The role of retinal fluid location in atrophy and fibrosis evolution of patients with neovascular age-related macular degeneration long-term treated in real world.

PURPOSE: To assess the effect of clinical factors on the development and progression of atrophy and fibrosis in patients with neovascular age-related macular degeneration (nAMD) receiving long-term treatment in the real world. METHODS: An ambispective 36-month multicentre study, involving 359 nAMD patients from 17 Spanish hospitals treated according to the Spanish Vitreoretinal Society guidelines, was designed. The influence of demographic and clinical factors, including the presence and location of retinal fluid, on best-corrected visual acuity (BCVA) and progression to atrophy and/or fibrosis were analysed. RESULTS: After 36 months of follow-up and an average of 13.8 anti-VEGF intravitreal injections, the average BCVA gain was +1.5 letters, and atrophy and/or fibrosis were present in 54.8% of nAMD patients (OR = 8.54, 95% CI = 5.85-12.47, compared to baseline). Atrophy was associated with basal intraretinal fluid (IRF) (OR = 1.87, 95% CI = 1.09-3.20), whereas basal subretinal fluid (SRF) was associated with a lower rate of atrophy (OR = 0.40, 95% CI = 0.23-0.71) and its progression (OR = 0.44, 95% CI = 0.26-0.75), leading to a slow progression rate (OR = 0.34, 95% CI = 0.14-0.83). Fibrosis development and progression were related to IRF at any visit (p < 0.001). In contrast, 36-month SRF was related to a lower rate of fibrosis (OR = 0.49, 95% CI = 0.29-0.81) and its progression (OR = 0.50, 95% CI = 0.31-0.81). CONCLUSION: Atrophy and/or fibrosis were present in 1 of 2 nAMD patients treated for 3 years. Both, especially fibrosis, lead to vision loss. Subretinal fluid (SRF) was associated with good visual outcomes and lower rates of atrophy and fibrosis, whereas IRF yields worse visual results and a higher risk of atrophy and especially fibrosis in routine clinical practice.

Clinical-Decision Criteria to Identify Recurrent Diabetic Macular Edema Patients Suitable for Fluocinolone Acetonide Implant Therapy (ILUVIEN®) and Follow-Up Considerations/Recommendations.

Current management of diabetic macular edema (DME) predominantly involves treatment with short-acting intravitreal injections of anti-vascular endothelial growth factors (anti-VEGFs) and/or corticosteroids; however, short-acting therapies (lasting between 1 and 6 months) require frequent injections to maintain efficacy, meaning a considerable treatment burden for diabetic patients with multiple comorbidities. Continuous injections needed in some cases are an economic burden for patients/healthcare system, so real-life clinical practice tends to adopt a reactive approach, ie, watch and wait for worsening symptoms, which consequently increases the risk of undertreatment and edema recurrence. On March 7th 2019, a group of experts in retinal medicine and surgery held a roundtable meeting in Madrid, Spain to discuss how to (1) optimize clinical outcomes through earlier use of fluocinolone acetonide (FAc) implant (ILUVIEN®) in patients with persistent or recurrent DME despite therapy; and, (2) to provide guidance to assist physicians in deciding which patients should be treated with ILUVIEN. In this regard, a 36-month follow-up consensus protocol is presented. In conclusion, patients that achieve a complete or partial anatomical, and preferably functional, response following one or two intravitreal dexamethasone implants, but with recurrence of edema after 3-4 months, are deemed by the authors most likely to benefit from ILUVIEN, and the switch to FAc implant should not be delayed more than 12 months after the initiation of at least the first dexamethasone implant.

Budget impact analysis of dexamethasone intravitreal implant for the treatment of diabetic macular oedema.

OBJECTIVE: To assess the economic impact following the inclusion of an intravitreal implant of dexamethasone for the treatment of diabetic macular oedema in a healthcare area in Spain. METHOD: A 3-year budget impact model was designed to estimate healthcare  direct costs for adult patients with diabetic macular oedema from the National  Health System perspective. The approved therapies in use  (aflibercept/ranibizumab/dexamethasone) were considered. The target  population was estimated from published diabetic macular oedema prevalence  (6.41%) and incidence (0.82%) for a population of 25,000 adults.  Dexamethasone was assumed to be used annually in 20%, 30% and 40% of  patients, respectively. Annual total costs included: drug acquisition (based on  frequency of injections per every year, considering exfactory prices with  mandatory deduction and split of vials), intravitreal administration, patient  monitoring, management of cardiovascular and ocular adverse events  (cataracts, increased intraocular pressure, endophthalmitis, vitreous  haemorrhage and retinal detachment). Detailed resource consumption reflecting  clinical practice was provided from local experts in retina and vitreous. Unitary  costs (€, 2016) were obtained from national databases and literature. Sensitivity  analyses were performed to assess model robustness. RESULTS: The inclusion of intravitreal dexamethasone implant would lead to  annual cost savings of €35,030 (-4.2%), €10,743 (-1.8%) and €5,051 (-0.9%), years 1-3 respectively. Total costs were reduced mainly by the fewer annual  injections required by dexamethasone. The average annual incremental costs  were -€350, -€96 and -€41 per patient. CONCLUSIONS: The inclusion of an intravitreal dexamethasone implant for the  treatment of diabetic macular oedema would lead to cost-savings for the  considered health area, mainly by reducing the administration costs.

Objetivo: Determinar el impacto económico tras la inclusión del implante intravítreo de dexametasona para el tratamiento del edema macular diabético en un área sanitaria en España.Método: Se diseñó un modelo de impacto presupuestario a tres años para  estimar los costes directos en pacientes adultos con edema macular diabético,  desde la perspectiva del Sistema Nacional de Salud, considerando terapias  intravítreas actualmente utilizadas (aflibercept/ranibizumab/dexametasona). La  población diana se obtuvo a partir de la prevalencia (6,41%) e incidencia  (0,82%) del edema macular diabético publicadas para una población de 25.000  pacientes adultos. Se asumió un 20%, 30% y 40% anual de pacientes tratados  con dexametasona, respectivamente. El coste total incluyó: coste farmacológico  (precio de venta del laboratorio con deducción obligatoria y fraccionamiento de  viales, según frecuencia de inyecciones necesarias cada año de tratamiento),  administración intravítrea, seguimiento de pacientes y manejo de eventos  oculares (cataratas, hipertensión ocular, endoftalmitis, hemorragia intravítrea y  desprendimiento de retina) y cardiovasculares. El consumo de recursos según la  práctica habitual fue estimado por expertos en retina y vítreo. Los costes  unitarios (€, 2016) se obtuvieron de la literatura y de bases de datos nacionales.  Los análisis de sensibilidad evaluaron la robustez del modelo. Resultados: La inclusión del implante intravítreo de dexametasona supondría reducciones de 35.030 € (­4,2%), 10.743 € (­1,8%) y 5.051 € (­ 0,9%) cada año, respectivamente, disminuyendo principalmente por el menor  número anual de inyecciones requeridas con dexametasona. La reducción anual  promedio supondría 350 €, 96 € y 41 € por paciente.Conclusiones: La inclusión del implante intravítreo de dexametasona para el  tratamiento del edema macular diabético supone ahorros para el área sanitaria  considerada, fundamentalmente por la reducción de costes de administración.

Clinical Decision-Making when Treating Diabetic Macular Edema Patients with Dexamethasone Intravitreal Implants.

Diabetes mellitus (DM) is a metabolic disease frequently associated with comorbidities that include diabetic macular edema (DME). The current medical approach to treating DME involves intravitreal injections with either anti-vascular endothelial growth factors or steroids. However, the burden associated with intravitreal injections and DM-derived complications is high, underlining the need to find optimal treatment regimens. In this article we describe the considerations we apply when treating DME patients with dexamethasone intravitreal implants (Ozurdex®), particularly those that influence the clinical decision-making process during the follow-up period. These considerations are based both on the available medical literature and on our clinical experience following the use of these implants in this type of patient, the goal being to optimize the number of injections and the clinical outcome of this therapy. We also provide a general overview of the pathophysiology of DME, highlighting the inflammatory component as a rationale to use steroids in these patients.

Microcephaly-lymphedema-chorioretinal dysplasia associated with pachymicrogyria and atrophy of the cerebellar vermis: an integration of brain-ocular migration disorders.

BACKGROUND: Microcephaly-lymphedema-chorioretinal dysplasia (OMIM 152950) is a rare malformative inherited disorder that can be associated with other systemic features. Other ocular and brain anomalies rather than microcephaly and chorioretinal dysplasia have been inconstantly reported in this syndrome. METHODS: We present a case of microcephaly-lymphedema-chorioretinal dysplasia with a dysmorphic facies, hypertonicity in the extremities and neuropsychomotor delay. Ophthalmological examination revealed bilateral nystagmus, microphthalmia, posterior subcapsular cataratacts, extensive chorioretinal dysplasia, optic nerve aplasia, persistent fetal vasculature, and absent retinal vessels. RESULTS: Magnetic resonance revealed pachymicrogyria and discrete atrophy of vermis cerebelosum and confirmed optic nerve hypoplasia. CONCLUSIONS: The developmental alterations observed in the retina of this patient could be analogous to central nervous system anomalies, reflecting a reduction in neural population. Ophthalmic examination of children with microcephaly is warranted.

Prospective clinical trial evaluating the efficacy of photodynamic therapy for symptomatic circumscribed choroidal hemangioma.

PURPOSE: To evaluate photodynamic therapy (PDT) for symptomatic circumscribed choroidal hemangioma (CCH). DESIGN: Prospective, multicenter, nonrandomized clinical trial. PARTICIPANTS: Thirty-one eyes of 31 patients with posterior pole CCH and symptoms caused by exudation into the macular area. INTERVENTION: Photodynamic therapy was applied by Zeiss laser. Intravenous verteporfin at 6 mg/m(2) body surface was administered before treatment, and light emitted at 689 nm for photosensitization. The treatment spot diameter was calculated on early-phase frames of pretreatment indocyanine green angiography. Fifteen minutes after starting the verteporfin infusion, the laser beam was applied to the retina at radiant exposure 50 J/cm(2) and exposure time 83 seconds. One to 4 treatments were applied at 12-week intervals over 1 year. Standardized evaluation was performed before and at 4-week intervals after each treatment, and at 3, 6, 9, and 12 months. All patients were followed for >or=12 months. MAIN OUTCOME MEASURES: The primary outcome measure was the absence of exudative retinal detachment at the 12-month follow-up visit on ophthalmoscopy, fluorescein angiography, and optical coherence tomography. Secondary measures were the visual acuity outcome, with best-corrected visual acuity determined by the Early Treatment for Diabetic Retinopathy Study chart, tumor thickness decrease on B-scan ultrasonography, and adverse events. RESULTS: Among the total, 82.8% of patients required 1, 13.8% 2, and 3.4% 3 PDTs to eliminate exudative retinal detachment. Visual acuity increased from a mean of 20/60 to 20/35 (P<0.001). Sixty-nine percent of patients demonstrated visual recovery (P<0.001). Cystoid macular edema regressed in all cases and exudative macular detachment disappeared in all but 2 cases. The CCH thickness decreased in all cases from a mean of 3.0 to 1.7 mm, with the most intense effect seen after 4 weeks of treatment (P<0.001). Visual fields showed resolution of central scotomas. There were no severe adverse events. CONCLUSIONS: Combining PDT with the standard age-related macular degeneration protocol is an effective treatment for CCH in terms of resolution of exudative subretinal fluid and recovery of VA. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.