Cost-consequence analysis of extended loading dose of anti-VEGF treatment in diabetic macular edema patients.

BACKGROUND: The DRCR.net Protocol T clinical trial assessed the comparative efficacy and safety of anti-VEGF treatments including aflibercept, ranibizumab and bevacizumab in diabetic macular edema (DME). Post -hoc analyses showed that after a 12-week induction period, there was still DME resolution in an increasing number of patients through week 24. PURPOSE: To assess clinical and cost consequences of extending the anti-VEGF loading dose from 3 to 6 monthly injections in patients with persistent DME in Spain. METHODS: From a hospital pharmacy perspective, a cost-consequence analysis model was developed to estimate the incremental cost needed to obtain an additional response at month 6. To estimate drug treatment costs, ex-factory prices (€, 2019) were considered for aflibercept, ranibizumab and bevacizumab. Response/nonresponse rates at 3/6 months were obtained from the Protocol T 24-week post hoc analysis (n = 546). Persistent DME was present in 50.8 and 31.6% of the 190 aflibercept-treated patients at month 3 and month 6, respectively. Of the 176 ranibizumab- and 180 bevacizumab-treated patients, 53.2 and 72.9%, respectively, had persistent DME at month 3, and 41.5 and 65.6%, respectively, had persistent DME at month 6. Sensitivity analysis considered the split of bevacizumab vials. RESULTS: Extending the loading dose in nonresponder patients would cost €214,862.57, €208,488.98 and €134,483.16 to obtain 37, 21 and 13 additional aflibercept, ranibizumab and bevacizumab responder patients, respectively. The total number of extended injections (months 3-6) used in patients with persistent DME at month 6 was 180, 219 and 354 for aflibercept, ranibizumab and bevacizumab, respectively. CONCLUSIONS: To extend the anti-VEGF loading dose from 3 to 6 injections necessitates investing €5882.77 (8 injections), €10,091.03 (14 injections) and €10,198.59 (30 injections) per additional responder patient (3-month nonresponders and 6-month responders) to aflibercept, ranibizumab and bevacizumab, respectively. For the total of patients treated, on average €7927.02 (14 injections) per additional responder patient would be needed.

Open angle glaucoma secondary to endogenous cortisone due to pituitary microadenoma in a young patient, a case report. / Glaucoma de ángulo abierto secundario a cortisona endógena por microadenoma hipofisario en un paciente joven, a propósito de un caso.

CASE REPORT: A 31-year-old male was referred for evaluation after being diagnosed with Cushing syndrome secondary to a pituitary microadenoma. He presented with a reduced visual acuity and high intraocular pressure (IOP) of 48mmHg in both eyes. The examination with biomicroscopy showed normal anterior segment, increased cup to disc ratio, and open angle. There was a moderate-advanced involvement in the visual field. The patient was diagnosed with glaucoma secondary to endogenous corticosteroids, and medical treatment was initiated pending the removal of the adenoma. The IOP did not return to normal after the incomplete removal of the adenoma, so a trabeculectomy was performed to control the IOP. As conclusions: In the case of an ocular hypertension with pituitary tumour, secondary glaucoma to endogenous cortisone should be suspected. Early treatment of the tumour is necessary to bring the cortisone and IOP levels back to normal. Late diagnosis or incomplete treatment of these tumours may lead to not obtaining adequate IOP control.

Ocular hypertension as a cause of cilioretinal artery obstruction in the young patient, about a case. / Hipertensión ocular como causa de obstrucción de arteria ciliorretiniana en el paciente joven, a propósito de un caso.

CLINICAL CASE: A 16-year-old patient seen in the Emergency Department due to loss of visual acuity (VA) in the left eye (LE), and oppressive headache of 1 day onset. The patient was on treatment with topical corticosteroids for viral conjunctivitis. The VA was 1.00 in the right eye and 0.05 in LE. The intraocular pressure was 42mmHg in both eyes. In the LE, the funduscopy revealed retinal ischaemic oedema in the papillomacular bundle. The optical coherence tomography angiography (OCT-A) showed an obstruction of the cilioretinal artery. The systemic study was normal, the cardiac and supra-aortic trunks ultrasound was normal, with ocular hypertension secondary to corticosteroids being the only causative agent identified. This case shows that in the event of an obstruction of the cilioretinal artery, a systemic study should be performed in order to identify possible embolic phenomena. Ocular hypertension is one of the possible causes that may be responsible for this condition.

Agreement between Fourier-domain and swept-source optical coherence tomography used for optic nerve head measurements.

PURPOSE: To assess the correlation between optic nerve head measurements generated by Fourier-domain (FD) and swept-source (SS) optical coherence tomography (OCT) both in healthy Caucasian subjects and patients with primary open angle glaucoma (POAG). MATERIALS AND METHODS: This was a cross-sectional study of the right eyes of 118 subjects. In each participant, the measurements of disc area, cup to disc ratio (CDR), vertical cup to disc ratio (VCDR), rim area and rim volume were performed consecutively by FD-OCT and then SS-OCT. Participant age, gender and spherical equivalent were also recorded. Agreement between the two devices was assessed through intraclass correlation coefficients (ICC) and Bland-Altman plots. RESULTS: The study sample consisted of 95 healthy eyes and 23 eyes with glaucoma. Mean participant age was 48.6±20.0 years, 54.2% were female, and mean spherical equivalent was -1.6±3.0 diopters. FD-OCT and SS-OCT measurements were respectively: mean disc area 1.79±0.3 vs 1.83±0.3 mm2 (ICC=0.71), mean CDR 0.38±0.2 vs 0.33±0.2 (ICC=0.91), mean VCDR 0.58±0.2 vs 0.52±0.2 (ICC=0.92), mean rim area 1.05±0.4mm2 vs 1.03±0.5mm2 (ICC=0.29), and mean rim volume 0.14±0.11 vs 0.21±0.17mm3 (ICC=0.53). Good agreement between the devices was noted for rim area and rim volume in glaucoma subjects (ICC=0.76 and 0.68 respectively), while weak agreement was observed for these variables in healthy subjects (ICC≤0.50). CONCLUSIONS: The CDR and VCDR measurements provided by FD and SS OCT showed excellent agreement for the overall sample. When the devices were used for rim measurements, agreement was excellent only in the POAG patients.

Management of Wet Age-Related Macular Degeneration in Spain: Challenges for Treat and Extend Implementation in Routine Clinical Practice.

PURPOSE: To ascertain wet AMD (wAMD) management patterns in Spain. METHODS: A two-round Delphi study conducted through a questionnaire-based survey designed from literature review and validated by an independent Steering Committee. RESULTS: Forty-nine retina specialists experienced in wAMD participated by answering the two-round study questionnaire. Retina specialists are the main responsible for wAMD diagnosis and monitoring, including visits and associated procedures, with a median time per visit of 15 minutes. Standard treatment strategies are based on anti-VEGF administration, including standard loading dose administration followed by maintenance with aflibercept or ranibizumab (81% of patients). Although treat and extend (T&E) dosing strategy is considered as optimal for wAMD management (78% of the panelists), the main routine healthcare limitations (i.e., visits overload, reduced staff, short visit time, coordination issues, lack of facilities) conduct to self-defined "flexible" strategies, based on T&E and pro-re-nata (PRN) protocols. CONCLUSION: Proactive treatment patterns (T&E) are the preferred ones by the retina specialists in Spain. However, their proper implementation is difficult due to healthcare resource limitations, as well as organisation and logistic issues. The use of anti-VEGF agents with longer duration of action could facilitate the use of strict T&E approaches according to routine clinical practices.

Update on the usefulness of optical coherence tomography in assessing the iridocorneal angle. / Actualización de la utilidad de la tomografía de coherencia óptica para el estudio del ángulo iridocorneal.

The iridocorneal angle, due to its implications in the physiopathology of aqueous humour drainage, is a fundamental structure of the anterior chamber. Anterior segment optical coherence tomography is a rapid and non-invasive technique that obtains images in vivo. The high resolution allows it to analyse the normal anatomy of the angle, any alterations, and the changes that occur after different therapeutic interventions. Anterior segment optical coherence tomography technology has evolved to provide images that allow the identification and quantification of the angular structures in healthy subjects and in glaucoma patients, and especially the trabecular meshwork and the Schlemm's canal. It also enables the angle width to be quantified, with some objective parameters that have been standardised in recent years, such as the trabecular-iris angle, the angle opening distance, and the trabecular-iris area. This technique has multiple uses in the study of the different mechanisms of angle closure, the evaluation of changes after a laser peripheral iridotomy or iridoplasty after cataract surgery, as well as after the implantation of phakic lenses.

Update of choroidal imaging techniques: Past, present and future. / Actualización en técnicas de imagen coroidea: pasado, presente y futuro.

The choroid is the middle layer of the eye, a very vascular and pigmented tissue, with its role in several ophthalmological pathologies already having been clearly established. But it was not until the last few years that we have been able to reliably and precisely measure and quantify its shape and thickness. Ultrasound technology and indocyanine green angiography were the first techniques used for the study of the choroid, and they still maintain their use and clinical indications for the diagnosis and management of several pathologies. But it was the advent of optical coherence tomography that was the greatest breakthrough in choroidal imaging. In this chapter, the past, current and future image modalities for the study of the choroid will be discussed, with special focus on optical coherence tomography and its latest developments.

Cost of myopic patients with and without myopic choroidal neovascularisation. / Costes en pacientes miopes magnos con y sin neovascularización coroidea miópica.

OBJECTIVE: To study the costs associated with high myopia (HM) with choroidal neovascularisation (mCNV) or without mCNV. METHODS: Observational, retrospective, cross-sectional, and multicentre study (HM and mCNV) conducted on adult patients. Annualised medical direct cost (MDC) from the perspective of the National Health System, the non-medical direct cost (nMDC) from the patient perspective, and productivity losses were calculated. RESULTS: A total of 137 mCNV and 48 HM patients were included (mean age [SD]: 55.1 [2.8] vs. 54.7 [13.8]; P=.2), with 80% women in both groups. The observation time (months) ranged from 17.9 (9.6) right eye (RE) and 20.0 (9.7), left eye (LE) in mCNV and 47.1 (21.5) RE/45.5 (20.7) LE in MM. A higher percentage of emergency room visits was observed in mCNV vs. HM patients (41.7 vs. 25%; P=.06) and retinal specialists (91.2 vs. 77.1%; P=.01). The MDC was higher in mCNV: € 1,985 (95% CI: 1772-2198) vs. € 356 (251-480) HM, P<.001. The nMDC was also higher in mCNV: € 256 (11-524) vs. €19 (11-26) HM, P>.4. The number of affected eyes, the follow-up time, and the mCNV were factors associated with direct costs. The impact on work productivity was higher in mCNV (quite/very concerned): 27.7 vs. 10.4% HM. The mCNV showed a significant association with activity impairment (OR: 3.47, 95% CI: 10.101-1.195). CONCLUSIONS: mCNV involves higher medical costs than HM. In addition, mCNV patients have a greater need of care and assistive devices, and greater impact of the disease in their work productivity.

Long-term outcomes of phakic patients with diabetic macular oedema treated with intravitreal fluocinolone acetonide (FAc) implants.

PURPOSE: Diabetic macular oedema (DMO) is a leading cause of blindness in working-age adults. Slow-release, nonbioerodible fluocinolone acetonide (FAc) implants have shown efficacy in the treatment of DMO; however, the National Institute for Health and Care Excellence recommends that FAc should be used in patients with chronic DMO considered insufficiently responsive to other available therapies only if the eye to be treated is pseudophakic. The goal of this analysis was to examine treatment outcomes in phakic patients who received 0.2 µg/day FAc implant. METHODS: This analysis of the phase 3 FAME (Fluocinolone Acetonide in Diabetic Macular Edema) data examines the safety and efficacy of FAc implants in patients who underwent cataract extraction before (cataract before implant (CBI) group) or after (cataract after implant (CAI) group) receiving the implant. The data were further examined by DMO duration. RESULTS: Best corrected visual acuity (BCVA) after 36 months was comparable in the CAI and CBI groups. Both the percentage of patients gaining ≥ 3 lines of vision and mean change in BCVA letter score were numerically greater in the CAI group. In addition, most patients who underwent cataract surgery experienced a net gain in BCVA from presurgery baseline as well as from original study baseline. CONCLUSIONS: These data support the use of 0.2 µg/day FAc implants in phakic as well as in pseudophakic patients. These findings will serve as a pilot for design of future studies to evaluate the potential protective effect of FAc implants before cataract surgery in patients with DMO and cataract.

[New perspectives in the approach to diabetic macular edema. Aflibercept therapy]. / Nuevas perspectivas en el abordaje del edema macular diabético. Tratamiento con aflibercept.

The VISTA and VIVID trials were conducted to compare the safety and efficacy of two intravitreal injection (IVI) regimens of aflibercept versus macular laser photocoagulation for the treatment of diabetic macular edema (DME). These double-masked, phase III clinical trials randomized (461/402) patients with DME to receive either 2mg aflibercept IVI every 4 weeks (2q4) or 2mg aflibercept IVI every 8 weeks (2q8) after 5 initial monthly doses vs macular laser photocoagularion. The primary efficacy endpoint was the mean change in best corrected visual acuity (BCVA) from baseline to week 52. Secondary efficacy endpoints were the change in central retinal thickness (CRT), the proportion of patients who gained ≥10 amd ≥15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, and the change in the National Eye Institute Visual Function Questionnaire (NEI VFQ-25) in near and distance vision. The mean BCVA gains in the 2q4 and 2q8 groups versus the laser group were 12.5 and 10.7 versus 0.2 letters (p<0.0001) in VISTA, and 10.5 and 10.7 versus 1.2 letters (p<0.0001) in VIVID. The proportions of patients gaining ≥ 15 letters and the proportion of patients with an improvement of > 2 levels in the severity of diabetic retinopathy was significant in the treatment groups versus the laser group. Mean reductions in CRT in the 2q4 and 2q8 groups vs the laser group were 185.9 and 183.1 versus 73.3 µm (p<0.0001) in VISTA, and 195.0 and 192.4 versus 66.2 µm (p<0.0001) in VIVID. The incidences of ocular and nonocular adverse events were similar in all groups. In conclusion, IIV aflibercept demonstrated statistically significant superiority in improvement in BCVA and reduction in DME over laser, with similar efficacy in the 2q4 and 2q8 groups in VISTA and VIVID.

Rhegmatogenous retinal detachment treatment guidelines.

This paper outlines general guidelines following the initial diagnosis of rhegmatogenous retinal detachment. These include preoperative evaluation, treatment, possible intra- and post-operative complications, retinal re-detachment, and all therapeutic options available for each case. Treatment of the traumatic retinal detachment is also described, due to its importance and peculiarities. Treatment or prophylactic guidelines are suggested for the different types of retinal detachment described. These are based on both the experience of the ophthalmologists that have participated in preparing the guidelines, and also on evidence-based grading linked to bibliographical sources. However, these guidelines should not be interpreted as being mandatory. Given that there is a wide spectrum of options for treatment of retinal detachment, the surgeons' experience with one or other surgical technique will be of utmost importance in obtaining the best surgical result. As guidelines, they are intended as an additional aid to the surgeon during the decision-making process, with the expectation that the final choice will still be left to the surgeon's judgment and past experience.

BRAVO y CRUISE: ranibizumab en el tratamiento del edema macular secundario a oclusión de la vena de la retina / BRAVO and CRUISE: Ranibizumab for the treatment of macular edema secondary to retinal vein occlusion

Se describen los hallazgos de los estudios BRAVO y CRUISE, estudios multicéntricos y aleatorizados en pacientes con oclusión de rama venosa/vena central de la retina, en los que se compararon 3 grupos: 0,3 mg de ranibizumab, 0,5 mg de ranibizumab y placebo. Los pacientes recibieron tratamiento mensual durante 6 meses y a demanda siguiendo criterios anatómicos y funcionales, durante los siguientes 6 meses con 0,5 mg de ranibizumab. Los pacientes incluidos en el grupo control pudieron recibir tratamiento en esta segunda parte del estudio. Los resultados mostraron una mejoría significativa de agudeza visual y una mejoría anatómica en los grupos de tratamiento a partir del día 7 de la inyección de ranibizumab. El tratamiento a demanda con seguimiento mensual fue capaz de mantener las mejorías de agudeza visual conseguidas durante los primeros 6 meses de tratamiento. Los pacientes del grupo control que recibieron tratamiento a demanda a partir de los 6 meses mostraron una mejoría anatómica similar a la de los grupos de tratamiento y una menor mejoría visual(AU)

This article summarizes the results of the BRAVO and CRUISE trials, two randomized multicenter studies in patients with macular edema secondary to branch and central retinal vein occlusion, respectively. Randomization was 1:1:1 to 0.3 mg of ranibizumab, 0.5 mg of ranibizumab or placebo. Monthly injections were administered for 6 months followed by a 6-monthobservation period in which treatment on an on-demand (PRN) basis was applied with0.5 mg ranibizumab. Patients in the control group were also eligible for 0.5 mg ranibizumab treatment in the observation period. The results showed a significant anatomical and visual improvement in both treatment groups 7 days after the intravitreal injection. PRN treatment with monthly follow-up maintained the visual improvements achieved after the first 6 months of treatment. Patients in the control group who received PRN treatment after the first 6months showed an anatomical improvement similar to that in the treatment groups but less visual improvement(AU)

[BRAVO and CRUISE: ranibizumab for the treatment of macular edema secondary to retinal vein occlusion]. / BRAVO y CRUISE: ranibizumab en el tratamiento del edema macular secundario a oclusión de la vena de la retina.

This article summarizes the results of the BRAVO and CRUISE trials, two randomized multicenter studies in patients with macular edema secondary to branch and central retinal vein occlusion, respectively. Randomization was 1:1:1 to 0.3 mg of ranibizumab, 0.5 mg of ranibizumab or placebo. Monthly injections were administered for 6 months followed by a 6-month observation period in which treatment on an on-demand (PRN) basis was applied with 0.5 mg ranibizumab. Patients in the control group were also eligible for 0.5 mg ranibizumab treatment in the observation period. The results showed a significant anatomical and visual improvement in both treatment groups 7 days after the intravitreal injection. PRN treatment with monthly follow-up maintained the visual improvements achieved after the first 6 months of treatment. Patients in the control group who received PRN treatment after the first 6 months showed an anatomical improvement similar to that in the treatment groups but less visual improvement.

[Guidelines of clinical practice of the SERV: treatment of exudative age-related macular degeneration (AMD)]. / Guías de práctica clínica de la SERV: tratamiento de la degeneración macular asociada a la edad (DMAE) exudativa.

OBJECTIVE: Age related macular degeneration (ARMD) in its neovascular form is a serious disease which produces legal blindness in many patients with poor prognosis if left untreated. We intend to establish a clinical guide with the different therapeutic options that exist nowadays, which may help the ophthalmologists in their clinical practice. METHODS: A group of medical retina experts selected by SERV have evaluated the results of different published studies with the drugs currently available, obtaining an evidence-based consensus. Some recommendations have been established for diagnosis, treatment and monitoring of patients with neovascular ARMD. RESULTS: The intravitreal injection of ranibizumab at a dosage of 0.5 mg produces significant improvement of visual acuity in subfoveal lesions, according to data obtained from studies with the highest level of evidence. It should be considered as a first choice drug. The use of bevacizumab, a drug with not approved indication for intraocular use, nor for the treatment of neovascular ARMD can reach a result which is closer to the ones obtained with ranibizumab than to those obtained with photodynamic therapy (PDT) and pegaptanib. The use of intravitreal pegaptanib sodium in intravitreal injection at a dosage of 0.3 mg as a treatment for subfoveal lesions can obtain similar results to the TFD, but with a wider range of injuries. CONCLUSION: The results of the evidence-based studies are a good guide for the treatment of this disease.