Assessment of Prevalence and Risk Factors for Diabetic Retinopathy in Patients with Type 1 and Type 2 Diabetes Examined at a Tertiary Care.

Introduction: Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus and the leading cause of visual impairment and blindness. The aim of the study was to estimate and compare the prevalence of DR and to determine an association between DR and systemic risk factors in hospitalized type 1 (DMT1) and type 2 (DMT2) diabetic patients. Material and methods: We analyzed 260 patients with diabetes, 43 with DMT1 and 217 with DMT2. The following data were collected: age, gender, type and duration of diabetes, glycemic control, blood pressure, estimated glomerular filtration rate, ophthalmologic examinations and routine biochemical parameters. Results: Out of the total number of 260 patients, 77 (29.6%) had non-proliferative DR (NPDR), 21 (8.1%) had proliferative DR (PDR), 29 (11.1%) had diabetic macular edema (DME), and 69 (23.5%) had diabetic cataracts. Forty-three (16.5%) patients were previously diagnosed with DMT1 and 217 (83.5%) with DMT2. The duration of diabetes was not significantly longer in DMT1 (12.8±11.2 years) in comparison to DMT2 (11.07±8.1 years). The prevalence of NPDR and PDR did not differ statistically in either groups. DME was more prevalent in DMT2 than in DMT1 (P<0.05). Diabetic cataract was found in 26.7% vs. 6.7% of patients with DMT2 and DMT1, respectively (p<0.01). The duration of diabetes significantly correlated with NPDR and PDR in DMT1 (r=o.31, p<0.05; r=0.55, p<0.001, respectively). In DMT2, significant correlations were found between the duration of diabetes and cataract, NPDR, PDR and DME (r=0.31, p<0.001; r=0.43 p<0.01, r=0.16 p<0.05 and r=0.20 p<0.01, respectively). Fasting plasma glucose (FPG) significantly correlated with PDR (r=0.258, p<0.05), while HbA1c with DME (r= 0.15 p<0.05). Conclusion: The duration of diabetes and hyperglycemia were associated with DR in both types of diabetes.

Cost-Utility Comparison of Bevacizumab and Aflibercept in the Treatment of Central or Hemiretinal Vein Occlusion in the SCORE2 Trial.

Importance: Retinal vein occlusion is the second most common retinal vascular disease. Bevacizumab was demonstrated in the Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2) to be noninferior to aflibercept with respect to visual acuity in study participants with macular edema due to central retinal vein occlusion (CRVO) or hemiretinal vein occlusion (HRVO) following 6 months of therapy. In this study, the cost-utility of bevacizumab vs aflibercept for treatment of CRVO is evaluated. Objective: To investigate the relative cost-effectiveness of bevacizumab vs aflibercept for treatment of macular edema associated with CRVO or HRVO. Design, Setting, and Participants: This economic evaluation study used a microsimulation cohort of patients with clinical and demographic characteristics similar to those of SCORE2 participants and a Markov process. Parameters were estimated and validated using a split-sample approach of the SCORE2 population. The simulated cohort included 5000 patients who were evaluated 100 times, each with a different set of characteristics randomly selected based on the SCORE2 trial. SCORE2 data were collected from September 2014 October 2019, and data were analyzed from October 2019 to July 2021. Interventions: Bevacizumab (followed by aflibercept among patients with a protocol-defined poor or marginal response to bevacizumab at month 6) vs aflibercept (followed by a dexamethasone implant among patients with a protocol-defined poor or marginal response to aflibercept at month 6). Main Outcomes and Measures: Incremental cost-utility ratio. Results: The simulation demonstrated that patients treated with aflibercept will have an expected cost $18 127 greater than those treated with bevacizumab in the year following initiation. When coupled with the lack of clinical superiority over bevacizumab (ie, patients treated with bevacizumab had a gain over aflibercept in visual acuity letter score of 4 in the treated eye and 2 in the fellow eye), these results demonstrate that first-line treatment with bevacizumab dominated aflibercept in the simulated cohort of SCORE2 participants. At current price levels, aflibercept would be considered the preferred cost-effective option only if treatment restored the patient to nearly perfect health. Conclusions and Relevance: While there will be some patients with CRVO-associated or HRVO-associated macular edema who will benefit from first-line treatment with aflibercept rather than bevacizumab, given the minimal differences in visual acuity outcomes and large cost differences for bevacizumab vs aflibercept, first-line treatment with bevacizumab is cost-effective for this condition.

Cost-Effectiveness of Dexamethasone Intravitreal Implant in Naïve and Previously Treated Patients with Diabetic Macular Edema.

PURPOSE: To compare the direct costs associated with the dexamethasone intravitreal implant (DEX-i) in treatment-naïve and previously treated eyes with diabetic macular edema (DME) in a real clinical setting. METHODS: Retrospective and single-center study conducted in a real clinical scenario. Consecutive DME patients, either naïve or previously treated with vascular endothelial growth factor inhibitors (anti-VEGF), who received treatment with one or more DEX-i between May 2015 and December 2020, and who were followed-up for a minimum of 12 months, were included in the study. The cost analysis was performed from the perspective of the Andalusian Regional Healthcare Service. The primary effectiveness endpoint was the probability of achieving an improvement in best-corrected visual acuity (BCVA) ≥ 15 ETDRS letters after 1 year of treatment. The incremental cost-effectiveness ratio (ICER) of different improvements in BCVA was calculated. RESULTS: Forty-nine eyes, twenty-eight (57.1%) eyes from the treatment-naïve group and twenty-one (42.9%) from the previously treated group, were included in the analysis. The total cost of one year of treatment was significantly lower in the treatment-naïve eyes than in the previously treated eyes [Hodges-Lehmann median difference: EUR 819.1; 95% confidence interval (CI): EUR 786.9 to EUR 1572.8; p < 0.0001]. The probability of achieving a BCVA improvement of ≥15 letters at month 12 was significantly greater in the treatment-naïve group than in the previously treated group (rate difference: 0.321; 95% CI: 0.066 to 0.709; p = 0.0272). The Cochran-Mantel-Haenszel Odds Ratio of achieving a BCVA improvement of ≥15 letters at month 12 was 3.55 (95% CI: 1.09 to 11.58; p = 0.0309). In terms of ICER, the treatment-naïve group showed cost savings of EUR 7704.2 and EUR 5994.2 for achieving an improvement in BCVA ≥ 15 letters at month 12 and at any of the measured time points, respectively. CONCLUSIONS: DEX-i was found to be more cost-effective in treatment-naïve eyes than in those previously treated with anti-VEGF. Further studies are needed to determine the most cost-effective treatment based on patient profile.

Novel optical coherence tomography angiography biomarkers in the diagnosis and assessment of diabetic macular edema and diabetic macular ischemia in patients with non-proliferative diabetic retinopathy.

Purpose: The present study aims to determine the macular and choroidal optical coherence tomography angiography (OCTA) biomarkers in the assessment and monitoring of diabetic macular edema (DME) and diabetic macular ischemia (DMI) in patients with non-proliferative diabetic retinopathy (NPDR). Methods: In this cohort study, a total of 176 eyes of 110 patients with NPDR were investigated at our institute over a period of 10 months. Eyes were divided into four groups based on the severity of NPDR. Each eye was subjected to OCTA (Topcon 3D OCT-1 Maestro2) macula 6 × 6 mm2 en face. It features IMAGEnet 6 software for dynamic viewing of OCTA and imaging data. Four OCTA biomarkers for the macula were identified: foveal avascular zone area (FAZ area), foveal avascular zone contour irregularity (FAZ-CI), capillary dropout areas (CDA), and perifoveal intercapillary areas (PICA). The choroidal OCTA biomarker was the number of choroidal circulation flow voids (CCFV). For all analyses, P < 0.05 was considered statistically significant. Results: Increase in FAZ area and number of CDA were statistically significant (p < 0.0001) with an increase in central foveal thickness, suggesting a correlation of ischemic changes with an increase in DME. FAZ-CI, enlarged PICA, and CCFV were significantly associated with more severe NPDR patients. Conclusion: A correlation between DME and DMI in a patient of NPDR and its progression can be evaluated in a single visit. A unique feature of our study is it revealed novel diagnostic biomarkers of OCTA for DMI and DME.

Quantitative assessment of OCT and OCTA parameters in diabetic retinopathy with and without macular edema: single-center cross-sectional analysis.

Aim: The retinal and choroidal parameters were analyzed to understand the impairment of microcirculation of both retina and choroid in patients with diabetic retinopathy (DR). Methods: Fifty-five treatment-naive non-proliferative diabetic retinopathy (NPDR) patients (75 eyes) with type 2 diabetes mellitus (T2DM), including 28 patients (36 eyes) with diabetic macular edema (DME) and 27 patients (39 eyes) without DME, and 25 healthy subjects (47 eyes) were enrolled in this study. The following parameters of DR patients with and without DME were evaluated: the foveal avascular zone area (FAZ-a), FAZ perimeter (FAZ-p), FAZ circularity index (FAZ-CI), total subfoveal choroidal area (TCA), luminal area (LA), stromal area (SA), choroidal vascularity index (CVI), choriocapillaris flow area percentage, superficial capillary plexus (SCP), and deep capillary plexus (DCP). Results: SCP, DCP, and the percentage of choriocapillaris flow area were significantly different between DR patients with and without DME. The DR patients presented lower LA, CVI, and FAZ-CI compared to those of healthy controls (all p < 0.05). The percentage of choriocapillaris flow area in DR patients with and without DME was significantly lower than that in healthy controls (p < 0.05). SCP and DCP were significantly correlated with FAZ-a and FAZ-p but presented insignificant associations with FAZ-CI. Conclusions: Optical coherence tomography (OCT) and OCT angiography (OCTA) parameters, such as LA, CVI, FAZ-CI, and the percentage of choriocapillaris flow area, were reduced compared to those in controls, indicating that the microcirculations of the retina and choroid in the macular area were impaired in DR patients with DME and without DME.

Eficacia y seguridad del implante intravítreo de dexametasona de liberación prolongada sostenida para el tratamiento de pacientes adultos con edema macular secundario a oclusión venosa retiniana con disminución de la agudeza visual y/o incremento o mantenimiento del grosor macular a pesar del uso de tres inyecciones de bevacizumab / Efficacy and safety of intravitreal sustained-release dexamethasone implant for the treatment of adult patients with macular edema secondary to retinal vein occlusion with decreased visual acuity and/or increased or maintained macular thickness despite the use of three injections of bevacizumab

ANTECEDENTES: En el marco de la metodología ad hoc para evaluar solicitudes de tecnologías sanitarias, aprobada mediante Resolución de Instituto de Evaluación de Tecnologías en Salud e Investigación N' 111-IETSI-ESSALUD-2021 se ha elaborado el presente dictamen. el cual expone la evaluación de la eficacia y seguridad del implante intravítreo de dexametasona de liberación prolongada sostenida para el tratamiento de pacientes adultos con edema macular secundario a oclusión venosa retiniana con disminución de la agudeza visual y/o incremento o mantenimiento del grosor macular a pesar del uso de tres inyecciones de bevacizumab. Así. la médica Fiorella Norabuena Mautino. especialista en oftalmología del Servicio de Retina, a través del Comité Farmacoterapéutico del Hospital Nacional Edgardo Rebagliati Martins y siguiendo la Directiva N' 003-IETSI-ESSALUD-2016, envía al Instituto de Evaluación de Tecnologías en Salud e Investigación - IETSI la solicitud de autorización de uso del producto farmacéutico dexametasona (implante intravítreo) no incluido en el Petitorio Farmacológico de EsSalud. ASPECTOS GENERALES: La oclusión venosa retiniana (OVR), una obstrucción parcial o completa del sistema venoso retinal, es considerada la segunda causa más común de trastorno vascular de la retina (Cugati et al., 2006; PAAO, 2019), y es una causa importante de pérdida de la visión en adultos a nivel mundial (Rogers et al., 2010: Song et al., 2019). En el 2015, se estimó que la prevalencia global de la OVR en personas de entre 30 y 89 años fue de 0.77 % (Song et al., 2019). Los dos tipos más comunes de OVR, son la oclusión de la rama venosa de la retina (ORVR), que ocurre en la vena retinal distal y ocasiona hemorragia en un vaso pequeño de la retina; y la oclusión de la vena central de la retina (OVCR), que ocurre en la vena retinal proximal y ocasiona hemorragia en toda la retina (Han & Ahmad, 2021). En un estudio realizado con datos de Europa, Asia, Australia y Estados Unidos se reporta que la prevalencia ajustada por edad y sexo de la ORVR es de 3.77 por 1000 personas, y de la OVCR es de 0.65 por 1000 personas. METODOLOGÍA: Se realizó una búsqueda bibliográfica exhaustiva con el objetivo de identificar la mejor evidencia sobre la eficacia y seguridad del uso de IIDLPS en el tratamiento de pacientes adultos con EM secundario a ORVR u OVCR con disminución de la AV y/o incremento o mantenimiento del grosor macular a pesar del uso de tres inyecciones de bevacizumab. La búsqueda bibliográfica se realizó en las bases de datos PubMed, The Cochrane Library, LILACS y The Web of Science. Adicionalmente, se amplió la búsqueda revisando la evidencia generada por grupos internacionales que realizan revisiones sistemáticas. evaluaciones de tecnologías sanitarias y guías de práctica clínica. tales como The National Institute for Health and Care Excellence (NICE). RESULTADOS: De la búsqueda bibliográfica, se incluyó una GPC elaborada por The Royal College of Ophthalmologists (RCO) (The Royal College of Ophthalmologists. 2022). y tres estudios retrospectivos que evaluaron el cambio de bevacizumab a IIDLPS (Chiquet et al.. 2016: Lee et al.. 2017: Sharareh et al., 2013). Además se incluyeron dos GPC que fueron sugeridas por los especialistas de EsSalud, elaboradas por The European Society of Retina Specialists (EURETINA) (Schmidt-Erfurth et al., 2019) y la Sociedad Española de Retina y Vítreo (SERV) (SERV, 2015). No se identificaron RS con MA ni ETS que respondan a la pregunta PICO del presente dictamen. CONCLUSIÓN: Por lo expuesto, el Instituto de Evaluación de Tecnologías en Salud e Investigación aprueba el uso de implante intravitreo de dexametasona de liberación prolongada sostenida (IIDLPS) para el tratamiento de pacientes adultos con edema macular (EM) secundario a oclusión de la vena central de la retina (OVCR) u oclusión de la rama venosa de la retina (ORVR) con disminución de la AV y/o incremento o mantenimiento del grosor macular a pesar del uso de tres inyecciones de bevacizumab. como producto farmacéutico no incluido en el Petitorio Farmacológico de EsSalud. según lo establecido en el Anexo N° 1. La vigencia del presente dictamen preliminar es de 1 año a partir de la fecha de publicación. La continuación de dicha aprobación está sujeta a la evaluación de los resultados obtenidos y de nueva evidencia que pueda surgir en el tiempo.

Choroidal Assessment in Patients with Type 2 Diabetes Mellitus and Non-Proliferative Diabetic Retinopathy by Swept-Source Ocular Coherence Tomography and Image Binarization.

Background and Objectives: The aim of this study was to evaluate choroidal structure and vascularity indices in patients with non-proliferative diabetic retinopathy (NPDR). Materials and Methods: Sixty-three eyes from sixty-three patients were evaluated: 21 from healthy subjects, 20 with diabetes mellitus (DM) and no diabetic retinopathy (DR), and 22 with DM and non-proliferative diabetic retinopathy without diabetic macular edema (DME). Each patient underwent ocular examination, macular swept-source ocular coherence tomography (SS-OCT) imaging, glycemic control, and systemic high blood pressure (HBP) evaluation. Subfoveal choroidal thickness (SF-CT) was manually assessed on a line scan. Line scan OCT images were exported to ImageJ program. The areas under a 1.5, 3 and 6 mm horizontal line centered on the fovea were assessed by converting the OCT images to binary images, and total choroidal area (TCA), luminal area (LA), stromal area (SA), LA:SA ratio, and choroidal vascularity index (CVI) were evaluated. SF-CT and choroidal parameters were compared between groups, and correlations with ocular and systemic factors were analyzed. Results: SF-CT, TCA, LA, and SA were similar between groups. CVIs were significantly different between groups for all three studied areas (CVI-1.5: 66.21% vs. 66.06% vs. 63.74%, p = 0.003; CVI-3: 65.88% vs. 66.46% vs. 63.79%, p = 0.008; CVI-6: 64.79% vs. 65.40% vs. 63.61%, p = 0.032). NPDR patients had significantly lower CVIs compared to DM patients (p < 0.05). No association of choroidal parameters with glycemic control, DM duration and HBP was found significant (p < 0.05). Conclusions: Choroidal assessment by SS-OCT and image binarization in healthy subjects, subjects with DM without DR, and subjects with DM and NPDR indicated that CVI changes were identifiable and significant in early DR. The lack of association with ocular and systemic factors suggest that CVIs are reliable assessment parameters of choroidal vascular structure.

Assessment of Diabetic Choroidopathy Using Ultra-Widefield Optical Coherence Tomography.

Purpose: The purpose of this study was to investigate a confocal scanning laser ophthalmoscopy (cSLO) ultra-widefield (UWF) swept-source optical coherence tomography (S-SOCT) in assessment of diabetic choroidopathy and to evaluate the agreement of measurements with a spectral-domain OCT (SD-OCT) instrument. Methods: We conducted a cross-sectional study of patients with diabetes evaluating the choroidal vascularity index (CVI) in the nasal, temporal, and central macula segments of a UWF SS-OCT scan centered to the fovea. UWF pseudocolored fundus images were used for diabetic retinopathy (DR) severity staging. The CVI values were compared between different degrees of severity of DR and different posterior-pole sectors with linear mixed models. Central macula CVI measurements were repeated on SD-OCT scans; the interobserver intraclass coefficient (ICC) was calculated between SS-OCT and SD-OCT. Results: A total of 151 eyes of 85 patients were included. The CVI values decreased from nonproliferative DR to proliferative DR, with high-risk proliferative DR having significantly lower CVI values than moderate to severe nonproliferative DR (P = 0.03). The central macula region was the most evidently affected; the nasal sector was the least affected. The agreement between SS-OCT and SD-OCT was moderate (ICC = 0.50). Conclusions: Diabetic choroidopathy progresses with worsening of DR toward proliferative disease; choroidal depletion is more prominent in the macula. Caution is recommended in comparing CVI values between different devices. Translational Relevance: Choroidal vascularity informs about the severity of DR and its complications, such as macular edema. The agreement between readers and between instruments may be suboptimal in certain cases.

Cost-effectiveness analysis of intravitreal aflibercept in the treatment of diabetic macular edema in China.

Aim: To evaluate the cost-effectiveness of intravitreal aflibercept compared with macular laser photocoagulation and ranibizumab for diabetic macular edema (DME) in China. Methods: A Markov model was developed to reflect the vision changes in DME patients. Parameters were estimated from VIVID-EAST trial data, published literature and physician surveys. Results: In a 20-year horizon, intravitreal aflibercept was associated with 7.825 quality-adjusted life years (QALYs) and 217,841 Chinese Yuan Renminbi (CNY), laser photocoagulation was associated with 7.189 QALYs and 135,489 CNY, and ranibizumab was associated with 7.462 QALYs and 222,477 CNY. The incremental cost-effectiveness ratios were 129,397 CNY/QALY and -12,774 CNY/QALY for intravitreal aflibercept versus laser photocoagulation and ranibizumab, respectively. Conclusion: Intravitreal aflibercept was considered as a cost-effective strategy for DME when compared with laser photocoagulation; it was considered as a dominant strategy when compared with ranibizumab.

Healthcare resource use and costs of diabetic macular oedema for patients with antivascular endothelial growth factor versus a dexamethasone intravitreal implant in Korea: a population-based study.

OBJECTIVES: To estimate the costs and healthcare resources of patients with diabetic macular oedema (DME) who received intravitreal antivascular endothelial growth factor (anti-VEGF) agents or a dexamethasone intravitreal implant (DEX-implant) in Korea. DESIGN: Retrospective cohort study. SETTING: The Korean National Health Insurance claim data from 1 January 2015 to 30 June 2017 were retrieved from the Health Insurance Review and Assessment Service. PARTICIPANTS: Adult patients with DME who were diagnosed with diabetic retinopathy or DME and received ranibizumab, aflibercept or a DEX-implant in conjunction with intravitreal injection were included. Patients whose primary diagnoses were age-related macular degeneration or retinal vein occlusion were excluded. MAIN OUTCOME MEASURES: Healthcare resource utilisation and costs related to DME in the 12-month postindex period. RESULTS: During the study period, 182 patients and 414 patients were identified in the anti-VEGF and DEX-implant groups, respectively, and there was no significant difference in the demographic characteristics between the two groups. The outpatient eye care-related medical costs were US$3002.33 for the anti-VEGF group vs US$2250.35 for the DEX-implant group (p<0.0001). After adjusting the relevant covariates based on the generalised linear model, the estimated outpatient eye care-related medical costs were 33% higher in the anti-VEGF group than in the DEX-implant group (p<0.0001, 95% CI 22% to 45%). The utilisation pattern of the two groups showed no significant difference except for the number of intravitreal injections, which was higher in the anti-VEGF group (2.69±2.29) than in the DEX-implant group (2.09±1.37, p<0.001). CONCLUSION: The average annual eye-related medical cost of the DEX-implant group was significantly lower than that of the anti-VEGF group during the study period, which was mainly due to decreased utilisation of eye care-related injections. Further long-term studies are needed.

Short-Term Assessment of Intravitreal Dexamethasone Implant Using Enhanced-Depth Image Optical Coherence Tomography and Optical Coherence Tomography Angiography in Patients with Retinal Vascular Diseases.

INTRODUCTION: To evaluate the short-term efficacy and safety of intravitreal dexamethasone implant (IDI) in patients with macular oedema associated with diabetic retinopathy (DR) and retinal vein occlusion (RVO) using enhanced-depth image optical coherence tomography (EDI-OCT) and to estimate the effect of dexamethasone on the choroid and the retinal vascular network using OCT angiography (OCTA). METHODS: Fifteen eyes in 15 patients with macular oedema secondary to diabetes (DR, n = 8) or retinal vein occlusion (RVO, n = 7) were treated with intravitreal injection of sustained-release IDI. Primary efficacy end points were changes in best corrected visual acuity and central macular thickness (CMT). Secondary end points were changes in choroidal thickness and choroidal and retinal vascular networks as determined by OCTA. RESULTS: CMT was significantly reduced from baseline by 3 h after injection (p < 0.01) and improved further during the 3-month follow-up. Visual acuity improvement was consistent with CMT reduction. No alterations in IOP or systemic side effects were observed. OCTA showed improvement from baseline in terms of decreased number and size of cysts and restoration of the retinal vascular network; flow choroidal thickness did not change significantly. CMT and visual acuity variations were similar in the two groups. CONCLUSIONS: CMT reduced as early as 3 h after the injection of IDI, with further reduction during follow-up. Choroidal thickness was unchanged, whereas the vascular retinal network improved from baseline to the end of study. Both EDI-OCT and OCTA were useful in demonstrating the early beneficial effects of IDI on the macula and the perifoveal vascular network. FUNDING: The article processing charges, the open access fee and the medical writing and editorial assistance was funded by Allergan.

The impact of anti-vascular endothelial growth factor agents on visual impairment/blindness prevention in patients with diabetic macular edema and on associated patient and caregiver burden in Japan.

AIMS: To estimate the impact of anti-vascular endothelial growth factor (VEGF) agents on visual impairment and blindness avoided in patients with diabetic macular edema (DME) and on associated patient and caregiver productivity loss in Japan. METHODS: This study compared the impact of current care (estimated at 53.8% utilization of anti-VEGF agents using current data) with that of hypothetical care (characterized by a higher utilization of anti-VEGF agents [80.0%], as estimated by an expert panel) of DME patients. A population-based Markov model (two-eye approach) simulated visual acuity (Early Treatment Diabetic Retinopathy Study [ETDRS] letters) transitions over 5 years with DME treatments (intravitreal aflibercept, ranibizumab, and triamcinolone acetonide, and grid/focal laser) in patients with DME. Patient and caregiver productivity loss was determined using the human capital method. RESULTS: In total, 570,000 DME patients were included in the model over 5 years. Increased utilization of anti-VEGF agents resulted in 6,659 fewer cases of severe visual impairment (SVI; 26-35 ETDRS letters) or blindness (0-25 ETDRS letters) compared with the current care approach (26,023 vs 32,682 cases; 20.38% reduction) over this period. Increased utilization of anti-VEGF agents also contributed to productivity loss savings of ¥12.58 billion (US $115.64 million) (i.e., 17.01%) at the end of year 5. The total overall saving over 5 years was ¥45.83 billion (US $421.27 million) (13.45%). LIMITATIONS: Few Japanese data were available, and assumptions were made for some inputs. Vision changes dependent on the function of both eyes were not studied. Only intravitreal (not sub-Tenon's) injections of triamcinolone were considered in this model. Direct costs were not considered. CONCLUSIONS: Increased utilization of anti-VEGF agents can reduce SVI and legal blindness in patients with DME in Japan. This would also be associated with substantial savings in patient and caregiver productivity loss.

Análisis de impacto presupuestal de ranibizumab comparado con aflibercept, triamcinolona y bevacizumab para tratamiento de pacientes con edema macular secundario a oclusión de la vena central de retina en Colombia / Ranibizumab budget impact analysis compared to aflibercept, triamcinolone and bevacizumab for treatment of patients with macular edema secondary to central retinal vein occlusion in Colombia

Tecnologías evaluadas: Intervención: Ranibizumab; Comparadores: Aflibercept, triamcinolona y bevacizumab. Población: Pacientes con edema macular secundario a oclusión de la vena central de la retina en Colombia. \r\nPerspectiva: Tercer pagado - Sistema General de Seguridad Social en Salud (SGSSS). Horizonte temporal: \r\nEl horizonte temporal de este AIP en el caso base corresponde a un año. Adicionalmente, se reportan las\r\nestimaciones del impacto presupuestal para los años 2 y 3, bajo el supuesto de la inclusión en el POS en el año 1. Costos incluidos: Costo de medicamentos; Costos de procedimientos e insumos. Fuente de costos: SISMED; Manual tarifario ISS 2001. Escenarios: Escenario 1: El costo de los medicamentos permanece igual al actual. El uso de bevacizumab sería de 85%, aflibercept sería del 10%, triamcinolona podría ocupar el 15 % restante Escenario 2: tanto el costo de ranibizumab como el de aflibercept se ajustan al valor de bevacizumab. Ante esta situación, la utilización de aflibercept sería del 50%, ranibizumab y bevacizumab tomarían un 22.5% de participación cada uno y triamcinolona el restante 5%. Resultados: El impacto presupuestal total e incremental al que el sistema de salud colombiano estaría incurriendo al incluir los\r\nmedicamentos ranibizumab, aflibercept, bevacizumab y triamcinolona dentro del plan de beneficios para el tratamiento de edema macular secundario a OVCR bajo las condiciones de caso base este valor sería de 25.716 millones de pesos para el primer año de adopción. Para el segundo y tercer año el impacto incremental sería superior a los 6 y 8 mil millones de pesos respectivamente. (AU)

Efficacy of anti-VEGF and laser photocoagulation in the treatment of visual impairment due to diabetic macular edema: a systematic review and network meta-analysis.

OBJECTIVE: Compare the efficacy of ranibizumab, aflibercept, laser, and sham in the first-line treatment of diabetic macular edema (DME) to inform technology assessments such as those conducted by the UK National Institute for Health and Care Excellence (NICE). DATA SOURCES: MEDLINE, Embase, Cochrane Library, congress abstracts, ClinicalTrials.gov registry and Novartis data on file. INCLUSION CRITERIA: Studies reporting 6- or 12-month results of randomized controlled trials (RCTs) evaluating at least two of ranibizumab 0.5 mg pro re nata, aflibercept 2.0 mg bi-monthly, laser photocoagulation or sham. Study quality was assessed based on likelihood of bias in selection, attrition, detection and performance. OUTCOME MEASURE: Improvement in best-corrected visual acuity (BCVA) measured as the proportion of patients gaining ≥10 letters on the Early Treatment Diabetic Retinopathy Study scale. The outcome was chosen following acceptance by NICE of a Markov model with 10-letter health states in the assessment of ranibizumab for DME. META-ANALYSIS: Bayesian network meta-analyses with fixed and random effects adjusted for differences in baseline BCVA or central retinal thickness. RESULTS: The analysis included 1,978 patients from eight RCTs. The random effects model adjusting for baseline BCVA was the best model based on total residual. The efficacy of ranibizumab was numerically, but not statistically, superior to aflibercept (odds ratio [OR] 1.59; 95% credible interval [CrI], 0.61-5.37). Ranibizumab and aflibercept were statistically superior to laser monotherapy with ORs of 5.50 (2.73-13.16) and 3.45 (1.62-6.84) respectively. The probability that ranibizumab is the most efficacious treatment was 73% compared with 14% for aflibercept, 12% for ranibizumab plus laser, and 0% for laser. LIMITATIONS: Three of the eight RCTs included are not yet published. The models did not adjust for all potential effect modifiers. CONCLUSION: Ranibizumab was non-significantly superior to aflibercept and both anti-VEGF therapies had statistically superior efficacy to laser.

Cost-effectiveness of treatment of diabetic macular edema.

BACKGROUND: Macular edema is the most common cause of vision loss among patients with diabetes. OBJECTIVE: To determine the cost-effectiveness of different treatments of diabetic macular edema (DME). DESIGN: Markov model. DATA SOURCES: Published literature and expert opinion. TARGET POPULATION: Patients with clinically significant DME. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: Laser treatment, intraocular injections of triamcinolone or a vascular endothelial growth factor (VEGF) inhibitor, or a combination of both. OUTCOME MEASURES: Discounted costs, gains in quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS OF BASE-CASE ANALYSIS: All treatments except laser monotherapy substantially reduced costs, and all treatments except triamcinolone monotherapy increased QALYs. Laser treatment plus a VEGF inhibitor achieved the greatest benefit, gaining 0.56 QALYs at a cost of $6975 for an ICER of $12 410 per QALY compared with laser treatment plus triamcinolone. Monotherapy with a VEGF inhibitor achieved similar outcomes to combination therapy with laser treatment plus a VEGF inhibitor. Laser monotherapy and triamcinolone monotherapy were less effective and more costly than combination therapy. RESULTS OF SENSITIVITY ANALYSIS: VEGF inhibitor monotherapy was sometimes preferred over laser treatment plus a VEGF inhibitor, depending on the reduction in quality of life with loss of visual acuity. When the VEGF inhibitor bevacizumab was as effective as ranibizumab, it was preferable because of its lower cost. LIMITATION: Long-term outcome data for treated and untreated diseases are limited. CONCLUSION: The most effective treatment of DME is VEGF inhibitor injections with or without laser treatment. This therapy compares favorably with cost-effective interventions for other conditions. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Hospitalized cardiovascular events in patients with diabetic macular edema.

BACKGROUND: Microvascular and macrovascular complications in diabetes stem from chronic hyperglycemia and are thought to have overlapping pathophysiology. The aim of this study was to investigate the incidence rate of hospitalized myocardial infarctions (MI) and cerebrovascular accidents (CVA) in patients with diabetic macular edema (DME) compared with diabetic patients without retinal diseases. METHODS: This was a retrospective cohort study of a commercially insured population in an administrative claims database. DME subjects (n = 3519) and diabetes controls without retinal disease (n = 10557) were matched by age and gender. Healthcare claims were analyzed for the study period from 1 January 2002 to 31 December 2005. Incidence and adjusted rate ratios of hospitalized MI and CVA events were then calculated. RESULTS: The adjusted rate ratio for MI was 2.50 (95% CI: 1.83-3.41, p < 0.001) for DME versus diabetes controls. Predictors of MI events were heart disease, history of acute MI, and prior use of antiplatelet or anticoagulant drugs. The adjusted rate ratio for CVA was 1.98 (95% CI: 1.39-2.83, p < 0.001) for DME versus diabetes controls. Predictors of CVA events were cardiac arrhythmia, Charlson comorbidity scores, history of CVA, hyperlipidemia, and other cerebrovascular diseases. CONCLUSION: Event rates of MI or CVA were higher in patients with DME than in diabetes controls. This study is one of few with sufficient sample size to accurately estimate the relationship between DME and cardiovascular outcomes.

Cost-effectiveness of ranibizumab in treatment of diabetic macular oedema (DME) causing visual impairment: evidence from the RESTORE trial.

BACKGROUND/AIMS: To evaluate the cost-effectiveness of ranibizumab as either monotherapy or combined with laser therapy, compared with laser monotherapy, in the treatment of diabetic macular oedema (DME) causing visual impairment from a UK healthcare payer perspective. METHODS: A Markov model simulated long-term outcomes and costs of treating DME in one eye (BCVA ≤75 letters) based on data from the RESTORE Phase III trial. Outcomes measured in quality-adjusted life-years (QALYs) were simulated for a 15-year time horizon based on 12-month follow-up from RESTORE and published long-term data. Costs included treatment, disease monitoring, visual impairment and blindness (at 2010 price levels). RESULTS: Ranibizumab monotherapy resulted in a 0.17 QALY gain at an incremental cost of £4191 relative to laser monotherapy, yielding an incremental cost-effectiveness ratio (ICER) of £24 028. Probabilistic sensitivity analysis showed a 64% probability of being cost-effective at a threshold of £30 000 per QALY. Combined ranibizumab and laser therapy resulted in a 0.13 QALY gain at an incremental cost of £4695 relative to laser monotherapy (ICER £36 106; 42% probability of ICER <£30 000). CONCLUSIONS: Based on RESTORE 1-year follow-up data, ranibizumab monotherapy appears to be cost-effective relative to laser monotherapy, the current standard of care. Cost-effectiveness of combination therapy is less certain. Ongoing studies will further inform on disease progression and the need for additional ranibizumab treatment.

Patterns of macular edema in patients with uveitis: qualitative and quantitative assessment using optical coherence tomography.

PURPOSE: To describe the morphologic characteristics of uveitic macular edema by the use of optical coherence tomography (OCT) and to investigate the correlation between tomographic features and visual acuity (VA). DESIGN: Cross-sectional study. PARTICIPANTS: Seventy consecutive patients with uveitis in a university-based practice with a clinical diagnosis of macular edema in at least one eye. Inclusion criteria were: (1) verification of macular edema by OCT, (2) adequate media clarity for fundus visualization, and (3) absence of coexisting ocular disease limiting visual potential. METHODS: Complete ophthalmic examination: best-corrected Snellen VA, slit-lamp examination, fundus biomicroscopy, indirect ophthalmoscopy, and OCT. Fluorescein angiography was performed in selected cases. MAIN OUTCOME MEASURES: Best-corrected Snellen VA and tomographic features of the macula, including macular thickness measurement and correlation of macular thickness with VA. RESULTS: Eighty-four eyes of 60 patients met the inclusion criteria. The mean VA (Snellen test) was 20/36. There were 3 patterns of macular edema: diffuse macular edema (DME), cystoid macular edema (CME), and serous retinal detachment (RD). Serous retinal detachment was detected in 17 eyes (20.2%). Patients were classified into the following groups: DME (46 eyes, 54.8%), CME (21 eyes, 25%), DME and RD (5 eyes, 5.9%), CME and RD (12 eyes, 14.3%). Epiretinal membrane was detected by OCT in 34 eyes (40.5%). Eight eyes (9.5%) demonstrated vitreomacular traction. The mean retinal thickness at the central fovea was 333+/-171 microm (mean +/- standard deviation). Macular edema was located mainly in the outer retinal layers. Eyes with CME had significantly greater retinal thickness measurements than eyes with DME (P<0.001). Multivariate analysis revealed that VA was negatively correlated with increased macular thickness, presence of CME, and RD (P<0.05). CONCLUSIONS: Optical coherence tomography demonstrated 3 patterns of macular edema in patients with uveitis: DME, CME, and RD. Epiretinal membrane coexisted in a significant percentage of patients. In patients with uveitis with clear media, the morphologic features of macular edema and macular thickness correlated with VA.

Quantitative assessment of retinal thickness in diabetic patients with and without clinically significant macular edema using optical coherence tomography.

PURPOSE: To assess patients with diabetic macular edema quantitatively using optical coherence tomography (OCT). METHODS: OCT was performed in 14 eyes with diabetic retinopathy and ophthalmoscopic evidence of clinically significant macular edema (CSME) and in 19 diabetic eyes without CSME. Retinal thickness was computed from the tomograms at fovea and other 36 locations throughout the macula. RESULTS: The mean +/- standard deviation foveal thickness was 255.6 +/- 138.9 microm in eyes with CSME, and 174.6 +/- 38.2 microm in eyes without CSME (p = 0.051). Within 2000 microm of the center of the macula, eyes with CSME had significantly thicker retina in the inferior quadrant than those without CSME (p < 0.01). The foveal thickness was correlated with logMAR visual acuity (gamma = 0.68, p < 0.01). OCT identified sponge-like retinal swelling and/or cystoid macular edema in 11 (58%) eyes without CSME, and in 12 (86%) eyes with CSME. CONCLUSIONS: Criteria of CSME seem to be insufficient in really identifying macular edema. OCT may be more sensitive than a clinical examination in assessing diabetic macular edema and is a quantitative tool for documenting changes in macular thickening.

Continuous computer simulation analysis of the cost-effectiveness of screening and treating diabetic retinopathy.

This paper analyzes the cost-effectiveness of screening and treating diabetic retinopathy (DR) by simulating the disease progress continuously with existing data. A new computer simulation based on Monte Carlo techniques and logistic transformation follows cohorts from diabetes onset until death in five care scenarios. For younger-onset patients, ophthalmic care reduces the prevalence of blindness by 52% or greater while savings in disability facilities and production losses surpass direct costs. For older-onset patients, less favorable results appear. Financial benefits surpass costs for juvenile-onset patients. For other patients, the net costs of ophthalmic care seem lower than in other health care programs.