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.

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.

Subretinal Pseudocysts: A Comprehensive Analysis of this Novel OCT Finding.

INTRODUCTION: In current clinical practice, several optical coherence tomography (OCT) biomarkers have been proposed for the assessment of severity and prognosis of different retinal diseases. Subretinal pseudocysts are subretinal cystoid spaces with hyperreflective borders and only a few single cases have been reported thus far. The aim of the study was to characterize and investigate this novel OCT finding, exploring its clinical outcome. METHODS: Patients were evaluated retrospectively across different centers. The inclusion criterion was the presence of subretinal cystoid space on OCT scans, regardless of concurrent retinal diseases. Baseline examination was set as the first time the subretinal pseudocyst was identified by OCT. Medical and ophthalmological histories were collected at baseline. OCT and OCT-angiography were performed at baseline and at each follow-up examination. RESULTS: Twenty-eight eyes were included in the study and 31 subretinal pseudocysts were characterized. Out of 28 eyes, 16 were diagnosed with neovascular age-related macular degeneration (AMD), 7 with central serous chorioretinopathy, 4 with diabetic retinopathy, and 1 with angioid streaks. Subretinal and intraretinal fluid were present in 25 and 13 eyes, respectively. Mean distance of the subretinal pseudocyst from the fovea was 686 µm. The diameter of the pseudocyst was positively associated with the height of the subretinal fluid (r = 0.46; p = 0.018) and central macular thickness (r = 0.612; p = 0.001). At follow-up, subretinal pseudocysts disappeared in most of the reimaged eyes (16 out of 17). Of these, two patients presented retinal atrophy at baseline examination and eight patients (47%) developed retinal atrophy at follow-up. Conversely, seven eyes (41%) did not develop retinal atrophy. CONCLUSION: Subretinal pseudocysts are precarious OCT findings, usually disclosed in a context of subretinal fluid, and are probably transient alterations within the photoreceptor outer segments and retinal pigment epithelium (RPE) layer. Despite their nature, subretinal pseudocysts have been associated with photoreceptor loss and incomplete RPE definition.

The retinal neurovascular coupling is impaired in men with vasculogenic erectile dysfunction.

The aim of this study was to study the retinal vessels in patients affected by vasculogenic erectile dysfunction (ED), using dynamic vessel analyzer (DVA). Patients with vasculogenic ED and control subjects were prospectively enrolled to undergo a complete urological and ophthalmologic evaluation, including DVA and structural optical coherence tomography (OCT). The main outcome measures were: (1) arterial dilation; (2) arterial constriction; (3) reaction amplitude (the difference between arterial dilation and constriction); and, (4) venous dilation. Thirty-five patients with ED and 30 male controls were included in the analysis. Mean ± SD age was 52.0 ± 10.8 years in the ED group and 48.1 ± 16.3 years in the control group (p = 0.317). In the dynamic analysis, the arterial dilation was lower in the ED group (1.88 ± 1.50%), as compared with the control group (3.70 ± 1.56%, p < 0.0001). Neither arterial constriction nor venous dilation differed between groups. The reaction amplitude was decreased in ED patients (2.40 ± 2.02%, p = 0.023), compared to controls (4.25 ± 2.20%). In the Pearson correlation analysis, the ED severity, was directly correlated with both reaction amplitude (R = .701, p = 0.004) and arterial dilation (R = .529, p = 0.042). In conclusion, subjects with vasculogenic ED are featured by a significant dysfunction of the retinal neurovascular coupling, which is inversely correlated with ED severity.

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.

INNER AND OUTER CHOROIDAL CHANGES IN THE FELLOW EYE OF PATIENTS WITH UNILATERAL CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To quantitatively evaluate the inner and outer choroidal changes in the fellow eyes of patients with unilateral central serous chorioretinopathy (CSC). METHODS: We analyzed data from patients with a diagnosis of unilateral CSC who had structural optical coherence tomography (OCT) and swept-source OCT angiography obtained. An additional group of age-matched healthy patients was included for comparison. The main outcome measures were: (1) choriocapillaris flow deficits' quantitative metrics; (2) choroidal luminal (LCA) and stromal (SCA) areas; and (3) choroidal vascularity index. RESULTS: Fellow unaffected eyes from 60 patients with unilateral CSC and 30 healthy subjects were included in the analysis. Mean ± SD age was 47.5 ± 9.9 years in the unilateral CSC group and 50.7 ± 10.8 years in the control group (P = 0.410). In the structural OCT assessment, both the LCA and SCA were increased in the unilateral CSC group (0.33 ± 0.11 and 0.29 ± 0.10 mm2) compared with healthy controls (0.28 ± 0.08 and 0.27 ± 0.05 mm2), although only differences in LCA reached a statistical significance (P = 0.041 and P = 0.286 for LCA and SCA, respectively). The choroidal vascularity index was higher in CSC patients (53.7 ± 3.6 and 50.9 ± 5.5%, P = 0.045). In the OCT angiography evaluation, the choriocapillaris flow deficits' percentage and number were increased in those patients affected by unilateral CSC. In multiple regressions, the strongest association with choriocapillaris percentage of flow deficits was with the presence of pachychoroid pigment epitheliopathy signs in the study eye (P < 0.0001). CONCLUSION: Our results corroborate the hypothesis that inner and outer choroidal changes affect both eyes of patients with unilateral disease.

PHOTORECEPTOR OUTER SEGMENT IS EXPANDED IN THE FELLOW EYE OF PATIENTS WITH UNILATERAL CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To quantitatively evaluate the photoreceptor structural changes in the fellow unaffected eyes of patients with unilateral central serous chorioretinopathy (CSC). METHODS: This is a retrospective cross-sectional study. We analyzed data from patients with diagnosis of unilateral CSC, as based on clinical examination and multimodal imaging, who had structural optical coherence tomography obtained. An additional group of age-matched healthy patients was included for comparison. Main outcome measures were as follows: (1) the foveal photoreceptor outer segment lateral surface and (2) the foveal choroidal thickness. RESULTS: One hundred and sixty fellow unaffected eyes of 160 unilateral CSC patients and 50 age-matched controls (50 eyes) were included. The mean ± SD age was 51.6 ± 11.1 years (range 28-80 years) in the unilateral CSC group and 52.8 ± 10.8 years (range 31-74 years) in the control group (P = 0.511). The foveal photoreceptor outer segment lateral surface was significantly increased in the unaffected eyes with CSC in the fellow eye (0.068 ± 0.007 mm2) as compared with control eyes (0.060 ± 0.005 mm2, P < 0.0001). The mean ± SD foveal choroidal thickness was 368.0 ± 105.7 µm in the unilateral CSC group and 302.9 ± 92.2 µm in control patients (P < 0.0001). In the Pearson correlation test, the photoreceptor outer segment lateral surface correlated with the choroidal thickness in the CSC group (R = 0.166, P = 0.016) but not in the control group (R = -0.025, P = 0.864). CONCLUSION: Our results corroborate the hypothesis that retinal and choroidal changes affect both eyes of patients with acute/history of unilateral disease. These structural changes could be intended as an imaging evidence of reduced photoreceptor outer segment turnover secondary to retinal pigment epithelium and choroid dysfunction.