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PurposeTo analyze the quantitative and qualitative early changes of choroidal neovascularization (CNV) associated with chronic central serous chorioretinopathy (CSC) after treatment using optical coherence tomography-angiography (OCT-A).MethodsCharts of consecutive patients with diagnosis of chronic CSC complicated by CNV were retrospectively reviewed. Included patients were divided in photodynamic therapy (PDT) or aflibercept group on the basis of the treatment received (half-fluence PDT or aflibercept 2.0 mg/0.05 ml intravitreal injection). Main outcome measures included the changes between baseline and 1-month follow-up in CNV vessel density (VD) and area on OCT-A images after thresholding and binarization.ResultsA total of 30 eyes of 26 Caucasian patients were included: 17 eyes of 15 patients in PDT group (mean age 53 ± 11 years) and 13 eyes of 11 patients in aflibercept group (mean age 58 ± 8 years [p = 0.196]). In both PDT and aflibercept groups, best-corrected visual acuity improved at 1 month, and central macular thickness and subretinal fluid significantly decreased. VD did not change after the treatment in both groups (p = 0.502 and p = 0.086) although CNV area decreased significantly (from 0.586 ± 0.449 mm2 to 0.553 ± 0.453 mm2 [0.041]) in the PDT group, and nonsignificantly (from 0.767 ± 0.466 mm2 to 0.733 ± 0.472 mm2 [p = 0.095]) in the aflibercept group. The same results were confirmed in the subanalysis of the 18 treatment-naïve eyes.ConclusionsWe demonstrated that, despite all patients showed a favorable clinical response, VD of CNVs complicating chronic CSC did not change after treatment. These findings support the idea that arteriogenesis is the main driving force of CNV in pachychoroid-related macular disorders.

Macular edema (ME) is a major complication of several vascular and inflammatory retinal diseases. Multiple mechanisms are implicated in its development and lead to visual impairment that could be reversible (the acute stages) or not reversible (long-standing ME). For this reason, an effective approach to the treatment of ME is of paramount importance in order to prevent irreversible damage of visual function. In this review, we discuss the management of ME and, in particular, current data of studies and clinical trials about drugs that have already been evaluated or are under investigation in the management of ME. Although several diseases could lead to the development of ME, we focus on the three main causes: diabetic retinopathy (DR), retinal vein occlusion (RVO), and uveitis. The introduction into clinical practice of anti-vascular endothelial growth factor injections (ranibizumab and aflibercept) and dexamethasone implants has revolutionized the treatment of ME secondary to DR and RVO. However, new drugs are needed in the treatment of resistant forms of ME secondary to DR and RVO. A fluocinolone acetonide implant has been approved by the US Food and Drug Administration for the treatment of diabetic ME but not for RVO. Furthermore, brolucizumab and abicipar pegol have been shown to be effective in preliminary studies and have the chance to be approved soon for diabetic ME treatment. In ME secondary to uveitis, a crucial role is played by corticosteroids and non-biologic immunomodulatory drugs. However, several new biologic agents are under investigation in different clinical trials and could be important new therapeutic options in cases with a low response to first-line therapy. However, only a few of these drugs will enter the market after proving their safety and efficacy. Only after that will we be able to offer a new therapeutic option to patients affected by uveitic ME.

PurposeTo characterize the imaging features of blind patients with end-stage inherited retinal degeneration (IRD) and to assess possible morpho-functional correlations.MethodsIn this observational cross-sectional study, we reviewed the clinical data and multimodal imaging of 40 eyes of 21 blind (light perception or less) institutional patients affected by end-stage IRD screened for Alpha AMS (Retina Implant AG, Reutlingen, Germany) retinal prosthesis eligibility. Analysis was carried out using spectral-domain optical coherence tomography (SD-OCT), fluorescein angiography and fundus autofluorescence.ResultsAmong patients with IRD-related low vision, the extrapolated prevalence of the blind was roughly 10%, median age 60.4 years with a disease duration of 40.4 years, showing epiretinal membranes (80%), hyperreflective intraretinal nodules (90%) and the absence of the ellipsoid zone (77.5%) on SD-OCT examination. Cystoid macular oedema was present in 52.5% of eyes, the majority of which being of the microcystoid subtype (42.5%), while 37.5% of eyes also lacked outer and inner retinal layer segmentation. Disease duration was found to be predictive of disrupted retinal layers (P = 0.029) and microcystoid macular oedema (P = 0.035), which was also more frequent in eyes without light perception (P = 0.013).ConclusionsEyes without vision due to end-stage IRD have a typical imaging pattern, predominantly characterized by epiretinal membranes, hyperreflective intraretinal nodules and the absence of the ellipsoid zone. Furthermore, microcystoid macular oedema and retinal layer disruption may be considered as signs of longstanding disease.

Age-related macular degeneration (AMD), the most important cause of vision loss in elderly people, is a degenerative disorder of the central retina with a multifactorial etiopathology. AMD is classified in dry AMD (d-AMD) or neovascular AMD depending on the presence of choroidal neovascularization. Currently, no therapy is approved for geographic atrophy, the late form of d-AMD, because no treatment can restore the damage of retinal pigment epithelium (RPE) or photoreceptors. For this reason, all treatment approaches in d-AMD are only likely to prevent and slow down the progression of existing atrophy. This review focuses on the management of d-AMD and especially on current data about potential targets for therapies evaluated in clinical trials. Numerous examinations are available in clinics to monitor morphological changes in the retina, RPE and choroid of d-AMD patients. Fundus autofluorescence and optical coherence tomography (OCT) are considered the most useful tools in the diagnosis and follow-up of d-AMD alterations, including the monitoring of atrophy area progression. Instead, OCT-angiography is a novel imaging tool that may add further information in patients affected by d-AMD. Several pathways, including oxidative stress, deposits of lipofuscin, chronic inflammation and choroidal blood flow insufficiency, seem to play an important role in the pathogenesis of d-AMD and represent possible targets for new therapies. A great number of treatments for d-AMD are under investigation with promising results in preliminary studies. However, only few of these drugs will enter the market, offering a therapeutic chance to patients affected by the dry form of AMD and help them to preserve a good visual acuity. Further studies with a long-term follow-up would be important to test the real safety and efficacy of drugs under investigation.

Age-related macular degeneration (AMD) is a multifactorial disease and a leading cause of vision impairment in elderly people in Western society. Geographic atrophy (GA), the late stage of dry AMD, is typically defined as a round or oval area of atrophy of 175 µm or more. In GA patients, visual acuity (VA) can still be good if the macula is spared, but decreased if GA extends through the fovea causing a great impairment of quality of life. Because of a poor correlation between VA and GA lesions or progression, a multimodal imaging approach is necessary to better follow up GA patients. In the last years, the introduction in clinical practice of new non-invasive tools such as fundus autofluorescence, structural optical coherence tomography (OCT) and OCT angiography helped the ophthalmologists to better understand the natural course of GA patients. However, several pathways concerning the pathogenesis of the disease are not completely clarified yet and should be investigated further. Although no approved therapy exists for GA, healthy lifestyle and nutritional intervention with some specific supplementations (e.g., vitamins C and E, beta-carotene, high dietary folate) may help to prevent the onset and to delay the progression of the disease. At the same time, several drugs are under evaluation in clinical trials with interesting results. These drugs try to stop several pathways implicated in the pathogenesis of GA, but probably only a few of these will prove truly effective, confirming the preliminary results, and will be available in clinical practice.

This review aims to give to the reader an overview selectively oriented on safety and efficacy of surgery, providing concise and direct answers about crucial questions of trainees and experts. Surgery for idiopathic epiretinal membrane (ERM) is a safe and effective procedure that can achieve long-term stable postoperative visual and anatomical improvement, with an overall low recurrence and complication rate. Young patients, with a short onset of symptoms and with better initial visual acuity achieve higher levels of visual outcome. The preoperative degree of metamorphopsia is the prognostic factor for their postoperative degree. Successful results may be obtained in eyes with specific optical coherence tomography criteria, such as thin ganglion cell layers, thin internal plexiform layer, longer photoreceptors outer segment, regular ellipsoid zone and cone outer segment tips line, and without ectopic inner foveal layer. Internal limiting membrane peeling demonstrates positive anatomical and functional outcomes, but final positions about its safety remain controversial.

PurposeTo investigate the optical coherence tomography (OCT) en face reconstruction of the choroid in different phenotypes of non-neovascular age-related macular degeneration (AMD), to identify the relative distribution of the vascular patterns of the Haller’s layer in each AMD category.MethodsRetrospective study enrolling consecutive patients with non-neovascular AMD. Patients were divided into the following: (1) those with reticular pseudodrusen (RPD); (2) those with small (< 63 μm) or medium–large drusen (63–124 μm); (3) those with geographic atrophy (GA). Qualitative analysis of the en face images provided by CIRRUS HD-OCT 5000 (Carl Zeiss Meditech, Inc., Dublin, USA) was performed, identifying five arrangements of Haller’s vessels: temporal herringbone, branched from below, laterally diagonal, double arcuate, and reticular. Choroidal thickness (CT) was measured from structural OCT. Healthy age-matched subjects were included as a control group.ResultsFifty-eight eyes of 58 patients (20 eyes with RPD; 22 eyes with drusen; 16 eyes with GA) and 18 control eyes were enrolled. The laterally diagonal configuration was the most prevalent (40.0%) in the RPD group; the reticular pattern was the most frequent in the drusen group (50.0%); the double arcuate (62.5%) was the most recurrent pattern in patients with GA. In the control group, the temporal herringbone (38.9%) arrangement was the most represented. The CT associated with the temporal herringbone and reticular arrangement was significantly higher compared to the branched from below (p < 0.001), the laterally diagonal (p = 0.014), and the double arcuate pattern (p = 0.009).ConclusionDifferent phenotypes of non-neovascular AMD present a specific distribution of vascular arrangement on en face OCT. The temporal herringbone and the reticular pattern (the ones more associated in a physiological setting) disclosed a thicker choroid compared to the arrangements more represented in non-neovascular AMD-correlated phenotypes.

PurposeTo compare macular atrophy (MA) secondary to age-related macular degeneration (AMD) and Stargardt disease (STGD) using the choroidal vascularity index (CVI).MethodsIn this multicentric retrospective study, two distinct cohorts were collected: patients with MA secondary to AMD and MA secondary to STGD. All patients were investigated using a multimodal imaging approach, including CVI in the subfoveal 1000 μm area. Of note, the CVI is not influenced by aging, which allows comparisons between different cohorts.ResultsSeventy eyes were included: 35 eyes of 35 patients (mean age 78 ± 7 years) in the AMD group and 35 eyes of 35 patients (mean age 41 ± 16 years, p < 0.001) in the STGD group. Choroidal thickness was significantly lower in the AMD group in comparison to the STGD group (151 ± 80 μm vs 353 ± 105 μm, p < 0.001). The total choroidal area (TCA) was significantly greater in the STGD group in comparison to the AMD group (1.734 ± 0.958 mm2 vs 0.538 ± 0.391 mm2, respectively, p < 0.001).Interestingly, the CVI was significantly lower in AMD patients in comparison to STGD patients (27.322 ± 15.320% vs 49.880 ± 7.217%, respectively, p < 0.001), and this difference was confirmed in the subgroup of patients over 50 years old.ConclusionOur results corroborate the hypothesis that large choroidal vessels were impaired to a greater extent in AMD than in STGD. CVI may help in differentiating AMD from STGD in the presence of MA, better understanding of the pathogenesis, and monitoring of therapeutic response.

Purpose To compare two commercially available staining solutions (MembraneBlue Dual® by D.O.R.C., Netherlands, and TWIN by AL.CHI.MI.A. S.R.L., Italy), in terms of intraoperative handling, staining efficacy and safety, in eyes undergoing surgery for idiopathic epiretinal membrane (ERM). Methods In this observational cross-sectional study, the performance of the dyes used during the procedure (cohesion, ERM and internal limiting membrane [ILM] staining efficacy) was scored by the surgeon using a customized questionnaire after 10 procedures with each of the two dyes. Best-corrected visual acuity (BCVA), central foveal thickness (CFT), blue-light fundus autofluorescence (BAF), and microperimetry-determined retinal sensitivity were reviewed preoperatively and then at 1 and 3 months after surgery. Results ILM staining efficacy with TWIN was scored 2.89 ± 0.33 by the surgeons, which turned out to be higher than with MembraneBlue Dual® (1.90 ± 0.31, P  = 0.0002). The cohesion score was 2.70 ± 0.48 for TWIN and resulted significantly higher than with MembraneBlue Dual® (1.60 ± 0.51, P  = 0.0010). BCVA, CFT and retinal sensitivity were similar in the two groups, 1 and 3 months postoperatively ( P nonsignificant for all). Conclusions Both TWIN and MembraneBlue Dual® dyes showed suitable staining properties and equivalent safety and efficacy profiles, both intra- and postoperatively. The TWIN dye might offer a solution for surgeons who prefer a more cohesive and stable dye.

Purpose To assess the rate of occurrence and the risk factors of postsurgical macular edema (PSME) in eyes with idiopathic epiretinal membrane (iERM) or full-thickness macular hole (FTMH). Methods Retrospective longitudinal analysis of all subjects scheduled for vitrectomy with or without combined cataract surgery over a 6-month period. Electronic medical charts and imaging data were analyzed preoperatively and at 1, 3 and 6 months after surgery. Results From 101 patients diagnosed with iERM or FTMH, 71 patients were eligible for the study. Forty-nine eyes with iERM (69.0%) and 22 eyes with FTMH (31.0%) underwent vitrectomy either isolated (31.0%) or combined with cataract extraction (69.0%). The overall rate of PSME was 26.7%, without differences between the two groups ( P  = 0.9479). Combined cataract extraction did not affect the overall occurrence of PSME rate in both groups ( P  = 0.9255 in FTMH and P  = 0.8658 in iERM). If grouped by stage, eyes with stage 4 iERM though disclosed an increased rate of PSME (57.1%) compared to lower (1 to 3) stages (14.3%, P  = 0.0021), particularly when combined with cataract surgery (71.4% vs. 15.4% in stages ≤ 3, P  = 0.0021). The PSME odds ratio for a stage 4 iERM is 8 (95% CI: 1.933–33.1; P  = 0.0041) compared to stages 3 and below. Conclusions PSME remains a clinically relevant and frequent event after surgery for iERM and FTMH. Patients with stage 4 iERM have an 8-fold higher likelihood of developing PSME in a 6-month postsurgical period compared to iERM in 1–3 stages, especially when combined with cataract extraction.