Brolucizumab intravitreal injection in macular neovascularization type 1: VA, SD-OCT and OCTA parameters changes during a 16-weeks follow up.

PURPOSE: to assess the anatomical and functional changes after brolucizumab intravitreal injection (BIVI) in macular neovascularization type 1 (MNV1). Setting/Venue: Ophthalmology Clinic, University "G. d'Annunzio" of Chieti-Pescara. METHODS: A total of 24 eyes of 24 patients suffering from naïve MNV1 candidates to BIVI as per label with q12/q8 dosing regimen after the loading dose were enrolled in this prospective study. Main outcome measures during a 16-weeks follow up period included changes of best corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal subretinal fluid thickness (SSRFT), subfoveal sub-RPE fluid thickness (SSRPEFT), subfoveal choroidal thickness (SFCT) and pigment epithelial detachment (PED) maximum height (PED-MH). In addition, percentages of eyes with intraretinal fluid, subretinal fluid and sub-RPE fluid at different time points and percentages of eyes candidates to a q8 or q 12 injection interval after disease activity assessment at week 16 were evaluated. RESULTS: BCVA improved significantly from baseline (T0) to week 12 (T3) (p=0.028). CMT showed a significant reduction from 456.0±123.0 µm at T0 to 265.0±85.0 µm at T3 (p<0.001). SSRFT and SSRPEFT reduced significantly as well (p<0.001 and p=0.049 respectively). PED-MH reduced significantly from 162.0±110.0 µm at T0 to 94.1±38.9 µm at T3 (p=0.020) and SFCT from 203.0±56.9 µm at T0 to 146.0±64.2 µm at T3 (p=0.006). IRF presence changed significantly from 41.7% of eyes at T0 to 20.8% at T3 (p=0.045). SSRF reduced significantly during follow up, being present in 62.5% of eyes at T0 and 4.2% of eyes at T3 (p<0.001). Subfoveal sub-RPE fluid decreased significantly during time being present in 20.8% of eyes at T0 and 0% at T3 (p=0.013). Most of the eyes (18 eyes, 75%) at week 16 after disease activity assessment were shifted in the q12 interval and only a minority of eyes shifted in a q8 interval (6 eyes, 25%). CC Flow and ORCC flow did not show significant differences during follow up. CONCLUSIONS: Brolucizumab is efficient in reducing all retinal fluids during the loading phase and shows reduction of macular thickness, choroidal thickness, and PED height. Most eyes at disease activity assessment (75%) fall into 12 week-interval and the minority (25%) into the 8 week-interval.

Functional and Structural Reliability of Optic Nerve Head Measurements in Healthy Eyes by Means of Optical Coherence Tomography Angiography.

Background and Objectives: the aim of the study was to evaluate the repeatability and reproducibility of optical microangiography (OMAG)-based optical coherence tomography angiography (OCTA) in the optic nerve head (ONH) and radial peripapillary capillary (RPC) perfusion assessment of healthy eyes. Materials and Methods: in this observational study, a total of 40 healthy subjects underwent ONH evaluation, using an OMAG-based OCTA system at baseline (T0), after 30 min (T1), and after 7 days (T2). The main outcome measures were the vessel density (VD) and flux index (FI) of the RPCs, as well as peri-papillary retinal nerve fibre layer (pRNFL) thickness. The analysis was performed by two observers independently. The coefficient of repeatability (CR), within the subject coefficient of variation (CVw) and intrasession correlation coefficient (ICC), to evaluate intrasession repeatability of measurements was calculated for each observer. Results: the high intrasession and intersession repeatability and reproducibility were assessed in the two observers for all three outcome measures. Of note, the CRs for the first and the second observer were 0.011 (95% confidence interval (CI) 0.009-0.014) and 0.016 (95% CI 0.013-0.020) for FI, 0.016 (95% CI 0.013-0.021) and 0.017 (95% CI 0.014-0.021) for VD, and 2.400 (95% CI 1.948-3.092) and 3.732 (95% CI 3.064-4.775) for pRNFL thickness, respectively. The agreement between them was excellent for pRNFL assessment and very good for FI and VD. Conclusion: OCTA has a great potential in the accurate assessment of ONH and peri-papillary microcirculation. It allows for repeated and reproducible measurements without multiple scans-related bias, thus guaranteeing an independent operator analysis with good reproducibility and repeatability.

Widefield Swept Source OCTA in Retinitis Pigmentosa.

(1) Background: To evaluate superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaris (CC), perfusion density (PD), and vessel length density (VLD) in macular and near/mid periphery regions in patients with retinitis pigmentosa (RP) using widefield swept source optical coherence tomography angiography (WSS-OCTA). (2) Methods: Twelve RP patients (20 eyes) and 20 age-matched subjects (20 eyes) were imaged with the SS-OCTA system (PLEX Elite 9000, Carl Zeiss Meditec Inc., Dublin, CA, USA). Quantitative analysis was performed in the macular and peripheral regions. The main outcome measures were SCP, DCP, CC, PD, and VLD in central and peripheral areas. (3) Results: Mean visual acuity, central macular thickness, and microperimetry were significantly reduced in RP patients compared to normal subjects (p < 0.05). The perfusion density and VLD of SCP, DCP, and CC were significantly reduced in RP patients compared to normal controls both in the central and peripheral retina (p < 0.05). A significant direct correlation was found in RP patients between PD of the 1.5 mm central retina both in DCP and CC and microperimetry at 4° and 8°. (4) Conclusions: Widefield SS-OCTA shows an impairment of retinal and choroidal perfusion density and vessel length density in central and peripheral retina of RP patients. The reduction of flow features correlates with the macular function.

Cone Dystrophies: An Optical Coherence Tomography Angiography Study.

BACKGROUND: This study investigates the relationship between retinal vascularization and macular function in patients with cone dystrophies (CDs). METHODS: Twenty CD patients (40 eyes) and 20 healthy controls (20 eyes) were enrolled in this prospective case-control study. Patients underwent full ophthalmological examination, microperimetry, full-field, pattern and multifocal electroretinogram (ERG, PERG, mfERG) and optical coherence tomography angiography (OCTA). Main outcome measures were as follows: foveal and parafoveal inner and outer retinal thickness; microperimetry sensitivity in the central 4° and 8°, ERG b wave amplitudes and peak times, PERG P50 and N95 amplitudes and latencies, and mfERG N1 to P1 amplitudes; and superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillary (CC) plexus vessel densities, divided into foveal and parafoveal region. RESULTS: Retinal thickness, SCP and DCP densities were significantly related to PERG. A significant relationship was found between foveal and parafoveal retinal thicknesses and foveal SCP density (p < 0.001 and p = 0.018, respectively) and between parafoveal retinal thickness and parafoveal SCP density (p = 0.002). Foveal and parafoveal retinal thicknesses were significantly related to parafoveal DCP density (p = 0.007 and p < 0.001). Foveal and parafoveal retinal thicknesses, foveal SCP and parafoveal DPC densities were significantly reduced in CD patients compared to controls (p < 0.001; p = 0.010 and p = 0.008, respectively). PERG and mfERG amplitudes were significantly reduced in CD patients compared to controls (p < 0.01). CONCLUSIONS: CD eyes showed reduced retinal thickness significantly related to reduced vessel density, possibly caused by a decreased metabolic demand. In addition, vessel density significantly correlated with loss of function.

A Custom-Made Semiautomatic Analysis of Retinal Nonperfusion Areas After Dexamethasone for Diabetic Macular Edema.

Purpose: To evaluate the changes of retinal capillary nonperfusion areas and retinal capillary vessel density of the superficial capillary plexus (SCP) and deep capillary plexus in patients with diabetes with diabetic macular edema treated with an intravitreal dexamethasone implant (IDI). Methods: We enrolled 28 patients with diabetic retinopathy and diabetic macular edema candidates to IDI. All patients underwent widefield optical coherence tomography angiography with PLEX Elite 9000 device with 15 × 9 mm scans centered on the foveal center at baseline, 1 month, 2 months, and 4 months after IDI. In all the patients, the variation of the retinal capillary nonperfusion areas and of the retinal vessel density of the SCP and deep capillary plexus were calculated using an automatic software written in Matlab (MathWorks, Natick, MA). Results: During follow-up, SCP showed a statistically significant reduction of ischemic areas at 1 month after IDI (P = 0.04) and slightly increased not significantly thereafter (P = 0.15). The percentage of nonperfusion areas changed from 11.4% at baseline, to 6.3% at 1 month, 8.1%, at 2 months, and 10.2% at 4 months. The whole vessel density of SCP slightly increased (not significantly) from 35.30% at baseline to 38.00% at 1 month, and then decreased to 37.85% at 2 months and 36.04% at 4 months (P = 0.29). Retinal capillary nonperfusion areas and retinal vessel density at the deep capillary plexus did not change significantly (P = 0.31 and P = 0.73, respectively). Conclusions: Widefield optical coherence tomography angiography showed a decrease in retinal capillary nonperfusion areas after dexamethasone implant suggesting a possible drug-related reperfusion of retinal capillaries particularly evident in the early period. Translational Relevance: A custom-made automatic analysis of retinal nonperfusion areas may allow a better and precise evaluation of ischemic changes after intravitreal therapy.

Oxidative Stress Markers and the Retinopathy of Prematurity.

Retinopathy of prematurity (ROP) is a leading cause of potentially preventable blindness in low birth weight preterm infants. Several perinatal and postnatal factors contribute to the incomplete maturation of retinal vascularization, leading to oxidative stress damage. Literature data suggest that the lack of equilibrium between pro-oxidants and anti-oxidants plays a key role. In the last decade, there has been an increasing interest in identifying the antecedents of ROP and the relevant pathogenic mechanisms involved. In this context, a panel of biomarkers was investigated in order to achieve early detection of oxidative stress occurrence and to prevent retinal damage. Several nutritional elements have been found to play a relevant role in ROP prevention. At this stage, no conclusive data have been shown to support the usefulness of one biomarker over another. Recently, the Food and Drugs Administration, the European Medicine Agency, and the National Institute of Health proposed a series of criteria in order to promote the inclusion of new biomarkers in perinatal clinical guidelines and daily practice. The aim of the present review is to offer an update on a panel of biomarkers, currently investigated as potential predictors of ROP, highlighting their strengths and weaknesses.

The role of diagnostic imaging techniques in the management of retinal detachment due to macular hole in high myopia.

After preoperative assessment revealed anomalous posterior vitreous detachment, a 75-year-old woman affected with retinal detachment due to macular hole was scheduled to undergo the posterior episcleral buckling procedure. Preoperative microperimetry showed unstable eccentric fixation with a dense scotoma within the central 8 degrees. One month postoperatively, best-corrected visual acuity increased from 1.70 to 0.88 logarithm of the minimum angle of resolution. Ultrasonography and optical coherence tomography revealed the indentation of the posterior scleral profile due to the buckle. The retina appeared fully attached and a macular hole with flattened edges was still detectable. Microperimetry showed stable central fixation with recovery of retinal sensitivity within the central 2 degrees. Diagnostic imaging techniques guided the decision to use the posterior episcleral buckling procedure. Microperimetry was useful to explain vision improvement despite residual macular hole.

The ocular surface after successful glaucoma filtration surgery: a clinical, in vivo confocal microscopy, and immune-cytology study.

We investigated the ocular surface (OS) system modifications after completely successful glaucoma surgery in thirty-eight patients undergoing trabeculectomy (surgical group), using laser scanning confocal microscopy (LSCM) and impression cytology (IC). Twenty-six medically controlled glaucomatous patients served as controls (medical group). LSCM, IC, and the ocular surface disease index (OSDI) and National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) questionnaires, were performed at baseline and after six months. The main outcomes were: goblet cell density (GCD), limbal dendritic cell density (LDCD), subbasal corneal nerve inhomogeneity (SCNI), Meibomian gland density and inhomogeneity (MGD, MGI), and HLA-DR positivity. There were no significant baseline differences between groups. At the sixth month, the surgical group showed a GCD increase (p < 0.001), and a LDCD, SCNI, MGI, HLA-DR (p < 0.001), OSDI and NEI VFQ-25 scores decrease (p < 0.05). The medical group did not show significant OS modifications, showing LSCM and IC parameters significantly worse compared to the surgical group (p < 0.001). The OSDI score correlated with GCD, MGI, SCNI, LDCD, and HLA-DR (p < 0.001; p < 0.05; p < 0.01). The present study found that the whole OS system objectively improved after completely successful glaucoma filtration surgery. These changes positively affected the OSDI score, but not the NEI VFQ-25 score.

Early retinal flow changes after vitreoretinal surgery in idiopathic epiretinal membrane using swept source optical coherence tomography angiography.

(1) Background: The aim of this observational cross-sectional work was to investigate early retinal vascular changes in patients undergoing idiopathic epiretinal membrane (iERM) surgery using swept source optical coherence tomography angiography (SS-OCTA); (2) Methods: 24 eyes of 24 patients who underwent vitrectomy with internal limiting membrane (ILM) peeling were evaluated pre- and postoperatively using SS-OCTA system (PLEX Elite 9000, Carl Zeiss Meditec Inc., Dublin, CA, USA). For each eye, five 6x6-mm OCTA volume scans were acquired by two observers independently. The en face images of superficial capillary plexus (SCP) were then exported to imageJ and a semi-automated algorithm was used for subsequent quantitative analysis. Perfusion density (PD), vessel length density (VLD), vessel diameter index (VDI) and vessel tortuosity (VT) of SCP were evaluated in both the parafoveal (2.5 mm diameter) and perifoveal areas (5.5 mm diameter); (3) Results: At OCTA analysis statistically significant differences were found between controls and diseased eyes for all parameters in parafoveal and perifoveal regions (p<0.001; p<0.05) except for perifoveal VLD. During 6-month follow up, both anatomical/perfusion and functional parameters showed a statistically significant improvement if compared to preoperative values. In detail, at one month post vitrectomy, VLD and VT significantly changed in parafoveal region (p=0.043; p=0.045), while PD and VDI showed a trend of increase in both parafoveal and perifoveal region. At 6 months after surgery, PD, VLD and VT of parafoveal region significantly improved (p=0.021, p=0.018, p=0.047 respectively). (4) Conclusions: SS-OCTA provides a quantitative and qualitative analysis of the superficial capillary plexus allowing for early vascular changes assessment after vitrectomy with iERM and ILM peeling.

Foveal avascular zone area and parafoveal vessel density measurements in different stages of diabetic retinopathy by optical coherence tomography angiography.

AIM: To investigate foveal avascular zone (FAZ) and parafoveal vessel densities (PRVD) by means of optical coherence tomography angiography (OCTA) in diabetic patients with or without diabetic retinopathy (DR) and to assess the reproducibility of FAZ and PRVD measurements. METHODS: Sixty diabetic patients (60 eyes) with different stage of DR (graded according to the International Clinical Severity Scale for DR) and 20 healthy subjects underwent FAZ area and PRVD measurements using OCTA by two experienced examiners. FAZ area in all patients was also assessed using fluorescein angiography (FA). RESULTS: In subject with proliferative DR and with moderate-severe non proliferative DR, FAZ area was significantly increased compared to healthy controls (P=0.025 and P=0.050 respectively measured with OCTA and P=0.025 and P=0.048 respectively measured with FA). OCTA showed significantly less inter-observer variability compared to FA. Concordance correlation coefficient (CCC) for FAZ area measurements was 0.829 (95%CI: 0.736-0.891) P<0.001 with FA and 1.000 (95%CI: 0.999-1.000) P<0.001 with OCTA. CCC was 0.834 (95%CI: 0.746-0.893) P<0.001 and 0.890 (95%CI: 0.828-0.930) P<0.001 for parafoveal superficial and deep vessel density measurements, respectively. CONCLUSION: OCTA shows progressive increase of FAZ area and reduction of PRVD in both superficial and deep plexus at increasing DR severity. FAZ area and PRVD measurements using OCTA are highly reproducible.