Anti-Vascular Endothelial Growth Factor Drugs Compared With Panretinal Photocoagulation for the Treatment of Proliferative Diabetic Retinopathy: A Cost-Effectiveness Analysis.

OBJECTIVES: This study aimed to evaluate the cost-effectiveness of anti-vascular endothelial growth factor drugs (anti-VEGFs) compared with panretinal photocoagulation (PRP) for treating proliferative diabetic retinopathy (PDR) in the United Kingdom. METHODS: A discrete event simulation model was developed, informed by individual participant data meta-analysis. The model captures treatment effects on best corrected visual acuity in both eyes, and the occurrence of diabetic macular edema and vitreous hemorrhage. The model also estimates the value of undertaking further research to resolve decision uncertainty. RESULTS: Anti-VEGFs are unlikely to generate clinically meaningful benefits over PRP. The model predicted anti-VEGFs be more costly and similarly effective as PRP, generating 0.029 fewer quality-adjusted life-years at an additional cost of £3688, with a net health benefit of -0.214 at a £20 000 willingness-to-pay threshold. Scenario analysis results suggest that only under very select conditions may anti-VEGFs offer potential for cost-effective treatment of PDR. The consequences of loss to follow-up were an important driver of model outcomes. CONCLUSIONS: Anti-VEGFs are unlikely to be a cost-effective treatment for early PDR compared with PRP. Anti-VEGFs are generally associated with higher costs and similar health outcomes across various scenarios. Although anti-VEGFs were associated with lower diabetic macular edema rates, the number of cases avoided is insufficient to offset the additional treatment costs. Key uncertainties relate to the long-term comparative effectiveness of anti-VEGFs, particularly considering the real-world rates and consequences of treatment nonadherence. Further research on long-term visual acuity and rates of vision-threatening complications may be beneficial in resolving uncertainties.

The estimated healthcare cost of diabetic retinopathy in Indonesia and its projection for 2025.

PURPOSE: To estimate the total healthcare cost associated with diabetic retinopathy (DR) in type 2 diabetes in Indonesia and its projection for 2025. METHODS: A prevalence-based cost-of-illness model was constructed from previous population-based DR study. Projection for 2025 was derived from estimated diabetes population in 2025. Direct treatment costs of DR were estimated from the perspective of healthcare. Patient perspective costs were obtained from thorough interview including only transportation cost and lost of working days related to treatment. We developed four cost-of-illness models according to DR severity level, DR without necessary treatment, needing laser treatment, laser +intravitreal (IVT) injection and laser + IVT +vitrectomy. All costs were estimated in 2017 US$. RESULTS: The healthcare costs of DR in Indonesia were estimated to be $2.4 billion in 2017 and $8.9 billion in 2025. The total cost in 2017 consisted of the cost for no DR and mild-moderate non-proliferative DR (NPDR) requiring eye screening ($25.9 million), severe NPDR or proliferative DR (PDR) requiring laser treatment ($0.25 billion), severe NPDR or PDR requiring both laser and IVT injection ($1.75 billion) and advance level of PDR requiring vitrectomy ($0.44 billion). CONCLUSIONS: The estimated healthcare cost of DR in Indonesia in 2017 was considerably high, nearly 2% of the 2017 national state budget, and projected to increase significantly to more than threefold in 2025. The highest cost may incur for DR requiring both laser and IVT injection. Therefore, public health intervention to delay or prevent severe DR may substantially reduce the healthcare cost of DR in Indonesia.

Five-Year Cost-effectiveness of Intravitreous Ranibizumab Therapy vs Panretinal Photocoagulation for Treating Proliferative Diabetic Retinopathy: A Secondary Analysis of a Randomized Clinical Trial.

Importance: The DRCR Retina Network Protocol S randomized clinical trial suggested that the mean visual acuity of eyes with proliferative diabetic retinopathy (PDR) treated with ranibizumab is not worse at 5 years than that of eyes treated with panretinal photocoagulation (PRP). Moreover, the ranibizumab group had fewer new cases of diabetic macular edema (DME) with vision loss or vitrectomy but had 4 times the number of injections and 3 times the number of visits. Although 2-year cost-effectiveness results of Protocol S were previously identified, incorporating 5-year data from Protocol S could alter the longer-term cost-effectiveness of the treatment strategies from the perspective of the health care system. Objective: To evaluate 5- and 10-year cost-effectiveness of therapy with ranibizumab, 0.5 mg, compared with PRP for treating PDR. Design, Setting, and Participants: A preplanned secondary analysis of the Protocol S randomized clinical trial using efficacy, safety, and resource utilization data through 5 years of follow-up for 213 adults diagnosed with PDR and simulating results through 10 years. Interventions: Intravitreous ranibizumab, 0.5 mg, at baseline and as frequently as every 4 weeks based on a structured retreatment protocol vs PRP at baseline for PDR; eyes in both groups could receive ranibizumab for concomitant DME with vision loss. Main Outcomes and Measures: Incremental cost-effectiveness ratios (ICERs) of ranibizumab therapy compared with PRP were evaluated for those with and without center-involved DME (CI-DME) and vision loss (Snellen equivalent, 20/32 or worse) at baseline. Results: The study included 213 adults with a mean (SD) age of 53 (12) years, of whom 92 (43%) were women and 155 (73%) were white. The ICER of the ranibizumab group compared with PRP for patients without CI-DME at baseline was $582 268 per quality-adjusted life-year (QALY) at 5 years and $742 202/QALY at 10 years. For patients with baseline CI-DME, ICERs were $65 576/QALY at 5 years and $63 930/QALY at 10 years. Conclusions and Relevance: This study suggests that during 5 to 10 years of treatment, ranibizumab, 0.5 mg, as given in the studied trial compared with PRP may be within the frequently cited range considered cost-effective in the United States for eyes presenting with PDR and vision-impairing CI-DME, but not for those with PDR but without vision-impairing CI-DME. Substantial reductions in anti-vascular endothelial growth factor cost may make the ranibizumab therapy cost-effective within this range even for patients without baseline CI-DME. Trial Registration: ClinicalTrials.gov identifier: NCT01489189.

A Worldwide Price Comparison of Glaucoma Medications, Laser Trabeculoplasty, and Trabeculectomy Surgery.

Importance: Medical and surgical interventions for glaucoma are effective only if they are affordable to patients. Little is known about how affordable glaucoma interventions are in developing and developed countries. Objective: To compare the prices of topical glaucoma medications, laser trabeculoplasty, and trabeculectomy relative with median annual household income (MA-HHI) for countries worldwide. Design, Setting and Participants: Cross-sectional observational study. For each country, we obtained prices for glaucoma medications, laser trabeculoplasty, and trabeculectomy using government pricing data, drug databases, physician fee schedules, academic publications, and communications with local ophthalmologists. Prices were adjusted for purchasing power parity and inflation to 2016 US dollars, and annual therapy prices were examined relative to the MA-HHI. Interventions costing less than 2.5% of the MA-HHI were considered affordable. Main Outcomes and Measures: Daily cost for topical glaucoma medications, cost of annual therapy with glaucoma medications, laser trabeculoplasty, and trabeculectomy relative to MA-HHI in each country. Results: Data were obtained from 38 countries, including 17 developed countries and 21 developing countries, as classified by the World Economic Outlook. We observed considerable variability in intervention prices compared with MA-HHI across the countries and across interventions, ranging from 0.1% to 5% of MA-HHI for timolol, 0.1% to 27% for latanoprost, 0.2% to 17% for laser trabeculoplasty, and 0.3% to 42% for trabeculectomy. Timolol was the most affordable medication in all countries studied and was 2.5% or more of MA-HHI in only 2 countries (5%). The annual cost of latanoprost was 2.5% or more of MA-HHI in 15 countries (41%) (15 developing countries [75%] and no developed countries). The cost of laser trabeculoplasty was 2.5% or more of the MA-HHI in 15 countries (44%) (11 developing countries [65%] and 4 developed countries [24%]). The cost of trabeculectomy was 2.5% or more of the MA-HHI in 28 countries (78%) (18 developing countries [95%] and 10 developed countries [59%]). In 18 countries (53%), laser trabeculoplasty cost less than a 3-year latanoprost supply. Conclusions and Relevance: For many patients worldwide, the costs of medical, laser, and incisional surgical interventions were 2.5% or more of the MA-HHI. Successfully reducing global blindness from glaucoma requires addressing multiple contributing factors, including making glaucoma interventions more affordable.

Cost Evaluation of Early Vitrectomy versus Panretinal Photocoagulation and Intravitreal Ranibizumab for Proliferative Diabetic Retinopathy.

PURPOSE: To evaluate costs and cost-utility of early vitrectomy (pars plana vitrectomy [PPV]) compared with panretinal photocoagulation (PRP) and intravitreal ranibizumab (IVR) for proliferative diabetic retinopathy (PDR) without diabetic macular edema. DESIGN: A decision analysis model of cost-utility. PARTICIPANTS: There were no participants. METHODS: A decision analysis was based on results from the Diabetic Retinopathy Clinical Research Network Protocol S comparing treatment of PRP with IVR (0.3 mg) in PDR without incident macular edema to model the total 2-year costs and outcomes for each treatment scenario. These values were compared with the 2-year hypothetical costs of early PPV for PDR. Centers for Medicare and Medicaid Services data were used to calculate associated modeled costs in a hospital/facility-based and nonfacility setting. Cost-utility was calculated on the basis of the preserved visual utility and estimated life years remaining. In addition, costs for lifetime treatment were modeled for all scenarios and used to calculate lifetime quality-adjusted life years (QALY) costs for each scenario. Sensitivity analyses were performed to evaluate the impact of the model's assumptions. MAIN OUTCOME MEASURES: Cost of treatment, utility, and cost per QALY. RESULTS: The modeled cost per QALY of treatment for PDR for 2 years of utility in the facility (nonfacility) setting was $163 988 ($102 559) in the PRP group, $436 992 ($326 424) in the IVR group, and $181 144 ($107 965) in the PPV group. Sensitivity analysis showed that both IVR and PPV groups would have equivalent costs per QALY over the first 2 years if 78% (facility) and 80% (nonfacility) of patients in the PPV group required additional treatment with IVR (at the dose of 10.1 injections as in Protocol S). Beyond 2 years, the cost per QALY in the facility (nonfacility) setting was calculated as $61 695 ($21 752) in the PRP group, $338 348 ($239 741) in the IVR group, and $63 942 ($22 261) in the PPV group. CONCLUSIONS: Early PPV as a strategy for treatment of PDR without macular edema demonstrates cost-utility similar to management with PRP and more favorable cost-utility compared with IVR in the short term. This advantage over IVR continues when lifetime costs are factored.

GreenLight Laser for benign prostatic hyperplasia.

PURPOSE OF REVIEW: GreenLight photoselective vaporization (GL-PV) is now established in the treatment of benign prostatic enlargement. The present review outlines the available technical armamentarium and summarizes the current best evidence on functional and safety outcomes. Moreover, future technical developments and refinements are presented. RECENT FINDINGS: GL-PV has evolved to be the most commonly performed procedure, second to conventional transurethral resection of the prostate (TURP) for surgical management of benign prostatic obstruction (BPO). On the basis of the data published in the randomized controlled Goliath study, GL-PV with 180-W technology is noninferior in terms of functional outcomes compared with TURP considering short and intermediate follow-up with a complication-free rate of around 80% after 24 months.The ongoing push towards high-power lasers can be explained by their more effective tissue ablative effect, leading to shorter operating times. Comparative analysis between high-power and low-power laser systems demonstrated similar retreatment rates and most institutions are, therefore, now performing 180-W GL-PV.Performed as an outpatient procedure, GL-PV is cost-effective with a low hospital re-admission rate. Plasma kinetic vaporization of the prostate (PKVP) has recently emerged as a potential contender in the field; also GreenLight enucleation of the prostate (GreenLEP) might be even more effective than GL-PV. SUMMARY: GL-PV appears to be a well tolerated surgical alternative for patients suffering from BPO. Long-term follow-up data from 120-W and 180-W laser systems are still pending. Potential competitors have recently been brought to the market and further trials and long-term data will show, whether GL-PV will stand the test of time. Regardless of technical specifications, surgeon's experience remains essential to achieve good functional and safety outcomes.

[What is the cost of treatment of diabetic retinopathy by argon laser in Yaoundé?] / Quel coût pour le traitement de la rétinopathie diabétique par laser argon à Yaoundé ?

PURPOSE: To evaluate the total cost of treatment of diabetic retinopathy by argon laser for a patient when indicated. PATIENTS AND METHOD: Prospective cross-sectional and descriptive survey, carried out in the angiography and laser center of the Yaoundé Central Hospital from October 2014 to October 2015. All consecutive diabetic patients with retinopathy and suitable indication for argon laser treatment were included. The costs related to the initial and final fluorescein angiography, the appointment for follow-up, round-trip transportation costs from the patient's home and the cost of laser treatment were included. RESULTS: Included were 43 (13 %) patients out of 330 with diabetic retinopathy. The mean age was 55.67±8.40years. There were 25 women (58.1 %) and 18 men (41.9 %) for a M/F ratio of 0.7. Unemployed patients were represented by 28 (65.1 %) versus 15 employed (34.9 %). Twenty-seven patients (62.8 %) were self-pay for all their expenses, 14 (32.6 %) were assisted by their families, and 2 (4.6 %) were insured. On average, the total expenditure was 86002±67197 f CFA per eye, corresponding to 131±102 euros with an exchange rate of 1 euro for 656 f CFA. CONCLUSION: The cost of treatment of diabetic retinopathy by argon laser is high, mostly increased by the additional costs related to transportation in our area. The creation of satellite centers in the 10 regions of Cameroon would reduce these costs.

Accuracy of Billing Codes Used in the Therapeutic Care of Diabetic Retinopathy.

Importance: Insurance billing claim databases represent a growing field of scientific inquiry within ophthalmology. Validating the accuracy of billing claim codes used during the care of diabetic retinopathy is a necessary precursor to fully understanding the underlying data and subsequent results of these types of studies. Objective: To determine the accuracy of diagnostic, procedural, and therapeutic billing codes used in the treatment of diabetic retinopathy. Design, Setting, and Participants: This retrospective medical record review was conducted at 3 clinical practices (1 academic and 2 private). Insured patients with diabetic retinopathy were seen by the practices between 2011 and 2013. Each patient then had every visit for 2 years reviewed twice, once for billing data and the second for data from the medical record. Data were collected and analyzed from October 2015 to July 2016. Main Outcomes and Measures: The positive predictive value (PPV) and negative predictive value (NPV) for each code of interest. Sensitivity and specificity were secondary outcomes. Results: A total of 146 patients (mean [SD] age, 60.3 [12.5] years) from 11 physicians had 1072 encounters reviewed over 2 calendar years. Among the included patients, 49.3% were female (n = 72), 48.6% were white (n = 71), 37.0% were black (n = 54), and 18.5% had type 1 diabetes and a mean (SD) hemoglobin A1C level of 7.7% (1.8) (n = 27). Nearly all codes of interest that were used frequently also had a high PPV (range, 89.5%-100%) and NPV (88.6%-100%) including billing codes for intravitreal injection, focal laser, panretinal photocoagulation, laterality of procedure, ranibizumab, bevacizumab, fundus photographs, fluorescein angiography, and optical coherence tomography. Codes that were used infrequently (<20 instances) but still had a high PPV (all 100%) and NPV (99.7%-100%) were codes for aflibercept, triamcinolone, and the dexamethasone implant. Only the codes for infrequently used B-scan ultrasonography (PPV, 69.6%) and subtenon injection (PPV, 100%; NPV, 99.7%, but sensitivity of only 40%) were found to be of questionable accuracy. Other than subtenon injection (40%), all codes were also found to have a high sensitivity (range, 87.6%-100%) and a high specificity (range, 97.2%-100%). Conclusions and Relevance: These data suggest diagnostic, procedure, and therapeutic codes derived from insurance billing claims accurately reflect the medical record for patients with diabetic retinopathy.

Cost-effectiveness of Intravitreous Ranibizumab Compared With Panretinal Photocoagulation for Proliferative Diabetic Retinopathy: Secondary Analysis From a Diabetic Retinopathy Clinical Research Network Randomized Clinical Trial.

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.

[Economic aspects of diabetic macular edema treatment at regional level in Russian Federation]. / Ékonomicheskie aspekty lecheniia diabeticheskogo makuliarnogo oteka na regional'nom urovne v Rossiiskoi Federatsii.

An assessment of economic burden of Diabetic Macular Edema (DME) in Russian Federation was conducted on the example of four pilot regions including Samara Region, Republic of Bashkortostan, Chuvash Republic and Yaroslavl Region. The assessment involved a newly developed interactive pharmacoeconomic model that uses data from questionnaire surveys of leading DME experts residing in the regions. In the course of the study, direct and indirect costs associated with DME were calculated. The highest direct costs of DME treatment were seen in the Republic of Bashkortostan - 302 482 RUB/year per patient. Direct cost of treating a single DME patient in the Samara Region was 34 271 RUB/year, in the Yaroslavl Region - 32 308 RUB/year and in the Chuvash Republic - 12 243 RUB/year. Indirect costs per DME patient in the Samara Region amounted to 67 530 RUB/year, in the Yaroslavl Region - 75 177 RUB/year, in the Republic of Bashkortostan - 102 884 RUB/year and in the Chuvash Republic - 81 082 RUB/year. Total annual costs per DME patient in the Samara Region was 101 801 RUB/year, in the Yaroslavl Region - 107 485 RUB/year, in the Republic of Bashkortostan - 405 366 RUB/year and in the Chuvash Republic - 93 325 RUB/year.

Cost Evaluation of Panretinal Photocoagulation versus Intravitreal Ranibizumab for Proliferative Diabetic Retinopathy.

PURPOSE: To evaluate costs of panretinal photocoagulation (PRP) vs. intravitreal ranibizumab (IVR) for proliferative diabetic retinopathy (PDR). DESIGN: A Markov-style model of cost-effectiveness and cost utility. PARTICIPANTS: There were no participants. METHODS: Based on results from Diabetic Retinopathy Clinical Research (DRCR) Network Protocol S, we performed a Markov-style analysis to generate the total 2-year costs for each treatment arm. The cost per line-year saved and cost utility were calculated based on the estimated life years remaining. Both treatment arms were assumed to result in 9 lines of vision saved in 20% of patients. Medicare reimbursement data were acquired to determine costs, which were then separately calculated for practice settings of a hospital-based facility as the highest end of the cost range and a nonfacility in the same geographic area as the lowest end. Cost parameters for a prototypical patient's life expectancy also were modeled and calculated. MAIN OUTCOME MEASURES: Inputed cost of therapy, cost per line saved, cost per line-year saved, and cost per quality-adjusted life years (QALY). RESULTS: When PRP was the primary treatment, the 2-year cost in the facility setting was $13 053, with cost per line saved $7252, cost per line-year $240, and cost per QALY $7988. In the nonfacility setting costs were approximately 21% lower. When IVR was the primary treatment, the 2-year cost in the facility setting was $30 328, cost per line saved was $16 849, cost per line-year $575, and cost per QALY $19 150. In the nonfacility setting costs were approximately 15% lower. Extrapolation to lifetime therapy yielded the cost per QALY with PRP treatment of $14 219 to $24 005 and with IVR of $138 852 to $164 360. Cost utility for PRP would be 85% lower than IVR in the facility setting and 90% lower than IVR in the nonfacility setting. CONCLUSIONS: PRP compared with IVR as primary treatment for PDR is less expensive over 2 years, but both fall well below the accepted cost per QALY upper limit. However, over an average lifetime, the cost differential between PRP and IVR increases, and IVR therapy may exceed the typical accepted limit of cost per QALY.

Cost-effectiveness of ranibizumab in the treatment of visual impairment due to diabetic macular edema.

Objective Ranibizumab, an anti-vascular endothelial growth factor designed for ocular use, has been deemed cost-effective in multiple indications by several Health Technology Assessment bodies. This study assessed the cost-effectiveness of ranibizumab monotherapy or combination therapy (ranibizumab plus laser photocoagulation) compared with laser monotherapy for the treatment of visual impairment due to diabetic macular edema (DME). Methods A Markov model was developed in which patients moved between health states defined by best-corrected visual acuity (BCVA) intervals and an absorbing 'death' state. The population of interest was patients with DME due to type 1 or type 2 diabetes mellitus. Baseline characteristics were based on those of participants in the RESTORE study. Main outputs were costs (in 2013 CA$) and health outcomes (in quality-adjusted life-years [QALYs]) and the incremental cost-effectiveness ratio (ICER) was calculated. This cost-utility analysis was conducted from healthcare system and societal perspectives in Quebec. Results From a healthcare system perspective, the ICERs for ranibizumab monotherapy and combination therapy vs laser monotherapy were CA$24 494 and CA$36 414 per QALY gained, respectively. The incremental costs per year without legal blindness for ranibizumab monotherapy and combination therapy vs laser monotherapy were CA$15 822 and CA$20 616, respectively. Based on the generally accepted Canadian ICER threshold of CA$50 000 per QALY gained, ranibizumab monotherapy and combination therapy were found to be cost-effective compared with laser monotherapy. From a societal perspective, ranibizumab monotherapy and combination therapy provided greater benefits at lower costs than laser monotherapy (ranibizumab therapy dominated laser therapy). Conclusions Ranibizumab monotherapy and combination therapy resulted in increased quality-adjusted survival and time without legal blindness and lower costs from a societal perspective compared with laser monotherapy.

Pan-retinal photocoagulation and other forms of laser treatment and drug therapies for non-proliferative diabetic retinopathy: systematic review and economic evaluation.

BACKGROUND: Diabetic retinopathy is an important cause of visual loss. Laser photocoagulation preserves vision in diabetic retinopathy but is currently used at the stage of proliferative diabetic retinopathy (PDR). OBJECTIVES: The primary aim was to assess the clinical effectiveness and cost-effectiveness of pan-retinal photocoagulation (PRP) given at the non-proliferative stage of diabetic retinopathy (NPDR) compared with waiting until the high-risk PDR (HR-PDR) stage was reached. There have been recent advances in laser photocoagulation techniques, and in the use of laser treatments combined with anti-vascular endothelial growth factor (VEGF) drugs or injected steroids. Our secondary questions were: (1) If PRP were to be used in NPDR, which form of laser treatment should be used? and (2) Is adjuvant therapy with intravitreal drugs clinically effective and cost-effective in PRP? ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) for efficacy but other designs also used. DATA SOURCES: MEDLINE and EMBASE to February 2014, Web of Science. REVIEW METHODS: Systematic review and economic modelling. RESULTS: The Early Treatment Diabetic Retinopathy Study (ETDRS), published in 1991, was the only trial designed to determine the best time to initiate PRP. It randomised one eye of 3711 patients with mild-to-severe NPDR or early PDR to early photocoagulation, and the other to deferral of PRP until HR-PDR developed. The risk of severe visual loss after 5 years for eyes assigned to PRP for NPDR or early PDR compared with deferral of PRP was reduced by 23% (relative risk 0.77, 99% confidence interval 0.56 to 1.06). However, the ETDRS did not provide results separately for NPDR and early PDR. In economic modelling, the base case found that early PRP could be more effective and less costly than deferred PRP. Sensitivity analyses gave similar results, with early PRP continuing to dominate or having low incremental cost-effectiveness ratio. However, there are substantial uncertainties. For our secondary aims we found 12 trials of lasers in DR, with 982 patients in total, ranging from 40 to 150. Most were in PDR but five included some patients with severe NPDR. Three compared multi-spot pattern lasers against argon laser. RCTs comparing laser applied in a lighter manner (less-intensive burns) with conventional methods (more intense burns) reported little difference in efficacy but fewer adverse effects. One RCT suggested that selective laser treatment targeting only ischaemic areas was effective. Observational studies showed that the most important adverse effect of PRP was macular oedema (MO), which can cause visual impairment, usually temporary. Ten trials of laser and anti-VEGF or steroid drug combinations were consistent in reporting a reduction in risk of PRP-induced MO. LIMITATION: The current evidence is insufficient to recommend PRP for severe NPDR. CONCLUSIONS: There is, as yet, no convincing evidence that modern laser systems are more effective than the argon laser used in ETDRS, but they appear to have fewer adverse effects. We recommend a trial of PRP for severe NPDR and early PDR compared with deferring PRP till the HR-PDR stage. The trial would use modern laser technologies, and investigate the value adjuvant prophylactic anti-VEGF or steroid drugs. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013005408. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

A United Kingdom-based economic evaluation of ranibizumab for patients with retinal vein occlusion (RVO).

OBJECTIVE: This study compares the cost-effectiveness of intravitreal ranibizumab vs observation and/or laser photocoagulation for treatment of macular edema secondary to retinal vein occlusion in a UK-based model. METHODS: A Markov model was constructed using transition probabilities and frequency of adverse events derived using data from the BRAVO, CRUISE, and HORIZON trials. Outcomes associated with treatments and health states were combined to predict overall health costs and outcomes for cohorts treated with each option. RESULTS: In branch retinal vein occlusion, ranibizumab produced a gain of 0.518 quality-adjusted life years at an incremental cost of £8141, compared with laser photocoagulation. The incremental cost-effectiveness ratio was £15,710 per quality-adjusted life year, and the incremental cost per month free from blindness was £658. In central retinal vein occlusion, ranibizumab produced a gain of 0.539 quality-adjusted life years at an incremental cost of £9216, compared with observation only. The incremental cost-effectiveness ratio was £17,103, and the incremental cost per month free from blindness was £423. CONCLUSIONS: These incremental cost-effectiveness ratios are below the £20,000-30,000 range typically accepted as a threshold for cost-effectiveness. This suggests that ranibizumab may be regarded as a cost-effective therapy for patients with macular edema secondary to retinal vein occlusion, relative to grid laser photocoagulation (for BRVO) and observation (for CRVO). Limitations include sparse data for utilities associated with the severity of visual impairment in the WSE in patients with RVO. A lack of direct comparative evidence between ranibizumab and the dexamethasone intravitreal implant for the treatment of BRVO and CRVO and the infeasibility of an indirect comparison due to significant heterogeneity in trial designs prevented the inclusion of this treatment as a comparator in the Markov model.

Projected cost comparison of Trabectome, iStent, and endoscopic cyclophotocoagulation versus glaucoma medication in the Ontario Health Insurance Plan.

PURPOSE: To compare the direct cost of treating glaucoma patients with Trabectome, iStent, and endoscopic cyclophotocoagulation (ECP) versus topical medications in Ontario, Canada. Costs are projected over a 6-year period, and presented on a per-patient level from the perspective of the Ontario Health Insurance Plan (OHIP). METHODS: The per-bottle cost of each medication was obtained from the 2011 Ontario Drug Benefit (ODB) formulary. A wastage adjustment fee was added to the cost, as was a pharmacy markup, and an ODB dispensing fee. Previously published medication prescription rates were used to determine the frequency with which each medication is prescribed. We estimated the overall cost by taking a weighted average of the cost of each class of glaucoma medications.The cost of each glaucoma device was determined by contacting local distributors. We then added the cost of disposables used during surgery (viscoelastic and keratome) to the cost of each procedure. Start-up costs for each device and surgeons' fees were excluded from the overall cost. RESULTS: At 6 years, treatment with the Trabectome offered a cumulative cost savings of $279.23, $1572.55, and $2424.71 per patient versus monodrug, bidrug, and tridrug therapy, respectively. A cumulative cost difference of -$20.77, $1272.55, and $2124.71 per patient were found when comparing iStent versus monodrug, bidrug, and tridrug therapy, respectively. Treatment with ECP yielded a cost savings of $779.23, $2072.55, and $2924.71 per patient versus monodrug, bidrug, and tridrug therapy, respectively. CONCLUSIONS: Over a projected period of 6 years, the Trabectome, iStent, and ECP may all offer a modest cost savings to OHIP versus the cost of glaucoma medication. Further analysis of direct and indirect costs to patients as well as quality of life assessments will help further delineate the role of these treatments in the glaucoma treatment paradigm.

The cost of glaucoma care provided to Medicare beneficiaries from 2002 to 2009.

PURPOSE: To estimate payments for glaucoma care among Medicare beneficiaries from 2002 to 2009. DESIGN: Database study. PARTICIPANTS: Data from a 5% random sample of Medicare billing information from 2002 to 2009. METHODS: Medicare beneficiaries, aged 65 years or older, with both Parts A and B fee-for-service (FFS) enrollment comprised the annual denominator. For each year, we included those with a defined glaucoma diagnostic code linked to a glaucoma visit, diagnostic test, or laser/surgical procedure. Open-angle, angle-closure, and other glaucoma were categorized separately. Claims were classified into glaucoma care, other eye care, and other medical care. MAIN OUTCOME MEASURES: Cost of glaucoma care in the Medicare Fee-for-Service Population. RESULTS: In 2009, total glaucoma payments by Medicare were $37.4 million for this subset, for an overall estimated cost of $748 million, or 0.4% of an estimated cost of $192 billion for all Medicare FFS payments. Office visits comprised approximately one half, diagnostic testing was approximately one-third, and surgical and laser procedures were approximately 10% of glaucoma-related costs. Coded open-angle glaucoma (OAG) and OAG suspects accounted for 87.5% of glaucoma costs, whereas cost per person was highest in "other glaucoma." In 2009, <3% of patients with OAG underwent incisional surgery and approximately 5% had laser trabeculoplasty. Laser iridotomy was the highest cost category among patients with angle-closure glaucoma, whereas office visits was the highest cost category among the "other glaucoma" group. The total cost of nonglaucoma eye care for patients with glaucoma was 67% higher than their glaucoma care costs; these were chiefly costs for cataract surgery and treatment of retinal diseases. From 2002 to 2009, FFS glaucoma care costs calculated in 2009 dollars were stable and cost per person per year in 2009 dollars decreased from $242 to $228 (P = 0.01 by test for linear trend). CONCLUSIONS: Annual glaucoma care costs per person decreased in constant dollars from 2002 to 2009. Cataract and retinal eye care for patients with glaucoma substantially exceeded the cost of their glaucoma care each year. Visit payments represented the largest category of costs.

Cost-effectiveness of various interventions for newly diagnosed diabetic macular edema.

OBJECTIVE: Anti-vascular endothelial growth factor therapies have revolutionized the treatment of clinically significant diabetic macular edema (CSDME); yet these agents are expensive, and whether they are cost-effective is unclear. The purpose of this study is to determine the most cost-effective treatment option for patients with newly diagnosed CSDME: focal laser photocoagulation alone (L), focal laser plus intravitreal ranibizumab (L+R), focal laser plus intravitreal bevacizumab (L+B), or focal laser plus intravitreal triamcinolone (L+T) injections. DESIGN: Cost-effectiveness analysis. PARTICIPANTS: Hypothetical cohort of 57-year-old patients with newly diagnosed CSDME. METHODS: By using a Markov model with a 25-year time horizon, we compared the incremental cost-effectiveness of treating patients with newly diagnosed CSDME using L, L+R, L+B, or L+T. Data came from the DRCRnet randomized controlled trial, the Medicare fee schedule, and the medical literature. MAIN OUTCOME MEASURES: Costs, quality-adjusted life years (QALYs), and incremental costs per QALY gained. RESULTS: Compared with L, the incremental cost-effectiveness of L+R and L+B was $89903/QALY and $11138/QALY, respectively. L+T was dominated by L. A probabilistic sensitivity analysis demonstrated that, at a willingness to pay (WTP) of $50000/QALY, L was approximately 70% likely to be the preferred therapy over L+R and L+T. However, at a WTP of $100000/QALY, more than 90% of the time, L+R therapy was the preferred therapy compared with L and L+T. In the probabilistic sensitivity analysis, L+B was found to be the preferred therapy over L and L+T for any WTP value >$10000/QALY. Sensitivity analyses revealed that the annual risk of cerebrovascular accident would have to be at least 1.5% higher with L+B than with L+R for L+R to be the preferred treatment. In another sensitivity analysis, if patients require <8 injections per year over the remainder of the 25-year time horizon, L+B would cost <$100000/QALY, whereas L+R would be cost-effective at a WTP of $100000/QALY if patients require fewer than 0.45 injections per year after year 2. CONCLUSIONS: With bevacizumab and ranibizumab assumed to have equivalent effectiveness and similar safety profiles when used in the management of CSDME, bevacizumab therapy confers the greatest value among the different treatment options for CSDME. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

The cost-utility of telemedicine to screen for diabetic retinopathy in India.

PURPOSE: To assess the cost-effectiveness of a telemedicine diabetic retinopathy (DR) screening program in rural Southern India that conducts 1-off screening camps (i.e., screening offered once) in villages and to assess the incremental cost-effectiveness ratios of different screening intervals. DESIGN: A cost-utility analysis using a Markov model. PARTICIPANTS: A hypothetical cohort of 1000 rural diabetic patients aged 40 years who had not been previously screened for DR and who were followed over a 25-year period in Chennai, India. METHODS: We interviewed 249 people with diabetes using the time trade-off method to estimate utility values associated with DR. Patient and provider costs of telemedicine screening and hospital-based DR treatment were estimated through interviews with 100 diabetic patients, sampled when attending screening in rural camps (n = 50) or treatment at the base hospital in Chennai (n = 50), and with program and hospital managers. The sensitivity and specificity of the DR screening test were assessed in comparison with diagnosis using a gold standard method for 346 diabetic patients. Other model parameters were derived from the literature. A Markov model was developed in TreeAge Pro 2009 (TreeAge Software Inc, Williamstown, MA) using these data. MAIN OUTCOME MEASURES: Cost per quality-adjusted life-year (QALY) gained from the current teleophthalmology program of 1-off screening in comparison with no screening program and the cost-utility of this program at different screening intervals. RESULTS: By using the World Health Organization threshold of cost-effectiveness, the current rural teleophthalmology program was cost-effective ($1320 per QALY) compared with no screening from a health provider perspective. Screening intervals of up to a frequency of screening every 2 years also were cost-effective, but annual screening was not (>$3183 per QALY). From a societal perspective, telescreening up to a frequency of once every 5 years was cost-effective, but not more frequently. CONCLUSIONS: From a health provider perspective, a 1-off DR telescreening program is cost-effective compared with no screening in this rural Indian setting. Increasing the frequency of screening up to 2 years also is cost-effective. The results are dependent on the administrative costs of establishing and maintaining screening at regular intervals and on achieving sufficient coverage.

Clinical applications of cost analysis of diabetic macular edema treatments.

OBJECTIVE: To apply cost-benefit analyses in specific circumstances in which the results of multiple modalities of treating diabetic macular edema (DME) are similar, as a basis for considering economic ramifications in clinically relevant applications. DESIGN: A model of resource use, outcomes, and cost-effectiveness and utility. PARTICIPANTS: There were no participants. METHODS: Results from published clinical trials (index studies) of laser, intravitreal corticosteroids, intravitreal anti-vascular endothelial growth factor (VEGF) agents, and vitrectomy trials were used to ascertain visual benefit and clinical protocols of patients with DME. Calculations followed from the costs of 1 year of treatment for each modality and the visual benefits as ascertained. MAIN OUTCOME MEASURES: Visual acuity (VA) saved, cost of therapy, cost per line saved, cost per line-year saved, and costs per quality-adjusted life years (QALYs) saved. RESULTS: Four specific situations were observed or analyzed: (1) Treatment results for DME causing VA loss <20/200 show at least as much visual benefit for intravitreal triamcinolone (IVTA) versus laser; (2) a subgroup analysis of pseudophakic DME eyes shows equivalent visual results with anti-VEGF treatment versus laser combined with IVTA; (3) eyes with VA of ≥ 20/32 have been studied only by laser; and (4) less frequent use of aflibercept yields equivalent visual results as more frequent treatment. When the results are equivalent, opting for the less-expensive treatment option could yield cost savings of 40% to 88%. CONCLUSIONS: Cost-effectiveness analyses can be clinically relevant and may be considered when formulating and applying treatment strategies for some subsets of patients with DME. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.