Effect of Pro Re Nata regimen with anti-VEGF on Type 3 Macular Neovascularization - Long term outcomes.

(348 words) Introduction: The purpose of this study is to investigate long-term outcomes of intravitreal injections (IVI) of anti-vascular endothelial growth factor (VEGF) in neovascular age-related macular degeneration (nAMD) with type 3 macular neovascularization (MNV). METHODS: This retrospective study included 19 eyes of 17 patients with nAMD and type 3 MNV treated with anti-VEGF IVI with a loading dose and PRN regimen. Best corrected visual acuity (BCVA), central macular thickness (CMT), presence of macular intraretinal fluid (IRF) and subretinal fluid (SRF), flow area (FA), subfoveal choroidal thickness (CT) and macular atrophy (MA) were assessed at baseline (T0) and during follow up (T1, post loading phase; T2, one year; T3, two years, T4>2 years). The correlations between MA at the last follow-up and standard deviation (SD) values of CMT and CT during follow-up were assessed. The influence of the number of injections on the change in MA over time was also analysed. MA differences at T4 were assessed for pseudodrusen presence. RESULTS: BCVA improved significantly during follow-up (p=0.013) particularly increasing from baseline to post loading phase and then did not modify significantly thereafter. CMT significantly reduced from T0 to T1 and remained stable during follow-up (p = <0.001). MNV flow area showed a trend toward increase in the post loading phase that was not statistically significant (p=0.082) and CT decreased significantly during follow-up (p<0.001). MA changed significantly during follow-up (p<0.001) with significant increase from T0 to T3 and from T0 to T4 (p < 0.010). Cochrane Armitage test for trend showed a significant reduction (p=0.001) of macular IRF and SRF during follow-up. MA at T4 showed a significant positive correlation with SD (standard deviation) values of CMT (p=0.040) and CT (p=0.020). Indeed, the number of injections did not influence the change over time of MA (p=0.709). MA at T4 was not statistically significantly different between patients with pseudodrusen at baseline (p=0.497). CONCLUSIONS: Intravitreal anti-VEGF injections with PRN regimen in MNV type 3 showed functional and anatomical benefits. Variations of retinal thickness and choroidal thickness during treatment were related to MA modification over time.

Real-world experience with fluocinolone acetonide intravitreal implant in patients with diabetic macular edema.

OBJECTIVES: to evaluate long-term effectiveness and safety of fluocinolone acetonide (FAc) implant used as second-line treatment in patients with persistent diabetic macular edema (DME). METHODS: retrospective data chart review of 241 pseudophakic eyes of 178 patients treated with FAc from July 2017 to December 2021 in 10 medical retinal units in Italy. The primary endpoint was the change of best-corrected visual acuity (BCVA) and central macular thickness (CMT) at 2 years. A Student's paired t-test was used. Additional therapies for DME and intraocular pressure (IOP)-related events were also evaluated. RESULTS: efficacy of FAc was assessed in a subset of 111 eyes with at least 24 months of follow-up. Mean BCVA increased at 2 years by 5.1 ETDRS letters (95%CI = 2.6-7.5; p < 0.001) while mean CMT decreased by 189 µm (95% CI 151-227; p < 0.001). Thirty-eight of these eyes (34.2%) needed additional intravitreal treatments, mainly anti-VEGF. Safety was evaluated on the entire cohort of 241 eyes treated with FAc. Overall, 66 eyes (27.4%) required emergent IOP-lowering medications (typically within the first-year post FAc) while 14 eyes (5.8%) underwent trabeculectomy, mostly during the second year of follow-up. CONCLUSION: FAc implant provides a substantial long-term functional and anatomical benefit when used as second-line treatment in eyes with DME. IOP rise can be adequately managed with topical agents although some eyes may require IOP-lowering surgery.

Baseline imaging characteristics and early structural changes in macula on rhegmatogenous retinal detachment.

Animal models have demonstrated that structural changes affect the macula during peripheral rhegmatogenous retinal detachment. This study aimed to assess photoreceptors, retinal and choriocapillaris perfusion in non-macula involving rhegmatogenous retinal detachment by analyzing en-face images from structural OCTA segmented at the ellipsoid zone (EZ) level, calculating (1) "normalized" reflectivity as a surrogate biomarker of photoreceptor damage (2) perfusion density (PD), vessel length density (VLD) and vessel diameter index (VDI) of superficial capillary plexus (SCP) and deep capillary plexus (DCP) (3) perfusion density of choriocapillaris (PDCC). Twenty-one eyes affected by macula-on rhegmatogenous retinal detachment (RRD) were enrolled at the University "G. d'Annunzio", Chieti-Pescara. The fellow unaffected eye was used as control. The mean age at the onset of RRD was 60.09 ± 10.22 (range 34-83). Compared with fellow eyes, we found lower EZ "normalized" reflectivity in macula-on (0.42 ± 0.15 in fellow eyes and 0.31 ± 0.09 in macula on p = 0.004). The affected eye was also characterized by impaired perfusion in SCP (17.26 ± 3.34% in macula on and 20.56 ± 3.62% in the fellow eye p = 0.004) and CC (50.21 ± 6.20% in macula on the eye and 57.43 ± 6.20% in the fellow eye p = 0.004). Macula-on rhegmatogenous retinal detachment has subclinical changes in photoreceptors, SCP, and CC. Future longitudinal studies should evaluate if early changes could impact post-operative macular function.

Analysis of Macular Pigment Optical Density in Macular Holes with Different Border Phenotypes.

INTRODUCTION: We conducted a cross-sectional study to compare macular pigment optical density (MPOD) in eyes with idiopathic macular holes with bumpy (bbMH) and smooth borders (sbMH) and to assess the relation between MPOD and optical coherence tomography findings. Thirty eyes from thirty patients affected by idiopathic macular hole were studied. METHODS: All patients underwent SD-OCT and macular pigment optical density (MPOD) analysis. Comparison between the two border phenotypes were estimated at baseline, as well as  the differences in MPOD, minimum and basal hole diameter, tractional hole index (THI), macular hole index (MHI), diameter hole index (DHI), and ELM integrity metrics between the two groups. RESULTS: The mean MPOD was 0.09 ± 0.08 in bbMHs and 0.16 ± 0.11 in sbMHs (p = 0.010). Correlation analysis between MPOD and minimum hole  diameter revealed a negative association (rho = - 0.707, p = 0.008) in bbMH and a positive association (rho = 0.702, p = 0.019) in sbMH. MPOD and basal diameter were negatively correlated in bbMH (rho = - 0.77, p = 0.001) and positively correlated in sbMH (rho = 0.675, p = 0.019). Indeed, MPOD is negatively correlated with THI and MHI in sbMH (rho = - 0.684 p = 0.019; rho = - 0.665 p = 0.019, respectively) and positively correlated in bbMH (rho = 0.593 p = 0.037; rho = 0.658 p = 0.018, respectively). CONCLUSIONS: MPOD is significantly reduced in bbMHs compared to sbMHs. The two border phenotypes also differ for tractional and tangential indexes, possibly reflecting a different pathogenesis. Further studies are needed to understand the prognostic role of MPOD.

Choroidal Vascularity Index Fluctuations in Epiretinal Membranes in Vitreoretinal Surgery: Comparison Between Idiopathic and Diabetic Ones.

Purpose: The aim of the study was to analyze choroidal vascularity index (CVI) fluctuations in patients with epiretinal membrane after vitreoretinal surgery, comparing idiopathic and secondary diabetic ones. Methods: Thirty eyes suffering from idiopathic ERMs (I-ERMS; n = 15) and diabetic ERMs (D-ERMS; n = 15) were analyzed in this observational prospective study. Anatomical (central macular thickness) and functional (best-corrected visual acuity) parameters were analyzed preoperatively and at 1 and 3 months after vitrectomy. Perfusion findings regarding CVI and luminal area were also calculated. Results: At 1 month after surgery, the luminal area and CVI significantly decreased in the I-ERMS group, whereas they were increased in the D-ERMS group. At the 3-month follow-up, the CVI tended to return to baseline values in I-ERMS and to reduce in D-ERMS, but without any statistical differences. Conclusions: The significant change in the CVI after surgery seems to imply that the choroidal layer is affected by vitreomacular disease and can become a novel potential biomarker of predictiveness in vitreoretinal surgery. Translational Relevance: The aim of the study was to focus on the early choroidal changes to better understand initial predictive elements of long-term functional postoperative outcomes.

Long-Term Follow-Up of Brolucizumab in Macular Neovascularization.

INTRODUCTION: The aim of the study was to evaluate functional and anatomical changes in type 1 and type 2 naïve macular neovascularization (MNV) patients treated with brolucizumab injections up to 1 year of treatment (week 48). METHODS: Thirty-eight eyes of 38 patients with active MNV were enrolled at the Ophthalmology Clinic of the University "G. d'Annunzio," Chieti-Pescara, Italy. All patients were scheduled for brolucizumab intravitreal injections as per label, according to the standard HAWK and HARRIER trials guidelines. Enrolled patients underwent complete ophthalmic evaluation, including optical coherence tomography (OCT) and OCT angiography. All measurements were evaluated at baseline and then monthly up to week 48. The main outcome measures were changes in best-corrected visual acuity (BCVA); central macular thickness (CMT); subfoveal choroidal thickness (SCT); pigment epithelial detachment presence and maximum height (PEDMH); intraretinal fluid (IRF) presence, subfoveal subretinal fluid (SSRF) presence and maximum height, macular atrophy area, and neovascular membrane flow area in the slab extending from the outer retina to choriocapillaris (ORCC flow). RESULTS: CMT and BCVA significantly changed in both groups over time. ORCC flow and SCT significantly reduced in both groups over time. Atrophy areas increased from 0 to 0.17 mm2 and from 0 to 0.23 mm2 in type 1 MNV and type 2 MNV patients, respectively. PEDMH reduced in type 1 MNV from 138 µm at T0 to 96 µm at T5. Changes in fluids were noted, with SSRF thickness reduction and IRF changes in both groups. CONCLUSION: Our one-year results of treatment confirm brolucizumab to be efficient and safe in both type 1 and type 2 MNV patients, proposing novel OCT parameters as possible biomarkers of treatment.

Choriocapillaris Reperfusion in Resolved Chronic Central Serous Chorioretinopathy Treated with Eplerenone: Long-Term Effects on the Fellow Eye.

INTRODUCTION: The aim of this work is to utilize swept-source optical coherence tomography angiography (SS-OCTA) to assess the long-term changes in the choroidal and choriocapillaris (CC) layers of the fellow unaffected eye of patients with unilateral resolved chronic central serous chorioretinopathy (cCSC) following treatment with continuous oral eplerenone (EPL). METHODS: The study included 35 patients with cCSC and subretinal fluid (SRF) in one eye. SS-OCTA imaging was performed on the fellow cCSC eyes at baseline, 6 months, and 12 months during eplerenone therapy. CC OCT angiography was analyzed to determine the percentage of choriocapillaris flow deficits (FD%), the number of flow deficits (FDn), and the average area of flow deficits (FDa). RESULTS: The results demonstrated significant changes in CC flow deficits from baseline to follow-up visits. Specifically, there was a significant decrease in FD% from 28.9 ± 2.2% at baseline to 26.4 ± 1.9% at 6 months (p = 0.023), and further to 24.9 ± 1.7% at 12 months (p = 0.001). Additionally, the FD area gradually contracted over the follow-up period (p < 0.05). Conversely, there was a significant increase in the number of flow deficits compared to baseline (p < 0.05). No statistically significant changes were observed in best-corrected visual acuity (BCVA) at the follow-up visits (p > 0.05). CONCLUSIONS: The findings of this study demonstrated long-term reperfusion of the choriocapillaris in unaffected fellow cCSC eyes during continuous oral eplerenone therapy. The beneficial effects of eplerenone therapy were observed after 6 months and maintained at 1 year. These results suggest that specific mineralocorticoid receptor (MR) antagonists may be effective in promoting choriocapillaris recovery in the unaffected eyes of patients with cCSC.

Validation of an Automated Artificial Intelligence Algorithm for the Quantification of Major OCT Parameters in Diabetic Macular Edema.

Artificial intelligence (AI) and deep learning (DL)-based systems have gained wide interest in macular disorders, including diabetic macular edema (DME). This paper aims to validate an AI algorithm for identifying and quantifying different major optical coherence tomography (OCT) biomarkers in DME eyes by comparing the algorithm to human expert manual examination. Intraretinal (IRF) and subretinal fluid (SRF) detection and volumes, external limiting-membrane (ELM) and ellipsoid zone (EZ) integrity, and hyperreflective retina foci (HRF) quantification were analyzed. Three-hundred three DME eyes were included. The mean central subfield thickness was 386.5 ± 130.2 µm. IRF was present in all eyes and confirmed by AI software. The agreement (kappa value) (95% confidence interval) for SRF presence and ELM and EZ interruption were 0.831 (0.738-0.924), 0.934 (0.886-0.982), and 0.936 (0.894-0.977), respectively. The accuracy of the automatic quantification of IRF, SRF, ELM, and EZ ranged between 94.7% and 95.7%, while accuracy of quality parameters ranged between 99.0% (OCT layer segmentation) and 100.0% (fovea centering). The Intraclass Correlation Coefficient between clinical and automated HRF count was excellent (0.97). This AI algorithm provides a reliable and reproducible assessment of the most relevant OCT biomarkers in DME. It may allow clinicians to routinely identify and quantify these parameters, offering an objective way of diagnosing and following DME eyes.

Choroidal and Retinal Vascular Findings in Patients with COVID-19 Complicated with Pneumonia: Widefield Imaging.

PURPOSE: The purpose of this study was to analyze choroidal and retinal vascular alterations of both the macula and midperiphery areas in patients hospitalized for COVID-19 infection complicated with pneumonia within 30 days from discharge. METHODS: A total of 46 eyes of 23 subjects with a history of symptomatic COVID-19 infection and recent hospitalization for pneumonia were enrolled in this observational study. Patients had not been previously vaccinated against COVID-19. A group of patients homogenous for age and sex was enrolled as controls. Microvascular retinal and choroidal features of the enrolled patients were studied with widefield optical coherence tomography angiography (OCT-A). Perfusion parameters in terms of the vessel density (VD) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) and the choroidal vascularity index (CVI) on enhanced depth imaging (EDI) mode OCT scans were analyzed. RESULTS: Our cohort of patients showed a trend of reduction in VD, significantly in the SCP VD of the superior and inferior midperiphery sectors, whereas the CVI did not show significant differences between the cases and controls. Moreover, a positive correlation between CVI and vessel density in the deep capillary plexus in the macular area (VD-DCP-MAC) was found. CONCLUSION: The systemic disease due to COVID-19 can also involve the retina and choroid with multiple mechanisms: ischemic and inflammatory. Our study showed changes in perfusion occurring in the eyes of patients with a recent hospitalization for COVID-19 complicated with pneumonia and without any possible ocular effect due to the vaccines. There is still the need to better comprise how long COVID-19 actually affects vascular changes in the eye.

Bilateral Branch Retinal Vein Occlusion after mRNA-SARS-CoV-2 Booster Dose Vaccination.

PURPOSE: We report a case of a patient with a bilateral branch retinal vein occlusion (BRVO) 24 h after a booster vaccination with the mRNA-1237 vaccine. OBSERVATIONS: Fluorescein angiography, performed at three weeks follow-up, showed vascular leakage and blockage, corresponding to hemorrhage areas associated with ischemic areas in the macula and along the arcades involved in the occlusion. CONCLUSIONS: The patient was scheduled for urgent injections of intravitreal ranibizumab and laser photocoagulation of the ischemic areas. To the best of our knowledge, this is the first case described of concomitant bilateral RVO after COVID-19 vaccination. The rapid onset of the side effects in a patient with multiple risk factors for thrombotic events suggests that vulnerable microvascular conditions require detailed investigations before administration of a COVID-19 vaccine.

Choroidal and Retinal Imaging Biomarkers in Different Types of Macular Neovascularization.

BACKGROUND: The aim of this study was to investigate optical coherence tomography (OCT) and OCT angiography (OCTA) parameters in patients with neovascular age-related macular degeneration (nAMD) and macular neovascularization (MNV) type 1, type 2, and type 3. METHODS: In this retrospective study, 105 treatment-naïve eyes of 105 patients (60 men and 45 women) with a definite diagnosis of active nAMD and MNV of different types and 105 frequency-matched age and gender healthy subjects were evaluated (61 men and 44 women). All subjects underwent a full ophthalmic examination and multimodal imaging assessment, including spectral domain (SD) OCT and OCTA. The main outcome measures were choroidal vascularity index (CVI), subfoveal choroidal thickness (SFCT), central macular thickness (CMT), and outer retina to choriocapillaris (ORCC) MNV flow area (ORCCFA). RESULTS: Significant differences were found in terms of CVI, CMT, and ORCCFA between MNV 1 and the two other groups. CVI was significantly different between MNV 1 and healthy control patients (p < 0.001) and between MNV 1 and MNV 2 (p < 0.001). ORCCFA and CMT were significantly different between MNV1 and MNV2 (p < 0.005). The difference in subfoveal CT between the three groups was not statistically significant (p = 0.458). A significant negative correlation was found between CVI and ORCCFA. Furthermore, CVI showed a positive correlation with subfoveal CT.

Two-surgeon, two-center evaluation of a new combined EDOF intraocular lens approach.

PURPOSE: To evaluate visual performance and quality of life after bilateral implantation of 2 extended depth-of-focus intraocular lenses (EDOF IOLs). SETTING: Ophthalmology Clinic, Department of Medicine and Science of Ageing, University "G. d'Annunzio" Chieti-Pescara, Italy, and Ophthalmic Unit, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Italy. DESIGN: Prospective clinical study. METHODS: 60 eyes of 30 patients with senile cataract were enrolled in this study. Patients underwent phacoemulsification and bilateral implantation of the Mini WELL IOL in the dominant eye and the Mini WELL PROXA IOL in the nondominant eye within a month. The main outcome measures over a 3-month follow-up period were uncorrected and corrected visual acuity at different distances (33 cm, 60 cm, and 4 m), defocus curve, contrast sensitivity, and patient satisfaction (evaluated by mean of the National Eye Institute Refractive Error Quality-of-Life instrument-42 questionnaire). RESULTS: Binocular uncorrected visual acuity at 90 days was 0.03 ± 0.11 logMAR for long distance, 0.05 ± 0.10 logMAR for intermediate distance, 0.03 ± 0.08 logMAR at 40 cm, and 0.06 ± 0.08 logMAR at 33 cm. Statistically significant differences between the 2 EDOF IOLs in favor of Mini WELL PROXA IOL were observed for uncorrected near visual acuity at 40 and 33 cm ( P < .001 and P < .001, respectively) and for distance-corrected near visual acuity at 40 cm ( P < .001). Significant differences between the 2 IOLs in the defocus curves were reported. CONCLUSIONS: In this small pilot study, bilateral implantation of Mini WELL IOL and Mini WELL PROXA IOL achieved good quantity and quality of vision.

Choroidal modifications assessed by means of choroidal vascularity index after oral eplerenone treatment in chronic central serous chorioretinopathy.

BACKGROUND: To investigate choroidal vascularity index (CVI) changes after oral eplerenone treatment in chronic central serous chorioretinopathy (cCSC) using the Spectral-domain (SD)-Optical Coherence Tomography (OCT) with enhanced depth imaging (EDI) mode. METHODS: Thirty-six eyes of 18 patients suffering from cCSC with monolateral foveal subretinal fluid (FSRF) successfully treated with oral eplerenone treatment and 18 age-matched healthy subjects were enroled in this retrospective study. EDI-OCT images obtained using Heidelberg Spectralis OCT device in patients with cCSC and FSRF (group 1); fellow eye (group 2) or healthy patients (healthy) were exported and then imported into image analysis ImageJ software for subsequent quantitative analysis. The main outcome measures were luminal area (LA) and CVI. RESULTS: A higher value of CVI was detected in group 1 compared to healthy eyes (p = 0.006). LA and CVI significantly reduced during follow up in group 1 and group 2. LA at 120 days was significantly lower compared to all previous time points both in group 1 and group 2 (p < 0.001). Median and [1st -3rd quartile] CVI values were 0.8 [0.7; 1.1] at baseline, 0.8 [0.7; 0.9] at 30 days; 0.7 [0.6; 0.9] at 60 and 90 days and 0.6 [0.5; 0.8] at 120 days in group 1 (p = 0.007) and 0.7 [0.6; 0.9] at baseline, 0.7 [0.7; 0.8] at 30 days; 0.7 [0.6; 0.7] at 60 and 90 days and 0.6 [0.6; 0.7] at 120 days in group 2 (p = 0.018). CONCLUSIONS: Choroidal vascularity index reduced in cCSC patients after oral eplerenone treatment during follow up both in eyes with SRF and fellow eyes thus demonstrating the effectiveness of mineral corticoid receptor antagonists in recovering choroidal morphology.

Long-Term Macular Vascular Changes after Primary Rhegmatogenous Retinal Detachment Surgery Resolved with Different Tamponade or Different Surgical Techniques.

Background: The aim of this study was to assess long-term macular vascular changes and their correlation with functional recovery in patients successfully treated for Macula-ON and Macula-OFF rhegmatogenous retinal detachment (RRD). Methods: This retrospective observational study included 82 eyes of 82 patients who received primary successful retinal detachment surgery, 33 Macula-ON and 49 Macula-OFF. Superficial and deep capillary plexuses (SCP and DCP) were evaluated by optical coherence tomography angiography (OCTA), and were correlated with visual acuity (VA), surgical technique and tamponade at 12 months after surgery. The fellow eyes were used as controls. Results: At 12-month follow-up, there was a significant decrease in the vessel density (VD) in the SCP in the operated eyes compared to control eyes (p < 0.05) in both the Macula-ON and Macula-OFF groups. Vessel length density (VLD) decrease in SCP was more extended in the Macula-OFF group. No difference in the DCP perfusion parameters was found, compared to controls. Subgroup analysis dependent on the type of surgery or tamponade showed no significant differences of VD and VLD. An inverse correlation was found between the SCP VD and the duration of silicone oil (SO) tamponade (p = 0.039). A significant correlation was observed between parafoveal SCP VD and final best corrected visual acuity (BCVA) (p = 0.028). The multivariate linear regression analysis showed that only the type of tamponade was significantly correlated with the final BCVA in the Macula-ON group (p = 0.004). Conclusions: Our study described long-term perfusion changes in RRD after surgery, with lower SCP VD and VLD in the operated eyes compared to the fellow ones, not influenced by type of surgery or tamponade. The choice of tamponade and SO removal timing may affect functional outcomes, especially in Macula-ON RRD. In conclusion, such functional and perfusion changes can be considered biomarkers that highlight the relevance of careful management of this sight-threatening disease.

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.

Intravitreal Dexamethasone Implant (IDI) Alone and Combined with Navigated 577 nm Subthreshold Micropulse Laser (SML) for Diabetic Macular Oedema.

BACKGROUND: The anatomical and functional changes after intravitreal dexamethasone implant (IDI) alone and combined with navigated subthreshold micropulse laser (NSML) in diabetic macular oedema (DMO) were compared. METHODS: Patients with a clinically confirmed diagnosis of non-proliferative diabetic retinopathy (NPDR) and DMO were enrolled in this prospective study and were randomly assigned to two different treatment groups: thirty patients were treated with IDI (IDI group), and the other 30 patients received IDI combined with NSML treatment (combined IDI/NSML group). All patients during a 6-month follow-up underwent best corrected visual acuity (BCVA) evaluation and spectral domain optical coherence tomography (SD OCT). The main outcome measures were: BCVA, central macular thickness (CMT); (3) choroidal vascularity index (CVI), subfoveal choroidal thickness (SCHT); and time to retreatment between IDI at baseline and the second implant in both groups. RESULTS: BCVA, CMT, and SCHT significantly decreased starting from the 1-month follow-up and CVI from 3 months in both groups. The between-group differences were significantly different from 1-month follow-up for BCVA, from 5-month follow-up for CMT and SCHT, and from 4-month follow-up for CVI. The Needed to Treat analysis indicated that six patients would have to be treated with SML after IDI in order for just one person to receive a benefit. CONCLUSIONS: the combined treatment showed good anatomical and functional outcomes for the treatment of DMO. In addition, IDI/SML seems to reduce injection frequency over time, improving patients' quality of life and reducing the socio-economic burden.

Choroidal Changes in Blood Flow in Patients with Intermediate AMD after Oral Dietary Supplement Based on Astaxanthin, Bromelain, Vitamin D3, Folic Acid, Lutein, and Antioxidants.

Background and Objectives: The aim of this study was to investigate the impact of oral administration of the combination of astaxanthin (AXT), lutein, folic acid, vitamin D3, and bromelain with antioxidants on choroidal blood flow in patients with age-related intermediate macular degeneration (AMD). Materials and Methods: Patients affected by intermediate AMD and treated with daily oral nutritional supplement with AXT, bromelain, vitamin D3, folic acid, lutein, and antioxidants for a period of at least 6 months were included in this retrospective study. A control group homogenous for age and sex was also included in the analysis. All participants underwent a complete ophthalmologic examination, spectral domain optical coherence tomography (SD-OCT), and optical coherence tomography angiography (OCTA) evaluation. Outcome measures were choroidal thickness (CHT) and choriocapillary vessel density (CCVD) after six months of AXT assumption. Results: CCVD values showed statistically significant difference between cases and controls at baseline (p < 0.001) and in the cases during follow-up (p < 0.001). The CHT measurements showed statistically significant difference between cases and controls (p = 0.002) and in the cases during follow-up (p < 0.001). Conclusions: The combined use of structural OCT and OCTA allows for a detailed analysis in vivo of perfusion parameters of the choriocapillaris and choroid and evaluation of changes of choroidal blood flow after oral nutritional supplements that affect blood flow velocity.

Early Structural and Vascular Changes after Within-24 Hours Vitrectomy for Recent Onset Rhegmatogenous Retinal Detachment Treatment: A Pilot Study Comparing Bisected Macula and Not Bisected Macula.

Background: In this study we aimed at investigating macular perfusion/anatomical changes in eyes with early onset rhegmatogenous retinal detachment (RRD) after prompt surgery within 24 hours, comparing a bisected macula and not bisected macula RRD. Methods: In this prospective observational study, 14 eyes of 14 patients who underwent within-24 hours vitreoretinal surgery for early onset RRD were enrolled. Patients were further divided into two subgroups: the not bisected macula group (NBM group) and the bisected macula group (BM group). At baseline and 3-month follow up, macular architecture and vessel analysis were assessed using optical coherence tomography angiography (OCTA) imaging. In detail, quantitative and qualitative analyses of the macular area were performed to quantify topographical retinal perfusion changes after surgery, calculating the foveal avascular zone (FAZ), vessel density (VD) and vessel length density (VLD) at the superficial capillary plexus (SCP) and deep capillary plexus (DCP). Results: Most cases (43%) were superotemporal RRD. Primary retinal reattachment was obtained in all cases, without recurrences within 3-month follow up. After surgery, a significant FAZ enlargement was observed at both the SCP and DCP level (p < 0.001; p < 0.05), with a significant effect of time noted between the two time points in the NBM and BM subanalysis (F = 3.68; p < 0.017). An excellent functional outcome was maintained for the whole follow-up. On the other hand, after surgery, perfusion parameters did not change significantly apart from the vessel density of the inferior macular sector at the DCP level (p = 0.03). Conclusions: Our findings suggest that the macular perfusion of eyes with RRD is still preserved if the surgery is performed really promptly, thus highlighting the great importance of a correct timing for surgery. OCTA analysis allows for a better understanding of the pathophysiological mechanisms underneath early vascular microarchitecture modifications of the posterior pole in retinal detachment, differentiating the two types of RRD not completely involving the fovea (BM and NBM).

Short-term comparison between navigated subthreshold microsecond pulse laser and oral eplerenone for chronic central serous chorioretinopathy.

To compare the anatomical/functional changes after navigated subthreshold pulse laser (SML) and oral eplerenone therapy for chronic central serous chorioretinopathy (cCSC). A total of 36 eyes of 36 patients suffering from cCSC treated with navigated SML (Navilas® 577s; OD-OS GmbH, near Berlin, Germany) (18 eyes, SML group) and oral eplerenone (18 eyes, eplerenone group) were enrolled in this retrospective study. Main outcome measures during a 3-month follow up period included changes of best corrected visual acuity (BCVA), central macular thickness (CMT), foveal subretinal fluid thickness (FSRFT), and subfoveal choroidal thickness (SFCT). At baseline average duration of symptoms was 6.8 ± 0.6 months in SML group and 6.4 ± 0.9 months in eplerenone group (p = 0.127). Mean BCVA, CMT and FSRFT changed significantly over time (p < 0.001). From baseline to 90 days the BCVA improved from 0.3 ± 0.1 to 0.1 ± 0.1 logMAR in SML group and from 0.3 ± 0. to 0.2 ± 0.1 logMAR in eplerenone group, CMT reduced from 357.1 ± 104.3 to 210.6 ± 46.7 µm and from 428.7 ± 107.7 to 332.5 ± 27.5 µm in SML group and eplerenone group respectively, FSRFT reduced from 144.4 ± 108.2 to 22.6 ± 37.2 µm and from 217.1 ± 105.9 to 54.4 ± 86.2 µm in SML group and eplerenone group. 55.6% of patients in SML group and 66.7% in eplerenone group showed a complete resolution of FSRFT during follow up. The interaction between group and time was statistically significant with greater absolute variation for CMT and FSRFT in SML group compared to eplerenone group (p < 0.001 and p = 0.043). SFCT did not change significantly during follow up (p = 0.083) for both groups. Both navigated SML and oral eplerenone were effective treatments showing recovery of retinal morphology and related visual acuity improvement in cCSC.

Study of nonperfusion area changes after ranibizumab intravitreal injection for diabetic macular edema by means of widefield OCT angiography.

INTRODUCTION: To evaluate changes of retinal capillary non-perfusion areas (RCNPA) and the retinal capillary vessel density (RCVD) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) using widefield optical coherence tomography angiography (WFOCTA) in patients with diabetic retinopathy (DR) and diabetic macular edema (DME) treated with intravitreal ranibizumab injection (IRI). MATERIALS AND METHODS: 24 eyes of 24 patients with DR and DME candidates to a loading dose of IRI were enrolled. All patients underwent WFOCTA with the PLEX Elite 9000 device with 15 × 9 mm scans centered on the foveal center at baseline (T0) and 1 month after each intravitreal injection at 30 days (T1), 60 days (T2), and 90 days (T3). In all patients, the variation of RCNPA and the RCVD of the of the SCP and DCP were calculated using automatic software written in Matlab (MathWorks, Natick, MA). RESULTS: The SCP showed a significant longitudinal variation of RCNPA (p = 0.04). Post-hoc analysis revealed a statistically significant reduction of RCNPA at T1 (p = 0.04) and a not significant reduction at T2 (p=0.18) and T3 (p=0.96). The DCP showed longitudinal changes of the RCNPA that tended to statistical significance (p = 0.09). Post-hoc analysis revealed a trend towards a statistically significant reduction of RCNPA at T3 (p = 0.09) not statistically significant, at T1 (p=0.17) and T2 (p=0.75). The RCVD of SCP and DCP showed no significant changes in any of the time points. CONCLUSIONS: Widefield OCT angiography showed a decrease of RCNPA after IRI, probably related to the reperfusion of retinal capillaries.