohort from 2000 to 2008. In 2008, the 26 030 NA-ACCORD participants in care and the 655 966 PLWH-US had qualitatively similar demographic characteristics. From 2000 to 2008, the proportion of participants prescribed highly active antiretroviral therapy increased by 9 percentage points to 83% (P < 0.001), whereas the proportion with suppressed HIV VL (≤2.7 log10 copies/mL) increased by 26 percentage points to 72% (P < 0.001). Median CD4 cell count at death more than tripled to 0.209 × 109 cells/L (P < 0.001). LIMITATION: The usual limitations of observational data apply. CONCLUSION: The NA-ACCORD is the largest cohort of HIV-infected adults in clinical care in the United States that is demographically similar to PLWH-US in 2008. From 2000 to 2008, increases were observed in the percentage of prescribed HAART, the percentage who achieved a suppressed HIV VL, and the median CD4 cell count at death. PRIMARY FUNDING SOURCE: National Institutes of Health; Centers for Disease Control and Prevention; Canadian Institutes of Health Research; Canadian HIV Trials Network; and the government of British Columbia, Canada.

Long-term risk of malignancy among patients treated with immunosuppressive agents for ocular inflammation: a critical assessment of the evidence.

PURPOSE: To critically assess potentially carcinogenic effects of immunosuppressive therapy in the ocular inflammation setting. DESIGN: Focused evidence assessment. METHODS: Relevant publications were identified by MEDLINE and EMBASE queries and reference list searches. RESULTS: Extrapolation from transplant, rheumatology, skin disease, and inflammatory bowel disease cohorts to the ocular inflammation setting suggest that: 1) alkylating agents increase hematologic malignancy risk and cyclophosphamide increases bladder cancer risk, but less so with < or =18 months' duration of therapy and hydration, respectively; 2) calcineurin inhibitors and azathioprine probably do not increase total cancer risk to a detectable degree, except perhaps some other risk factors (uncommon in ocular inflammation patients) might interact with the former to raise risk; 3) tumor necrosis factor (TNF) inhibitors may accelerate diagnosis of cancer in the first six to 12 months, but probably do not increase long-term cancer risk; and 4) changes in risk with methotrexate, mycophenolate mofetil, and daclizumab appear negligible, although nontransplant data are limited for the latter agents. Immunosuppression in general may increase skin cancer risk in a sun exposure-dependent manner. CONCLUSION: Use of alkylating agents for a limited duration seems justifiable for severe, vision-threatening disease, but otherwise cancer risk may be a relevant constraint on use of this approach. Antimetabolites, daclizumab, TNF inhibitors, and calcineurin inhibitors probably do not increase cancer risk to a degree that outweighs the expected benefits of therapy. Monitoring for skin cancer may be useful for highly sun-exposed patients. Data from ocular inflammation patients are needed to confirm the conclusions made in this analysis by extrapolation.