Effectiveness and safety of fluocinolone acetonide intravitreal implant in diabetic macular edema patients considered insufficiently responsive to available therapies (REACT): a prospective, non-randomized, and multicenter study.

OBJECTIVE: To assess the effectiveness and safety of the intravitreal fluocinolone-acetonide implant (FAc-i) in patients with chronic diabetic macular edema who did not sufficiently respond to other available therapies. METHODS: This was a multicenter, prospective, non-randomized, and phase-IV observational study conducted on patients with recurrent-DME who were insufficient responders to currently available therapies (REACT-Study). The primary end-point was the mean change in best-corrected-visual-acuity from baseline to month-24 values. RESULTS: Thirty-one eyes from 31 patients were included in the study. Mean age was 68.0 ± 7.7 years, and 10 (32.3%) were women. Study patients had received 5.3 ± 7.3 previous DME treatments before starting the study. In the overall study sample, BCVA improved from 56.1 ± 12.3 letters at baseline to 62.4 ± 17.0 letters at month-24 (p = 0.0510). The eyes with a baseline BCVA < 70 ETDRS letters had a significant improvement in BCVA from 53.2 ± 10.2 letters at baseline to 61.5 ± 17.9 letters at month-24 (p = 0.0165). In the overall study population, central-subfoveal-thickness (CST) was significantly reduced from 474.0 ± 135.1 µm at baseline to 333.4 ± 135.6 at month-24 (p < 0.0001). Similarly, macular-volume (MV) was significantly reduced from 10.7 ± 2.7 mm3 at baseline to 9.6 ± 2.9 mm3 (p = 0.0027) at month-24. Among the 31 study eyes, 19 (61.3%) required an additional treatment for DME. Throughout the study, 9 (29.0%) eyes required ocular hypotensive medication for controlling their intraocular-pressure and 5 (16.1%) eyes underwent cataract surgery. CONCLUSIONS: In DME eyes who did not sufficiently respond to previous therapies, the FAc-i was associated with an improvement in visual and anatomic outcomes. There were no unexpected adverse-events. TRIAL REGISTRATION NUMBER: EudraCT identifier: 2016-001680-37.

Anatomical and functional impact of verteporfin shortage in patients with chronic central serous chorioretinopathy.

BACKGROUND: To describe the functional and anatomical impact that the worldwide shortage of verteporfin has had on patients diagnosed with chronic central serous chorioretinopathy (cCSCR) whose treatment with photodynamic therapy (PDT) had to be delayed. METHODS: Prospective observational study. Patients were divided into two groups based on the time interval since PDT had been indicated: groups 1 and 2, with waiting times of less and more than 9 months respectively. Best corrected visual acuity (BCVA), the maximum height of the subretinal fluid (MSRF) and subfoveal choroidal thickness (SFCT) at the baseline visit and the last visit were compared. RESULTS: 49 eyes of 48 patients with cCSCR were included. The mean waiting time for PDT was 9.0 ±3.8 months. The mean BCVA was 69.0 ±17.1 letters and 68.9 ±16.4 letters for the baseline and last visit respectively, showing no difference (p= 0.958). Although there was no difference in the mean global BCVA, 15 eyes (30.5%) showed a deterioration of ≥5 letters, including 7 eyes (14%) with a decrease of ≥10 letters. Mean MSRF height was 151.4 ±97.2 µm and 98.2 ±83.1 µm for the baseline and last visit respectively (p= 0.005), persisting in 74.5% of the eyes. CONCLUSION: No significant impact was observed in the BCVA in cCSCR due to the shortage of verteporfin. However, one-third of patients had BCVA loss. There was a significant spontaneous decrease in MSRF, but it persisted in the majority of the patients, still susceptible to PDT.

FLUID-BASED VISUAL PROGNOSTICATION IN TYPE 3 MACULAR NEOVASCULARIZATION-FLIP-3 STUDY.

PURPOSE: To analyze the effect of fluid on visual acuity in cases of Type 3 macular neovascularization. METHODS: This multicentric, retrospective cohort study included eyes with treatment-naïve Type 3 macular neovascularization. Analysis of fluid in different compartments was performed. Group A included eyes with isolated intraretinal fluid, whereas Group B included eyes with intraretinal fluid in conjunction with subretinal fluid and/or sub retinal pigment epithelial fluid. RESULTS: Eyes in Group A (31, 55.3%) had better best-corrected visual acuity of 20/50 snellen equivalent (0.42 ± 0.31 logarithm of the minimum angle of resolution) at baseline and 20/50 snellen equivalent (0.40 ± 0.28 logarithm of the minimum angle of resolution) at complete resolution compared with Group B with visual acuity of 20/80 snellen equivalent (0.64 ± 0.35 logarithm of the minimum angle of resolution) (P = 0.0181) at baseline and 20/100 snellen equivalent (0.70 ± 0.40 logarithm of the minimum angle of resolution) (P = 0.0021) at complete resolution. Subfoveal atrophy was more in Group B (82.6% 19/23) at complete resolution in comparison to Group A (16/31, 51.6%). Eyes in Group B needed more anti-vascular endothelial growth factor injections (10.3 ± 9.0) for complete resolution compared with Group A (5.7 ± 4.8). CONCLUSION: Intraretinal fluid may be associated with good visual acuity in Type 3 macular neovascularization in contrast to other forms of neovascular age related macular degeneration. Furthermore, intraretinal fluid in isolation may need fewer injections and could probably be associated with less subfoveal atrophy.

Challenges in Diabetic Macular Edema Management: An Expert Consensus Report.

PURPOSE: This paper aimed to present daily-practice recommendations for the management of diabetic macular edema (DME) patients based on available scientific evidence and the clinical experience of the consensus panel. METHODS: A group of Spanish retina experts agreed to discuss different aspects related with the clinical management of DME patients. RESULTS: Panel was mainly focused on therapeutic objectives in DME management; definition terms; and role of biomarkers as prognostic and predictive factors to intravitreal treatment response. The panel recommends to start DME treatment as soon as possible in those eyes with a visual acuity less than 20/25 (always according to the retina unit capacity). Naïve patient was defined, in a strict manner, as a patient who, up to that moment, had never received any treatment. A refractory DME patient may be defined as the one who did not achieve a complete resolution of the disease, regardless of the treatment administered. Different optical coherence tomography biomarkers, such as disorganization of the retinal inner layers, hyperreflective dots, and cysts, have been identified as prognostic factors. CONCLUSION: This document has sought to lay down a set of recommendations and to identify key issues that may be useful for the daily management of DME patients.

CHANGES IN CHORIOCAPILLARIS, SATTLER, AND HALLER LAYER THICKNESSES IN CENTRAL SEROUS CHORIORETINOPATHY AFTER HALF-FLUENCE PHOTODYNAMIC THERAPY.

PURPOSE: To determinate the variation in thickness of the individual choroidal layers in patients with central serous chorioretinopathy treated with half-fluence photodynamic therapy. METHODS: Twenty-two eyes were evaluated with spectral-domain optical coherence tomography. The images were taken before photodynamic therapy, 3 months, and 6 months after the treatment. Two investigators performed these measurements: 1) choroidal thickness (CT), 2) Haller layer thickness, defined as the most external layer containing a 100-µm vessel, and 3) choriocapillaris + Sattler layer (C&S). Nine measurements were taken in the macular region. RESULTS: Choroidal thickness before photodynamic therapy was 471.8 µm ± 145.8. The Haller layer was 358.4 µm ± 122.6, and C&S was 114.3 µm ± 27.8. At 3-month follow-up, CT was 441.1 µm ± 150.7, Haller layer 348.8 µm ± 127.6, and C&S 92.4 µm ± 27.9. At 6-month follow-up, CT was 420.4 µm ± 118.4, Haller layer 331.8 µm ± 97.2, and C&S 89.5 µm ± 28.0. Using a multilevel mixed-effects linear regression, CT was found to be reduced at both 3 months (P < 0.03) and at 6 months (P < 0.001), Haller layer showed no significant reduction at 3 months (P = 0.483) or at 6 months (P = 0.055), and C&S showed reduction at 3 months (P < 0.001) and at 6 months (P < 0.001). Fellow nonaffected eyes showed no statistical variation at 3-month and 6-month follow-up. CONCLUSION: Reduction in CT in patients affected by central serous chorioretinopathy after half-fluence photodynamic therapy occurs primarily in the choriocapillaris and medium diameter vessel layers of the choroid in a short- and medium-term follow-up.

Structure versus function: correlation between outer retinal and choroidal thicknesses measured by swept-source OCT with multifocal electroretinography and visual acuity.

BACKGROUND: To correlate retina-choroidal anatomy as assessed via swept-source OCT (SS-OCT) with retinal function as determined by best-corrected visual acuity (BCVA) and multifocal electroretinogram (mfERG). METHODS: Thirty-three eyes from 33 patients including 16 with neovascular AMD (nvAMD) and 17 controls were included. Patients were included in the present study after a complete ophthalmologic examination, including BCVA, slit-lamp study, intraocular pressure measurement, dilated fundus examination after tropicamide instillation, SD-OCT, SS-OCT, fundus photographs and mfERG. Age, sex, BCVA, number of anti-VEGF intravitreal injections in the nvAMD group, were recollected. Outer retinal and choroidal thickness were determined at the fovea and 500 µm temporal, superior, nasal and inferior. First-order response from mfERG was collected. P1 amplitude was recorded in R1, R2 and the average of R1 + R2. The measurements recollected from the SS-OCT, mfERG and BCVA were compared. RESULTS: Better BCVA was found with thicker outer retina foveal thickness (r = 0.349; P = 0.047), with thicker subfoveal choroidal thickness (r = 0.443; P = 0.010), and with higher amplitude in P1 at R1 (r = 0.346; P = 0.037). Outer retina foveal thickness did not correlate with P1 amplitude at R1 (r = 0.072; P = 0.692), R2 (r = 0.265; P = 0.137) either with the average P1 amplitude at R1 + R2 (r = 0.253; P = 0.156). A thicker subfoveal choroidal thickness was related with higher amplitude in P1 at R1 (r = 0.383; P = 0.028), R2 (r = 0.409; P = 0.018) and the average of R1 + R2 (r = 0.419; P = 0.015). CONCLUSIONS: Choroidal thickness demonstrated a positive correlation with retinal function in the sample studied, so a thicker choroid is related to a better retinal function measured with mfERG and BCVA.

The Prevalence of Vitreomacular Interface Pathology in a Spanish Tertiary Hospital.

PURPOSE: To determine the prevalence of vitreomacular interface (VMI) pathology, using spectral-domain optical coherence tomography (SD-OCT). METHODS: VMI status was classified into macular posterior vitreous detachment (PVD), focal vitreomacular adhesion (VMA; ≤1,500 µm), broad VMA (>1,500 µm), focal vitreomacular traction (VMT; ≤1,500 µm), broad VMT (>1,500 µm), full-thickness macular hole (FTMH) with the presence of VMT, and FTMH without the presence of VMT. RESULTS: A total of 1,976 eyes were included. A nonpathologic VMI was observed in 1,875 eyes (94.8%), including 1,050 (53.1%) with PVD, 120 (6.1%) with focal VMA and 705 (35.6%) with broad VMA. A pathologic state of the VMI was diagnosed in 101 eyes (5.1%). Thirty-three eyes (1.7%) were classified as focal VMT, 29 (1.4%) as broad VMT, 39 (1.9%) as FTMH, resulting in 6 small, 12 medium and 21 large FTMHs, six eyes had VMT associated to FTMH. CONCLUSIONS: Even in a tertiary care, retinal referral practice, VMI pathology is a relatively rare condition. There was a higher prevalence in a tertiary hospital study compared to population-based studies.

En face mode of swept-source optical coherence tomography in circumscribed choroidal haemangioma.

PURPOSE: To describe the findings in circumscribed choroidal haemangioma (CCH) using en face swept-source optical coherence tomography (SS-OCT). METHODS: En face images were obtained employing DRI-1 Atlantis OCT (Topcon, Tokyo, Japan), using a three-dimensional volumetric scan of 12×9 mm. Images were obtained from the retinal pigment epithelium to 1000 µm in depth of the tumour. RESULTS: Twenty-two eyes from 22 patients with the clinical diagnosis of CCH were included. In 20 eyes (90.9%), a characteristic pattern was visualised in the en face image across the vascular tumour. A multilobular pattern, similar to a honeycomb, with hyporeflective, confluent, oval or round areas corresponding with the lumen of the tumour vascular spaces, and hyper-reflective zones, which may represent the vessels walls and connective tissue of the tumour. Ten eyes (45.4%) showed a hyper-reflective halo surrounding the tumour. Seventeen tumours (77.2%) showed small diameter vessels at the inner zone and larger vessels in the outer area. Twelve patients (54.5%) had previously received treatment (photodynamic therapy, transpupillary thermotherapy, dexamethasone intravitreal implant or brachytherapy with ruthenium-106). No differences were found between treated and untreated patients in any of the measured parameters. CONCLUSIONS: En face SS-OCT is a rapid, non-invasive, high-resolution, technology, which allows a complementary study to cross-sectional scans in CCH. A characteristic multilobular pattern, with a hyper-reflective halo surrounding the tumour, was found in en face SS-OCT images. No morphological differences were found between naïve patients and patients who received previous treatment.

Treatment of Exudative Age-related Macular Degeneration: Focus on Aflibercept.

A formulation of aflibercept for intravitreal injection (Eylea) is approved for the treatment of patients with exudative age-related macular degeneration (AMD). Aflibercept has a significantly higher affinity for Vascular endothelial growth factor (VEGF)-A compared with other monoclonal anti-VEGF antibodies. In addition to binding all VEGF-A isoforms, aflibercept also blocks other proangiogenic factors such as VEGF-B and placental growth factor. The VIEW 1 and 2 trials showed this drug achieves improved results in patients with exudative AMD similar to those obtained with monthly ranibizumab, using a bimonthly treatment regimen after a loading dose of three intravitreal injections, which translates to less use of healthcare resources. There is a subgroup of patients that present with persistent fluid after the loading dose that could benefit from monthly injections or personalized proactive treatment after the first year. In the second year of treatment, the Treat and Extend patterns can permit even more lengthening of the time between injections. More data are needed to confirm the optimal monitoring and retreatment dosing, to maintain long-term efficacy. Other preliminary data suggest that patients that do not respond to other anti-angiogenics and patients with special pathologies such as polypoidal choroidopathy or retinal angiomatous proliferation can improve upon switching to aflibercept. To date, the safety profile of aflibercept is excellent and is comparable to other anti-angiogenic treatments.

Papel del factor de crecimiento del endotelio vascular en las enfermedades de la retina / Role of VEGF in diseases of the retina

La angiogénesis es el proceso por el cual se forman nuevos vasos sanguíneos a partir de vasos preexistentes, y es el paradigma de enfermedades como el cáncer y la degeneración macular asociada a la edad exudativa1,2. Se han identificado diversos factores proangiogénicos, entre los que destaca el vascular endothelial growth factor (factor de crecimiento endotelial vascular [VEGF]), especialmente el VEGF-A, que produce la activación de las células endoteliales y promueve la proliferación celular, la migración y el aumento de la permeabilidad vascular3. El VEGF también está involucrado en la etiopatogenia de otras enfermedades retinianas como el edema macular diabético y el edema macular secundario a oclusiones venosas. Asimismo, cada vez hay más evidencia de que el placental growth factor (factor de crecimiento placentario [PIGF]) actúa sinérgicamente con el VEGF promoviendo estas enfermedades. Actualmente, los fármacos anti-VEGF aflibercept, ranibizumab y bevacizumab constituyen el principal tratamiento para estas enfermedades. Estos fármacos se diferencian en su estructura molecular y en su mecanismo de acción (AU)

Angiogenesis is the process through which new blood vessels are formed, based on preexisting vessels, and is the paradigm of diseases such as cancer and exudative ageassociated macular degeneration (ARMD).1,2 Several proangiogenic factors have been identified, such as vascular endothelial growth factor (VEGF), especially VEGF-A, which activates endothelial cells and promotes cell proliferation, migration, and an increase in vascular permeability.3 VEGF is also involved in the etiopathogenesis of other retinal diseases, such as diabetic macular edema and macular edema secondary to retinal vein occlusion. Likewise, there is increasing evidence that placental growth factor (PIGF) acts recepsynergetically with VEGF in promoting these diseases. Currently, the main treatment for these diseases are the anti-VEGF drugs, aflibercept, ranibizumab and bevacizumab. These agents differ in their molecular structure and mechanism of action (AU)

En face swept-source optical coherence tomography in neovascular age-related macular degeneration.

PURPOSE: To describe en face swept-source optical coherence tomography (SS-OCT) findings in the retinal pigment epithelium (RPE) and choroid and to correlate them with fluorescein angiography (FA) and/or indocyanine green angiography (ICGA) in neovascular age-related macular degeneration (AMD). METHODS: Thirty-eight eyes with the recent diagnosis of neovascular AMD were imaged using an SS-OCT system. En face images were obtained at RPE, choriocapillaris, Sattler's layer and Haller's layer level. Analysis of the images and correlation with colour fundus photographs, FA, ICGA in selected cases, were made. RESULTS: En face images at RPE level revealed changes in all eyes. The neovascular complex appeared hyper-reflective in 9 of 38 eyes (23.7%), and in 29 of 38 eyes (76.3%), it was hyporeflective. The choriocapillaris en face image showed pathological changes in all eyes as well, and in 20 out of 38 eyes (52.6%), the alterations were hyper-reflective, while 18 of 38 eyes (47.4%) showed hyporeflective changes. Twenty (52.6%) eyes and 19 (50.0%) had a hyper-reflective lesion in Sattler's layer and Haller's layer, respectively, and 15 (39.4%) cases showed a hyporeflective lesion in both layers. No differences were found between the neovascular complex area, horizontal and vertical diameters, measured in the en face image and FA (p=0.171, p=0.061, p=0.133, respectively). Hyporeflective changes were predominant at RPE level and hyper-reflective at choriocapillaris, Sattler's and Haller's layers. CONCLUSIONS: En face SS-OCT is a rapid, non-invasive, high-resolution, promising technology, which allows a complementary study to angiography of neovascular AMD. There is a correlation between angiography and en face SS-OCT images in neovascular AMD.

Sequential bilateral retinal artery occlusion.

An 86 year old woman experienced a sequential bilateral loss of vision over a period of less than 24 hours. Clinical findings and complementary studies suggested a bilateral atherogenic embolic event. Initially, she presented a superior branch retinal artery occlusion in her right eye followed by a central retinal artery occlusion with cilioretinal artery sparing in her left eye. Some conservative maneuvers performed did not improve visual acuity in the left eye. Supra-aortic Doppler ultrasonography revealed mild right internal carotid artery stenosis and moderate left internal carotid artery stenosis with a small, smooth, and homogeneous plaque. The transthoracic echocardiography showed a severe calcification of the mitral valve with a mild-moderate rim of stenosis. Central retinal artery occlusion and branch retinal artery occlusion are characterized by painless monocular loss of vision. Clinical approach and management attempt to treat the acute event, find the source of the vascular occlusion, and prevent further vascular events from occurring. Giant cell arteritis is a potentially treatable cause of central retinal artery occlusion and should be excluded in every single patient over 50 years old.

Correlation between spectral-domain optical coherence tomography and autofluorescence findings in sclerochoroidal calcification.

OBJECTIVE: The purpose of this article is to report the correlation between spectral domain-optical coherence tomography and autofluorescence findings in 3 consecutive cases with sclerochoroidal calcification. DESIGN: Observational case series. PARTICIPANTS: The study involved 3 patients with bilateral sclerochoroidal calcification. METHODS: B-scan ultrasonography, spectral domain-optical coherence tomography, and autofluorescence were performed in each eye. The choroidal vascular thickness and autofluorescence patterns of the calcified plaques were evaluated with spectral domain-optical coherence tomography and autofluorescence, respectively. RESULTS: An important variation of choroidal vascular thickness overlying sclerochoroidal calcification was observed in spectral domain-optical coherence tomography. Autofluorescence showed 2 patterns of autofluorescence closely correlated with changes in choroidal vascular thickness. In those zones where the thicknesses of choriocapillaris complex were reduced, a hyperautofluorescence pattern was observed in autofluorescence. The hypoautofluorescence pattern was observed in outpouching zone of retinal pigment epithelium-choriocapillaris complex seen in spectral domain-optical coherence tomography. The hypoautofluorescence pattern was closely correlated with remarkable reduction of the choriocapillaris complex. There were no significant differences between the patterns of autofluorescence except the extension. CONCLUSIONS: Spectral domain-optical coherence tomography and autofluorescence are noninvasive complementary imaging studies that may help to improve our knowledge about sclerochoroidal calcification. Characteristic patterns of autofluorescence were closely correlated with spectral domain-optical coherence tomography findings. More patients need to be evaluated with both complementary studies to establish conclusions related with these findings.