Assessment of Serum Atherogenic Indices and Insulin Resistance in Retinal Vein Occlusion.

Objectives: This study aimed to investigate serum atherogenic indices as novel cardiovascular risk factors associated with retinal vein occlusion (RVO). Materials and Methods: This retrospective case-control study included 57 patients with newly diagnosed RVO whose plasma lipid profile (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol [TC], and triglycerides [TG]) and insulin resistance were examined. Serum atherogenic indices (LDL-C/HDL-C, TC/HDL-C, TG/HDL-C, and non-HDL-C/HDL-C ratios) and presence of insulin resistance were compared between the patients and 63 healthy subjects. Cut-off values were determined by receiver operating characteristic curve analysis. Results: The mean age of the RVO patients was 63.7±9.4 years. Plasma levels of LDL-C, HDL-C, TC, and TG showed no significant difference between the patient and control groups (p>0.05). However, LDL-C/HDL-C, non-HDL-C/HDL-C, and TC/HDL-C ratios were higher in the RVO group compared to healthy subjects (p=0.015, p=0.036, and p=0.015, respectively). Fasting insulin concentrations, plasma insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) index were higher in the RVO patients compared to controls (p=0.003, p=0.001, and p=0.001, respectively). Conclusion: LDL-C/HDL-C, TC/HDL-C, and non-HDL-C/HDL-C ratios were found to be increased in RVO. Compared to the traditional plasma lipid profile, serum atherogenic indices were found to be superior predictors of RVO development. Measurement of HOMA-IR index should be taken into consideration in the evaluation of insulin resistance. High serum atherogenic indexes in RVO patients reveal the need to take precautions against the risk of cardiovascular disease and stroke.

Assessment of systemic inflammatory response index and other inflammatory indicators in retinal vein occlusion.

Retinal vein occlusion (RVO) is the second most common retinal vascular disease after diabetic retinopathy. The study aimed to evaluate the association and the predictive value of inflammatory indicators in RVO. Sixty patients with RVO and 60 healthy individuals were enrolled in this retrospective study. Inflammatory indicators and other hematological parameters obtained from the peripheral venous sample were analyzed and compared among groups. White blood cell count (P = .003), neutrophil (P < .001), neutrophil-to-lymphocyte ratio (NLR) (P < .001), monocyte-to-lymphocyte ratio (MLR) (P < .001), platelet-to-lymphocyte ratio (PLR) (P = .014), systemic immune-inflammation index (SII) (P < .001), and systemic inflammatory response index (SIRI) (P < .001) were significantly higher; the lymphocyte count (P < .001) was significantly lower in patients with RVO. According to receiver operating characteristic analysis, NLR was significant at the good level (area under the curve [AUC] = 0.817, P < .001); SIRI, SII, and MLR were significant at the fair level (AUC = 0.774, P < .001; AUC = 0.733, P < .001, and AUC = 0.724, P < .001, respectively) and PLR (AUC = 0.630, P = .014) was significant at the weak level in terms of RVO prediction. SIRI was superior to other indicators, except NLR, to predict RVO. SIRI, NLR, SII, MLR, and PLR can be used as predictors for identifying the risk of RVO.

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.

Assessment of Systemic Immune-inflammation Index Levels in Patients with Retinal Vein Occlusion.

PURPOSE: To assess the predictive value of inflammatory markers calculated from complete blood counts in patients with retinal vein occlusion (RVO). METHODS: This was a retrospective cross-sectional study with a total of 56 RVO patients and 56 age- and gender-matched controls involved. All subjects went through a routine ocular examination, and the peripheral venous blood samples were collected to analyze the differences in inflammatory markers between groups. RESULTS: The systemic immune-inflammation index (SII) and neutrophil-to-lymphocyte ratio (NLR) values were significantly higher in RVO patients than those in the controls (p=0.002, p=0.004, respectively). According to the receiver operating characteristic (ROC) curve analysis, the areas under the curve (AUC) of SII was 0.666. The AUC of NLR was 0.657. CONCLUSION: As a novel inflammatory indicator, SII is a more promising indicator than NLR and PLR in the prediction of RVO development.

Quantitative Assessment Parameters of Peripapillary Regions with Branch Retinal Vein Occlusion by Using Optical Coherence Tomography Angiography.

Purpose: To investigate the baseline parameters of peripapillary regions in both eyes of patients with unilateral branch retinal vein occlusion (BRVO) using optical coherence tomography angiography (OCTA) and their association with best-corrected visual acuity (BCVA). Methods: Forty-eight unilateral BRVO patients were enrolled. The 4.5 × 4.5 mm disc angiogram was acquired in the BRVO eyes and fellow eyes using the OCTA. Radial peripapillary capillary (RPC), whole vessel density, and retinal nerve fiber layer (RNFL) thickness in different regions and optic nerve head (ONH) analysis were automatically calculated. The partition includes the whole image, peripapillary, superior hemifield, inferior hemifield, eight equally divided sectors, and nine evenly divided square areas. Results: All vessel density and capillary vessel density in the whole and peripapillary regions of BRVO eyes were significantly lower than those in fellow eyes. The RNFL peripapillary thickness in BRVO eyes was significantly higher than those in fellow eyes. In eyes with supertemporal vein occlusion, all vessel density both in the superior hemifield and in the G12 region was significantly reduced compared with that in the fellow eyes. The capillary vessel density was significantly lower in the superior hemifield, superior temporal (ST), superior nasal (SN), and temporal superior (TS) areas than in the fellow eyes. The RNFL thickness in the NI, IN, TI, and TS sectors was significantly higher than in fellow eyes (all P < 0.05). Conclusions: OCTA provided quantitative information on peripapillary vascular density and RNFL thickness changes in BRVO. Branch retinal vein occlusion not only affects the blood vessel density in the macular area but also decreases the radial peripapillary capillaries. The capillary density is mainly affected in the affected hemifield but not in the unaffected hemifield.

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.

Assessment of intravitreal anti-VEGF drugs and dexamethasone for retinal diseases in real world setting: A multi-centre prospective study from Southern Italy.

Describe drug utilisation and clinical outcomes of intravitreal anti-VEGF drug and dexamethasone use in the real-world setting in Southern Italy using data from multi-centre study of retinal disease. Clinical data of retinal disease patients treated with anti-VEGF drugs and dexamethasone implant in 6 out-patient ophthalmology centres from Southern Italy were collected by means of an electronic case report form. Patients receiving at least one intravitreal injection/implant of the study drugs were followed for up to two years and described in terms of demographics and clinical characteristics. Drug utilisation patterns were described. A sign-rank test was used to compare clinical data on visual acuity and other ophthalmic parameters from baseline at different follow-up times for each indication. Data from 1327 patients was collected. Most patients were diagnosed with age-related macular degeneration (AMD) (660, 49.7%), followed by diabetic macular oedema (423, 31.9%), retinal vein occlusion (164, 12.3%), and myopic choroidal neovascularization (80, 6.0%). Patients were followed for a median of 10.3 months (interquartile range: 3.6 - 24.7 months). Mean patient age was 69.7 (±10.9) years and 54.2% were males. Ranibizumab (55.4%) and aflibercept (27.5%) were the most commonly used drugs. Baseline visual acuity significantly improved by about 0.05 to 0.1 logMAR at all follow-up times for AMD and RVO but less consistently for the other diseases. Intravitreal ranibizumab use accounted for half of all treatment for retinal diseases in a Southern Italian out-patient setting. Patients treated with anti-VEGF drugs for AMD and RVO in Southern Italy experienced significant improvement in VA.

Assessment of Red Cell Distribution Width, Platelet/lymphocyte Ratio, Systemic Immune-inflammation Index, and Neutrophil/lymphocyte Ratio Values in Patients with Central Retinal Artery Occlusion.

PURPOSE: To evaluate complete blood count (CBC)-derived inflammatory indices in central retinal artery occlusion (CRAO). METHODS: A total of 42 patients with CRAO (CRAO group) and 42 age- and sex-matched subjects without CRAO (Control group) were included. CBC parameters including red cell distribution width (RDW) levels were assayed. Platelet/lymphocyte ratio (PLR), systemic immune-inflammation index (SII) and neutrophil/ lymphocyte ratio (NLR) were calculated. RESULTS: RDW, PLR, SII and NLR values were significantly higher in CRAO group than control group [15.2 ± 1.47% vs 13.96 ± 1.13% (p < .001), 127.94 ± 48.21 vs 101.16 ± 24.84 (p = .008), 667.11 ± 357.84 vs 493.44 ± 207.07 (p = .008), 2.70 ± 1.27 vs 2.13 ± 0.83 (p = .018), respectively]. In multivariate analysis only RDW was independent predictor for CRAO (OR 2.317, p < .001). On ROC analysis, area under curve of RDW, PLR, SII, and NLR for CRAO were 0.761, 0.685, 0.622 and 0.618, respectively. CONCLUSION: RDW seems superior to other inflammatory indices to predict CRAO.

Anterior chamber changes assessment by Scheimpflug analysis after intravitreal dexamethasone implantation.

PURPOSE: To evaluate structural changes in the anterior chamber and intraocular pressure (IOP) changes following intravitreal dexamethasone implantation. METHODS: Forty-two eyes of 42 patients that received intravitreal dexamethasone implant for the management of macular edema secondary to diabetic retinopathy or branch retinal vein occlusion (BRVO) were included in the study. IOP was measured by Goldmann applanation tonometry. Anterior chamber depth (ACD) and iridocorneal angle (ICA) was measured by a Scheimflug camera (Sirius, CSO, Italy) the day before the injection of the dexamethasone implant and on postoperative day 1, first week, and first month. RESULTS: Mean IOP was 15.14 ± 2.77 mmHg before the procedure and, 15.67 ± 3.70 mmHg, 15.86 ± 3.11 mmHg, 16.21 ± 2.75 mmHg on day 1, first week, and first month following intravitreal dexamethasone implantation, respectively. Mean ICA and ACD were significantly higher in pseudophakic eyes compared to phakic eyes. However, there was no statistically significant change in ICA before and after the procedure (on postoperative day 1, first week, and first month) among both phakic and pseudophakic patients (p = 0.783). Similarly, ACD remained unchanged after the procedure (on postoperative day 1, first week, and first month) compared to the initial measurement (p = 0.802). CONCLUSION: This study confirmed that there was an increase in IOP. However, these changes were not accompanied with a change in ACD or ICA.

Intravitreal ranibizumab versus aflibercept versus bevacizumab for macular oedema due to central retinal vein occlusion: the LEAVO non-inferiority three-arm RCT.

BACKGROUND: Licensed ranibizumab (0.5 mg/0.05 ml Lucentis®; Novartis International AG, Basel, Switzerland) and aflibercept (2 mg/0.05 ml Eylea®; Bayer AG, Leverkusen, Germany) and unlicensed bevacizumab (1.25 mg/0.05 ml Avastin®; F. Hoffmann-La Roche AG, Basel, Switzerland) are used to treat macula oedema due to central retinal vein occlusion, but their relative clinical effectiveness, cost-effectiveness and impact on the UK NHS and Personal Social Services have never been directly compared over the typical disease treatment period. OBJECTIVE: The objective was to compare the clinical effectiveness and cost-effectiveness of three intravitreal antivascular endothelial growth factor agents for the management of macula oedema due to central retinal vein occlusion. DESIGN: This was a three-arm, double-masked, randomised controlled non-inferiority trial. SETTING: The trial was set in 44 UK NHS ophthalmology departments, between 2014 and 2018. PARTICIPANTS: A total of 463 patients with visual impairment due to macula oedema secondary to central retinal vein occlusion were included in the trial. INTERVENTIONS: The participants were treated with repeated intravitreal injections of ranibizumab (n = 155), aflibercept (n = 154) or bevacizumab (n = 154). MAIN OUTCOME MEASURES: The primary outcome was an increase in the best corrected visual acuity letter score from baseline to 100 weeks in the trial eye. The null hypothesis that aflibercept and bevacizumab are each inferior to ranibizumab was tested with a non-inferiority margin of -5 visual acuity letters over 100 weeks. Secondary outcomes included additional visual acuity, and imaging outcomes, Visual Function Questionnaire-25, EuroQol-5 Dimensions with and without a vision bolt-on, and drug side effects. Cost-effectiveness was estimated using treatment costs and Visual Function Questionnaire-Utility Index to measure quality-adjusted life-years. RESULTS: The adjusted mean changes at 100 weeks in the best corrected visual acuity letter scores were as follows - ranibizumab, 12.5 letters (standard deviation 21.1 letters); aflibercept, 15.1 letters (standard deviation 18.7 letters); and bevacizumab, 9.8 letters (standard deviation 21.4 letters). Aflibercept was non-inferior to ranibizumab in the intention-to-treat population (adjusted mean best corrected visual acuity difference 2.23 letters, 95% confidence interval -2.17 to 6.63 letters; p = 0.0006), but not superior. The study was unable to demonstrate that bevacizumab was non-inferior to ranibizumab in the intention-to-treat population (adjusted mean best corrected visual acuity difference -1.73 letters, 95% confidence interval -6.12 to 2.67 letters; p = 0.071). A post hoc analysis was unable to demonstrate that bevacizumab was non-inferior to aflibercept in the intention-to-treat population (adjusted mean best corrected visual acuity difference was -3.96 letters, 95% confidence interval -8.34 to 0.42 letters; p = 0.32). All per-protocol population results were the same. Fewer injections were required with aflibercept (10.0) than with ranibizumab (11.8) (difference in means -1.8, 95% confidence interval -2.9 to -0.8). A post hoc analysis showed that more bevacizumab than aflibercept injections were required (difference in means 1.6, 95% confidence interval 0.5 to 2.7). There were no new safety concerns. The model- and trial-based cost-effectiveness analyses estimated that bevacizumab was the most cost-effective treatment at a threshold of £20,000-30,000 per quality-adjusted life-year. LIMITATIONS: The comparison of aflibercept and bevacizumab was a post hoc analysis. CONCLUSION: The study showed aflibercept to be non-inferior to ranibizumab. However, the possibility that bevacizumab is worse than ranibizumab and aflibercept by 5 visual acuity letters cannot be ruled out. Bevacizumab is an economically attractive treatment alternative and would lead to substantial cost savings to the NHS and other health-care systems. However, uncertainty about its relative effectiveness should be discussed comprehensively with patients, their representatives and funders before treatment is considered. FUTURE WORK: To obtain extensive patient feedback and discuss with all stakeholders future bevacizumab NHS use. TRIAL REGISTRATION: Current Controlled Trials ISRCTN13623634. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 38. See the NIHR Journals Library website for further project information.

The eye functions like a camera. The retina, at the back of the eye, is the camera film, and the centre, the macula, allows us to see fine details. Approximately 6500 people each year in England and Wales are affected by fluid leaking out of congested tiny blood vessels, causing macular swelling or oedema. The cause is blockage of the main vein that normally drains blood from the retina. Three drugs, injected into the eye in tiny amounts every 4­8 weeks, have been shown to improve the vision of people with this condition. Two drugs, ranibizumab (0.5 mg/0.05 ml Lucentis^®; Novartis International AG, Basel, Switzerland) and aflibercept (2 mg/0.05 ml Eylea^®; Bayer AG, Leverkusen, Germany), are licensed for UK use, but the third, bevacizumab (1.25 mg/0.05 ml Avastin^®; F. Hoffmann-La Roche AG, Basel, Switzerland), is not, even though it is much cheaper and used extensively worldwide. To our knowledge, no trials have compared the three drugs over the typical 2-year treatment period. This multicentre, Phase III, double-masked, randomised controlled non-inferiority trial comparing the clinical effectiveness and cost-effectiveness of intravitreal therapy with ranibizumab (Lucentis) versus aflibercept (Eylea) versus bevacizumab (Avastin) for macular oedema due to central retinal Vein Occlusion (LEAVO) was designed to compare ranibizumab, aflibercept and bevacizumab in this type of macular oedema. The trial showed that all three drugs improved vision a lot, but bevacizumab improved vision to a slightly lesser degree than the other two drugs. All patients should be aware of these findings before considering their treatment options. A comparison of the costs and benefits of ranibizumab, aflibercept and bevacizumab, using data from the trial and other sources, found that all three led to similar improvements in quality of life. Because aflibercept and ranibizumab are so much more expensive, they may be poor value for money. If patients, their representatives and funders all agree, it may be possible to treat this type of macular oedema with bevacizumab, which is cheaper, keeping the other agents available if needed.

Estrategia de superación para el mejoramiento del desempeño profesional de oftalmólogos de la Atención Primaria de Salud en Santiago de Cuba / Training strategy for improving the professional performance in primary health care ophthalmologists in Santiago de Cuba

El vertiginoso desarrollo científico - tecnológico de la oftalmología requiere de una actualización sistemática desde el punto de vista teórico - práctico. A tales efectos, se diseñó una estrategia de superación para el mejoramiento del desempeño profesional de los oftalmólogos de la Atención Primaria de Salud dirigida a la atención integral de los pacientes con oclusiones vasculares retinianas. Se emplearon métodos de los niveles teórico y empírico. Fue diseñada en 4 etapas y se utilizó el ciclo Deming como referente metodológico. Se establecieron relaciones esenciales que ofrecen coherencia lógica interna a la educación médica en su concepción como ciencia en construcción, en particular en el área de la formación permanente y continuada de los profesionales de la salud, al profundizar en el orden conceptual, metodológico y epistemológico en los procesos de desempeño profesional y superación.

The fast scientific and technological development of Ophthalmology requires a systematic updating from the theoretical and practical points of view. To such effects, a training strategy was designed for the improvement of professional performance of the primary care ophthalmologists directed to the comprehensive care of patients with retinal vascular occlusions. Empiric and theoretical level methods were used. The strategy was designed in 4 stages and the Deming cycle was implemented as methodological referent. Essential relationships were established which offer internal logical coherence to the Medical Education in its conception as science, particularly in the area of permanent and continued training of the health professionals, as there is a deepening in the conceptual, methodological and epistemological order in the processes of professional and training performance.

Cost-effectiveness analysis of ranibizumab for retinal vein occlusion patients in China from the societal perspective.

BACKGROUND: Clinical trials in China have demonstrated that ranibizumab can improve the clinical outcomes of branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO). However, no economic evaluation of ranibizumab has been conducted among Chinese patient population. METHODS: To provide insights into the economic profile of ranibizumab among Chinese RVO population, a Markov state-transition model was used to predict the outcomes of ranibizumab comparing to laser photocoagulation and observational-only care from the societal perspective. This model simulated changes in patient visuality, quality-adjusted of life years (QALY), medical costs, and direct non-medical costs of individuals with visual impairment due to BRVO or CRVO in lifetime. The base-case analysis used an annual discount rate of 5% for costs and benefits following the China Guidelines for Pharmacoeconomic Evaluations. Deterministic and probabilistic sensitivity analyses were performed to test the robustness of the model. RESULTS: The base-case incremental cost-effectiveness ratio (ICER) comparing ranibizumab to laser photocoagulation was ¥65,008/QALY among BRVO patients and was ¥65,815/QALY among CRVO patients, respectively. Comparing to the 2019 gross domestic product (GDP) per capita of ¥71,000, both two ICERs were far below the cost-effective threshold at three times of GDP per capita (¥213,000). The deterministic and probabilistic sensitivity analyses demonstrated the base-case results were robust in most of the simulation scenarios. CONCLUSION: The current Markov model demonstrated that ranibizumab may be cost-effective compared with laser photocoagulation to treat BRVO and cost-effective compared to observation-only care to treat CRVO in China from the societal perspective.

Cost Effectiveness of Ranibizumab vs Aflibercept vs Bevacizumab for the Treatment of Macular Oedema Due to Central Retinal Vein Occlusion: The LEAVO Study.

BACKGROUND: We aimed to assess the cost effectiveness of intravitreal ranibizumab (Lucentis), aflibercept (Eylea) and bevacizumab (Avastin) for the treatment of macular oedema due to central retinal vein occlusion. METHODS: We calculated costs and quality-adjusted life-years from the UK National Health Service and Personal Social Services perspective. We performed a within-trial analysis using the efficacy, safety, resource use and health utility data from a randomised controlled trial (LEAVO) over 100 weeks. We built a discrete event simulation to model long-term outcomes. We estimated utilities using the Visual-Functioning Questionnaire-Utility Index, EQ-5D and EQ-5D with an additional vision question. We used standard UK costs sources for 2018/19 and a cost of £28 per bevacizumab injection. We discounted costs and quality-adjusted life-years at 3.5% annually. RESULTS: Bevacizumab was the least costly intervention followed by ranibizumab and aflibercept in both the within-trial analysis (bevacizumab: £6292, ranibizumab: £13,014, aflibercept: £14,328) and long-term model (bevacizumab: £18,353, ranibizumab: £30,226, aflibercept: £35,026). Although LEAVO did not demonstrate bevacizumab to be non-inferior for the visual acuity primary outcome, the three interventions generated similar quality-adjusted life-years in both analyses. Bevacizumab was always the most cost-effective intervention at a threshold of £30,000 per quality-adjusted life-year, even using the list price of £243 per injection. CONCLUSIONS: Wider adoption of bevacizumab for the treatment of macular oedema due to central retinal vein occlusion could result in substantial savings to healthcare systems and deliver similar health-related quality of life. However, patients, funders and ophthalmologists should be fully aware that LEAVO could not demonstrate that bevacizumab is non-inferior to the licensed agents.

Factors Associated With a Patient's Decision to Select a Cost-effective vs the Most Effective Therapy for Their Own Eye Disease.

Importance: Ten percent of the Medicare Part B budget is spent on aflibercept, used to treat a myriad of ocular neovascular diseases. A substantial portion of these costs can be attributed to a few hundred ophthalmologists, raising concerns regarding the influence of pharmaceutical companies on the choice of medication by a relatively small group of clinicians. One approach to protect patients' health care interests is to include them in deliberations on the choice of therapy for their eye disease. Objective: To examine factors associated with patients' choice between an effective and less expensive off-label drug or a more effective, but also more expensive, US Food and Drug Administration (FDA)-approved drug. Design, Setting, and Participants: This retrospective cohort analysis used data from the satellite office of a tertiary referral center from August 2, 2013, to April 9, 2018. Insured patients initiating treatment with anti-vascular endothelial growth factor were included in the analysis. Data were analyzed from March 26, 2018, to June 10, 2020. Interventions: Patients were asked to choose between bevacizumab (approximately $100 per dose), a chemotherapy that is effective, but not FDA approved, for the treatment of ocular vascular disease, or aflibercept (approximately $2000 per dose), an FDA-approved drug for ocular vascular disease that may be more effective than bevacizumab in some patients. Independent of this choice, patients were separately asked by a study coordinator to participate in an invasive clinical study for which they would not be compensated, there was a small risk for an adverse event, and they would not personally benefit from participating (a surrogate marker for altruism). Main Outcomes and Measures: Factors associated with patients' choice of medication, including age, sex, ocular disease, race, and participation in an invasive clinical study. Results: A total of 189 patients were included in the analysis (106 women [56%]; mean [SEM] age, 74.6 [0.8] years). Despite being told that it may not be as effective as aflibercept, 100 patients (53%) selected bevacizumab for their own eye care. An act of altruism (ie, participation in an invasive clinical study) when the patient was making a choice between the 2 drugs was associated with a patient's choice of bevacizumab (odds ratio [OR], 7.03; 95% CI, 2.27-21.80; P < .001); the OR for selecting bevacizumab for patients who never agreed to participate in the clinical study was 0.45 (95% CI, 0.25-0.83; P = .001). Age (OR, 1.00; 95% CI, 0.97-1.03; P = .86), race (OR, 0.70; 95% CI, 0.41-1.22; P = .21), sex (OR, 0.72; 95% CI, 0.39-1.35; P = .31), presence of diabetes (OR, 1.52; 95% CI, 0.59-3.93; P = .39), and type of eye disease (OR, 0.56; 95% CI, 0.30-1.04; P = .07) were not associated with choice of therapy. Conclusions and Relevance: These findings suggest that clinicians must consider the ethical implications of the influence of altruism when patients participate in the decision between cost-effective vs the most effective medicines for their own health care.

ASSESSMENT OF HYPERREFLECTIVE FOCI AFTER BEVACIZUMAB OR DEXAMETHASONE TREATMENT ACCORDING TO DURATION OF MACULAR EDEMA IN PATIENTS WITH BRANCH RETINAL VEIN OCCLUSION.

PURPOSE: To evaluate the association between hyperreflective foci (HRF) on spectral domain optical coherence tomography and therapeutic effect of intravitreal bevacizumab (IVB) or intravitreal dexamethasone implants (IVD) according to macular edema (ME) duration in branch retinal vein occlusion. METHODS: Consecutive treatment-naive patients received IVB or IVD for at least 6 months. Each group was subdivided according to ME duration (<3 months vs. ≥3 months). Hyperreflective foci and best-corrected visual acuity were compared. RESULTS: Of 139 eyes (139 patients), 69 received IVB and 70 received IVD. At baseline, eyes with ME ≥ 3 months had more outer and total retinal HRF than eyes with ME < 3 months (P < 0.001 and P = 0.001). At 6 months, the IVD group exhibited a greater reduction in outer retinal HRF than the IVB group in both ME duration subgroups (P = 0.015 and P < 0.001). In the ME ≥ 3 months group, IVD resulted in greater best-corrected visual acuity improvement than IVB (P = 0.017). CONCLUSION: Increased outer retinal HRF at baseline in eyes with ME ≥ 3 months together with a greater reduction in HRF at 6 months and better visual outcomes after IVD suggests that the inflammatory aspect of disease should be considered in the treatment of ME. Thus, IVD injection could be more appropriate for patients with a longer ME duration after branch retinal vein occlusion.

Predictive values of initial semi-quantitative assessment of relative afferent pupillary defect for neovascularization in central retinal vein occlusion.

PURPOSE: To measure the predictive values of relative afferent pupillary defect (RAPD) assessed semi-quantitatively, and visual acuity (VA) at onset of central retinal vein occlusion (CRVO), for neovascularization. METHODS: Retrospective analysis of the TROXHEMO trial that included patients with CRVO within 30 days after the onset. Inclusion criteria were as follows: semi-quantitative RAPD assessment at diagnosis and/or at one month. RAPD was 'severe' if ≥ 0.9 log. Exclusion criteria were as follows: prophylactic panretinal photocoagulation (PRP) before neovascularization. RESULTS: Among the 119 patients enrolled in the main centre, 101 were analysed. 26 had a neovascular complication during the twelve months of follow-up: rubeosis (19), glaucoma (7) and posterior neovascularization (15). The mean time to onset of a neovascular complication was 4.7 months (1 to 12, median 3 months). All the patients who had a neovascular complication had RAPD at first examination or at one month (negative predictive value (NPV) = 100%) but the positive predictive value (PPV) was low (31%, 95% CI [21%; 42%]). The association 'severe RAPD or VA < 35 letters (ETDRS) at inclusion or at one month' was the best compromise between PPV (53%, [39%; 68%]) and NPV (96%, [92%; 100%]). CONCLUSION: To predict neovascularization, RAPD should be routinely evaluated with filters: the risk of neovascular complication is (a) almost nil if there is no RAPD, (b) very low if there is no severe RAPD and if VA is higher than 35 letters, and (c) higher than 50% if RAPD is ≥ 0.9 log or if VA is less than 35 letters.

NONPERFUSION ASSESSMENT IN RETINAL VEIN OCCLUSION: Comparison Between Ultra-widefield Fluorescein Angiography and Widefield Optical Coherence Tomography Angiography.

PURPOSE: To compare widefield optical coherence tomography angiography (OCTA) to ultra-widefield fluorescein angiography (UWFA) in the assessment of nonperfusion in retinal vein occlusion (RVO). METHODS: A cross-sectional study of 43 eyes of 43 patients with RVO examined using both widefield OCTA (PLEX Elite, Carl Zeiss Meditec, Dublin, CA) with a panoramic montage of five 12 × 12-mm images and UWFA (Optos, 200°). Qualitative analysis was performed according to nonperfusion areas (cutoff: three disk areas) on widefield OCTA. The quantitative analysis assessed the vascular density on the widefield OCTA and ischemic index on UWFA. RESULTS: The ischemic index on UWFA and vascular density in the superficial and deep plexus correlated significantly (P = 0.019, r = 0.357 and P < 0.013, r = 0.375, respectively). The qualitative classification on widefield OCTA and ischemic index on UWFA correlated significantly (P < 0.001, r = 0.618). For the detection of marked nonperfusion (ischemic index ≥ 25%), widefield OCTA had a sensitivity of 100% and a specificity of 64.9%. CONCLUSION: The presence of nonperfusion on UWFA correlated with widefield OCTA. Optical coherence tomography angiography could help to identify high-risk RVO patients who might benefit from a further evaluation using fluorescein angiography.

Assessment of pupillary light reflex using dynamic pupillometry in laser-treated eyes with retinal vein occlusion.

PURPOSE: This study aims to evaluate the pupillary light reflex measured with dynamic pupillometry in patients who underwent retinal laser photocoagulation due to unilateral retinal vein occlusion (RVO). METHODS: A total of 48 patients with unilateral RVO were included in the study. Thirty-four patients had undergone retinal laser photocoagulation while the remaining 14 patients that did not undergo laser treatment were observed for control purposes. Of the laser-treated eyes, 14 eyes (41.2%) had central RVO (CRVO) and 20 eyes (58.8%) had branch RVO (BRVO). Among the 14 patients with RVO without laser treatment, nine eyes (64.3%) had CRVO and five eyes (35.7%) had BRVO. Pupillary light reflexes were assessed with dynamic pupillometry (MonPackOne®; Metrovision, France). The parameters of the eyes with RVO were compared with that of fellow healthy eyes. RESULTS: Mean patient age was 65.8 ± 10.4 years and median time after photocoagulation was 25.5 months. Eyes that received laser photocoagulation had lower pupil contraction amplitude (p = 0.037), prolonged contraction latency (p = 0.027), slower contraction velocity (p = 0.043), and slower dilation velocity (p < 0.001) compared to healthy fellow eyes. Subgroup analysis revealed that eyes with CRVO had lower contraction amplitude (p = 0.013) and slower dilation velocity (p = 0.003), and eyes with BRVO had slower dilation velocity (p = 0.003). Non-laser-treated eyes with RVO revealed no significant difference in any of the pupillary light reflex parameters compared to fellow eyes. CONCLUSION: Laser-treated eyes with RVO demonstrated changes in pupillary light reflex parameters including reduced contraction amplitude, prolonged contraction latency, and slower contraction and dilation velocities measured with dynamic pupillometry.

Cost-Utility of Anti-Vascular Endothelial Growth Factor Treatment for Macular Edema Secondary to Central Retinal Vein Occlusion.

PURPOSE: To evaluate the cost-utility of treatment for macular edema in central retinal vein occlusion (CRVO) using intravitreal injections of the anti-vascular endothelial growth factor (VEGF) agents bevacizumab, ranibizumab, and aflibercept. DESIGN: Decision analysis model of cost-utility. PARTICIPANTS: Data from study participants in the Lucentis, Eylea, Avastin in Vein Occlusion (LEAVO) study. METHODS: A decision analysis of a disease simulation model was used to calculate comparative cost-utility of intravitreal bevacizumab (IVB), intravitreal ranibizumab (IVR), and intravitreal aflibercept (IVA) for the treatment of macular edema associated with CRVO based on data from the LEAVO study. Center for Medicare and Medicaid Services data were used to calculate associated modeled costs in a hospital- or facility-based and nonfacility setting from a third-party payer perspective, and societal costs also were calculated. Cost utility was calculated based on the preserved visual utility during the 2 years of the study and also by estimating utility for the expected lifetime. MAIN OUTCOME MEASURES: Cost of treatment, cost per quality-adjusted life-year (QALY), and incremental cost-effectiveness ratio (ICER). RESULTS: From the third-party payer perspective, the estimated lifetime costs per QALY in the facility and nonfacility settings were $39 325 and $17 944, respectively, for IVB; $114 095 and $92 653, respectively, for IVR; and $78 935 and $63 270, respectively, for IVA. From the societal perspective, the estimated lifetime costs per QALY in the facility setting were $52 754 for IVB, $128 242 for IVR, and $86 262 for IVA. The ICER of IVA compared with that of IVB was $153 633/QALY from the third-party facility setting and $152 992/QALY from the societal perspective. The use of IVB compared with IVR and IVA compared with IVR were cost-saving interventions (ICER, <0) regardless of the perspective or setting. CONCLUSIONS: In the treatment of macular edema in CRVO, IVB yields the best cost utility among the 3 anti-VEGF agents modeled. Intravitreal aflibercept maintains acceptable lifetime cost per QALY while having a favorable cost utility compared with IVR.