Blood Phytosterol Concentration and Genetic Variant Associations in a Sample Population.

The main objective of this study was to determine plasma levels of PS and to study SNVs rs41360247, rs4245791, rs4148217, and rs11887534 of ABCG8 and the r657152 SNV at the ABO blood group locus in a sample of a population treated at our hospital, and to determine whether these SNVs are related to plasma PS concentrations. The secondary objective was to establish the variables associated with plasma PS concentrations in adults. Participants completed a dietary habit questionnaire and a blood sample was collected to obtain the following variables: campesterol, sitosterol, sitostanol, lanosterol, stigmasterol, biochemical parameters, and the SNVs. In addition, biometric and demographic variables were also recorded. In the generalized linear model, cholesterol and age were positively associated with total PS levels, while BMI was negatively related. For rs4245791, homozygous T allele individuals showed a significantly lower campesterol concentration compared with C homozygotes, and the GG alleles of rs657152 had the lowest levels of campesterol compared with the other alleles of the SNV. Conclusions: The screening of certain SNVs could help prevent the increase in plasma PS and maybe PNALD in some patients. However, further studies on the determinants of plasma phytosterol concentrations are needed.

Intravitreal Aflibercept for Neovascular Age-Related Macular Degeneration Beyond One Year of Treatment: AZURE, a Randomized Trial of Treat-and-Extend vs. Fixed Dosing.

INTRODUCTION: AZURE was a 76-week, randomized, open-label, parallel-group, phase IIIb noninferiority study comparing the efficacy and safety of intravitreal aflibercept (IVT-AFL) in a treat-and-extend (T&E) regimen with fixed dosing in patients with neovascular age-related macular degeneration (nAMD) previously receiving IVT-AFL for ≥ 1 year. METHODS: Patients were aged ≥ 51 years and had completed ≥ 1 year of IVT-AFL treatment prior to enrollment (IVT-AFL once per month [- 1 or + 2 weeks] for 3 months followed by IVT-AFL every 2 months [6-12 weeks]). Patients were randomly assigned (1:1) to receive IVT-AFL 2 mg in either a T&E (minimum treatment interval of 8 weeks with no upper limit, adjusted according to functional and anatomic outcomes, as assessed by the investigator; n = 168), or a fixed dosing regimen (treatment every 8 weeks [± 3 days]; n = 168). The primary endpoint was best-corrected visual acuity (BCVA) change from baseline to week (W) 52. The key secondary endpoint was the proportion of patients maintaining vision (< 15-letter loss) at W52. RESULTS: The full analysis set comprised 332 patients (T&E: n = 165; fixed dosing: n = 167). Mean BCVA change (baseline to W52) was - 0.3 ± 7.5 vs. - 0.5 ± 8.4 letters (T&E vs. fixed dosing; least-squares mean difference [95% CI]: 0.22 [- 1.51 to 1.96] letters; P < 0.0001 for noninferiority test [5-letter margin]). From baseline to W52, 95.2% (T&E) and 94.0% (fixed dosing) of patients maintained vision. Mean central subfield thickness change from baseline to W52 was - 24 ± 55 (T&E) and - 33 ± 47 (fixed dosing) µm. Last treatment interval to W76 was ≥ 12 weeks for 37.0% of T&E patients. No new safety signals were identified. CONCLUSION: IVT-AFL T&E can achieve similar functional and anatomic outcomes to fixed dosing every 8 weeks over 52 weeks in patients with nAMD who have completed ≥ 1 year of treatment, while reducing treatment burden. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02540954.

Role of intraretinal and subretinal fluid on clinical and anatomical outcomes in patients with neovascular age-related macular degeneration treated with bimonthly, treat-and-extend and as-needed ranibizumab in the In-Eye study.

PURPOSE: To assess the effect of fluid status at baseline (BL) and at the end of the loading phase (LP) of three different ranibizumab regimens: treat-and-extend (T&E), fixed bimonthly (FBM) injections and pro re nata (PRN), in patients with neovascular age-related macular degeneration (nAMD). DESIGN: Post hoc analysis of the In-Eye study (phase IV clinical trial). METHODS: Patients were randomized 1:1:1 to the three study arms and were treated accordingly. The presence and type of fluid, intraretinal fluid (IRF) or subretinal fluid (SRF) and the anatomical and visual outcomes were analysed. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA), the mean change from baseline BCVA (BL BCVA), and the proportion of eyes gaining more than 15 letters or losing more than five letters were analysed. Morphological characteristics including the subtype of choroidal neovascular membrane and the development of atrophy and fibrosis were also evaluated. RESULTS: Patients with SRF at LP had better visual outcomes than patients with IRF. The persistence of SRF did not affect the mean change from BL BCVA among the three treatment regimens. However, in patients with IRF mean change from BL BCVA was significantly lower in the FBM group. The presence of IRF at BL and at the end of the loading phase was associated with the development of fibrosis at the end of the study; this result was contrary to that observed for patients with SRF. CONCLUSIONS: While SRF is compatible with good visual and anatomical outcomes, IRF leads to worse results in patients with nAMD; our results suggest that patients with IRF have better outcomes when individualized treatment regimens are used (PRN or T&E) in contrast with a FBM regimen.

Bimonthly, treat-and-extend and as-needed ranibizumab in naïve neovascular age-related macular degeneration patients: 12-month outcomes of a randomized study.

PURPOSE: To assess the noninferiority of the treat-and-extend (T&E) and fixed bimonthly regimens of 0.5 mg intravitreal ranibizumab as compared with the pro re nata (PRN) in naïve patients with neovascular age-related macular degeneration (nAMD). METHODS: Phase IV, randomized, 12-month, multicentre trial. Patients aged ≥50 years with nAMD and visual impairment [best-corrected visual acuity (BCVA) between 23 and 78 Early Treatment Diabetic Retinopathy Study (ETDRS) letters] were eligible. Patients (one eye per patient) were randomized to bimonthly, n = 103, T&E, n = 99 or PRN, n = 104. Noninferiority was established at five letters ETDRS. RESULTS: The mean (95% CI) difference in BCVA at 12 months was 7.2 (4.2-10.2), 6.4 (2.9-9.8), and 8.0 (51.1-11.0) in the bimonthly, T&E and PRN, respectively. The bimonthly or T&E regimens were not inferior to the PRN scheme. All regimens were associated with a significant reduction of central subfield thickness and volume. The mean (95% CI) number of injections in the bimonthly regimen (7.6, 7.5-7.7) was similar as compared with the PRN regimen (7.4, 6.7-8.0) (p = 0.159) but lower than in the T&E regimen (9.3, 8.9-9.7) (p < 0.001). CONCLUSION: At 12 months, bimonthly and T&E ranibizumab were noninferior to PRN in naïve nAMD.

Early and intermediate age-related macular degeneration: update and clinical review.

Age-related macular degeneration (AMD) is the leading cause of irreversible central vision loss in developed countries. With the aging of population, AMD will become globally an increasingly important and prevalent disease worldwide. It is a complex disease whose etiology is associated with both genetic and environmental risk factors. An extensive decline in the quality of life and progressive need of daily living assistance resulting from AMD among those most severely affected highlights the essential role of preventive strategies, particularly advising patients to quit smoking. In addition, maintaining a healthy diet, controlling other risk factors (such as hypertension, obesity, and atherosclerosis), and the use of nutritional supplements (antioxidants) are recommendable. Genetic testing may be especially important in patients with a family history of AMD. Recently, unifying criteria for the clinical classification of AMD, defining no apparent aging changes; normal aging changes; and early, intermediate, and late AMD stages, are of value in predicting AMD risk of progression and in establishing recommendations for the diagnosis, therapeutic approach, and follow-up of patients. The present review is focused on early and intermediate AMD and presents a description of the clinical characteristics and ophthalmological findings for these stages, together with algorithms for the diagnosis and management of patients, which are easily applicable in daily clinical practice.

A review of current management of vitreomacular traction and macular hole.

The paper presents a review of the sequence of events of posterior vitreous detachment (PVD), vitreomacular adhesion (VMA), vitreomacular traction (VMT), and macular hole (MH) from their pathophysiological aspects, clinical features, diagnostic implications, and current management strategies. A treatment algorithm to be used in clinical practice in patients with VMA, VMT, and MH based on the presence of symptoms, visual acuity, associated epiretinal membrane, and width of the vitreous attachment is presented. Observation, pharmacologic vitreolysis with ocriplasmin, and surgical treatment are positioned as treatment options in the different steps of the therapeutic algorithm, with clear indications of the paths to be followed according to the initial presenting manifestations and the patient's clinical course.

Clinical Course of a Presumed Metastatic Uveal Melanoma to the Contralateral Choroid.

We present the ultrasound and optic coherence tomography follow-up of a presumed choroidal metastasis from a contralateral melanoma. A 53-year-old male was diagnosed with uveal melanoma with extraescleral extension in his left eye. A year later, the fundus examination revealed a flat, gray-green, pigmented choroidal lesion in the right eye. The ultrasonography showed a mass, almost flat, and all these findings were compatible with a choroidal melanocytic lesion with risk factors for growth. One month later, melanocytic skin lesions appeared on the scalp, as well as small tumors. Three months later, an ultrasonography on B scan showed a growth of the tumor size. The patient developed a progressive deterioration and died. Three possibilities can explain the occurrence of a choroidal pigmented tumor in the contralateral eye: first, bilateral primary choroidal melanomas; second, both choroidal tumors are metastatic in origin from an unknown primary melanoma; and third, the contralateral tumor is a metastatic tumor from the primary choroidal melanoma.

Pigmented free-floating vitreous cyst.

A 45-year-old man presented with a mobile shadow in the central visual field of his left eye for the preceding 4 months. His visual acuity was not affected. Funduscopy showed a brownish, oval-shaped structure floating in the vitreous cavity of the left eye. B-scan ultrasound demonstrated an oval-spherical hypoechogenic structure floating at the posterior pole. The absence of pertinent medical history and normal results from systemic exploration suggested a congenital etiology. The condition was observed regularly without any evidence of change. Differential diagnosis of vitreous cysts is important in order to establish an adequate therapeutic approach.