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Abstract Introduction Macular neovascularization (MNV) secondary to age-related macular degeneration (AMD) is well managed by anti-vascular endothelial growth factor (anti-VEGF) intravitreal injections. However, outer retinal atrophy represents an unavoidable occurrence detected during follow-up. Several imaging metrics have been proposed as clinically relevant in stratifying the risk of onset of outer retinal atrophy. The main goal of this study is to evaluate the impact of noninvasive imaging metrics on the assessment of outer retinal atrophy onset in a large cohort of eyes with neovascular AMD managed in a real-world setting. Methods This study was a prospective, observational, case series. We included patients affected by newly diagnosed neovascular AMD, requiring anti-VEGF intravitreal injections. We collected clinical and imaging data, with a planned follow-up of 24 months. The multimodal imaging protocol included optical coherence tomography, optical coherence tomography angiography, and fundus autofluorescence. We collected noninvasive imaging metrics and we assessed the relationship with the morphological and functional outcome evaluated at 12-month and 24-month time points. Results We included 370 eyes of 370 patients with exudative AMD (210 male; mean age 79 ± 8 years). MNV were classified as follows: type 1, 198 (54%); type 2, 89 (24%); polypoidal choroidal vasculopathy, 29 (7%); and type 3, 54 (15%). A total of 120 out of 370 eyes (33%) showed complete outer retinal atrophy at the end of the 2-year follow-up. The presence of intraretinal fluid, thinning of the Sattler choroidal layer, late anti-VEGF switch, the overall number of anti-VEGF injections, and the perfusion characteristics of the MNV were found to be the most relevant factors associated with the onset of outer retinal atrophy. The other collected metrics were found to be less clinically relevant, also showing no cumulative effect in the multivariate analysis (p > 0.05). Conclusions We identified imaging metrics significantly associated with the 2-year risk onset of outer retinal atrophy. These metrics might pave the way for the development of future customized anti-VEGF treatment strategies.

Abstract Introduction Foveal eversion (FE) is a recently described optical coherence tomography (OCT) finding associated with negative outcome in diabetic macular edema. The main goal of the present study was to investigate the role of the FE metric in the diagnostic workup of retinal vein occlusion (RVO). Methods This study was a retrospective, observational case series. We included 168 eyes (168 patients) affected by central RVO (CRVO) and 116 eyes (116 patients) affected by branch (RVO). We collected clinical and imaging data from CRVO and BRVO eyes affected by macular edema with a minimum follow-up of 12 months. On structural OCT, we classified FE as pattern 1a, characterized by thick vertical intraretinal columns, pattern 1b, presenting thin vertical intraretinal lines, and pattern 2, showing no signs of vertical lines in the context of the cystoid macular edema. For statistical purposes, we considered data collected at baseline, after 1 year and at the last follow-up. Results The mean follow-up was 40 ± 25 months for CRVO eyes and 36 ± 24 months for BRVO eyes. We found FE in 64 of 168 CRVO eyes (38%) and in 25 of 116 BRVO eyes (22%). Most of the eyes developed FE during the follow-up. For CRVO eyes, we found 6 eyes (9%) with pattern 1a, 17 eyes (26%) with pattern 1b and 41 eyes (65%) with pattern 2. Of those BRVO eyes with FE, we found 8 eyes (32%) with pattern 1a + 1b and 17 eyes (68%) with pattern 2. In both CRVO and BRVO the presence of FE was significantly associated with higher persistence of macular edema and worse outcome, with FE pattern 2 representing the most severe condition. Remarkably, FE patterns 1a and 1b were characterized by BCVA stability over the follow-up, whereas FE pattern 2 showed significant bestcorrected visual acuity (BCVA) worsening at the end of the follow-up. Conclusions FE can be considered a negative prognostic biomarker in RVO, associated with higher persistence of macular edema and worse visual outcome. Müller cell impairment might represent the pathogenic mechanism leading to the loss of macular structural support and impairment of fluid homeostasis.

Purpose: To analyze fixation location and stability in best vitelliform macular dystrophy (BVMD) and test their association with best-corrected visual acuity (BCVA). Design: Observational, cross-sectional study. Participants: Thirty patients (55 eyes) affected by genetically confirmed BVMD were followed up at the Retinal Heredodystrophies Unit of IRCCS San Raffaele Scientific Institute, Milan. Methods: Patients underwent testing with macular integrity assessment (MAIA) microperimeter. Fixation location was measured as distance in degrees (°) between preferred retinal locus (PRL) and estimated fovea location (EFL); fixation was defined as eccentric when the distance between PRL and EFL exceeded 2°. Fixation stability was graded as stable, relatively unstable, or unstable and expressed as bivariate contour ellipse area (BCEA, °2). Main Outcome Measures: Fixation location and stability. Results: The median distance of the PRL from the anatomic fovea was 0.7°, and fixation location was eccentric in 27% of eyes. Fixation was graded as stable in 64% of eyes, relatively unstable in 13%, and unstable in 24%, with a median 95% BCEA of 6.2°2. The atrophic/fibrotic stage was associated with worse fixation parameters (all P

Abstract To compare clinical and imaging characteristics of extensive macular atrophy with pseudodrusen-like appearance (EMAP) versus diffuse-trickling geographic atrophy (DTGA) and non-diffuse-trickling geographic atrophy (nDTGA) phenotypes of age-related macular degeneration. Prospective, observational study performed in the Ophthalmology Department of IRCCS San Raffaele Hospital between January 2015 and January 2021. Patients examination included fundus autofluorescence (FAF) and optical coherence tomography at baseline and follow-up visits. We measured subfoveal choroidal thickness (SCT), Sattler/choroid ratio (SCR), choroidal vascularity index and ellipsoid zone disruption distance on OCT scans. We calculated progression rates and circularity of the atrophic lesions on FAF images. These variables were compared between the three groups and correlations with progression rates and visual acuity were assessed. Sixty-three eyes from 63 patients were included: 18 with EMAP, 18 with DTGA and 27 with nDTGA. Mean follow-up was 3.73 ± 2.12 years. EMAP and DTGA shared a faster progression, lower circularity and SCR, and higher EZ disruption distance than nDTGA, while SCT and CVI were similar between the three groups. Baseline circularity and SCR correlated with progression rates. EMAP and DTGA show similar OCT and FAF characteristics, which differ from nDTGA.

Abstract Introduction Photobiomodulation (PBM) represents a potential treatment for non-exudative age-related macular degeneration (AMD). PBM uses wavelengths of light to target components of the mitochondrial respiratory chain to improve cellular bioenergetic outputs. The aim of this study was to further investigate the effects of PBM on clinical, quality of life (QoL) and anatomical outcomes in subjects with intermediate stage non-exudative AMD. Methods The multicenter LIGHTSITE II study was a randomized clinical trial evaluating safety and efficacy of PBM in intermediate non-exudative AMD. The LumiThera Valeda® Light Delivery System delivered multiwavelength PBM (590, 660 and 850 nm) or sham treatment 3 × per week over 3–4 weeks (9 treatments per series) with repeated treatments at baseline (BL), 4 and 8 months. Subjects were enrolled with 20/32 to 20/100 best-corrected visual acuity (BCVA) and no central geographic atrophy (GA) within the central fovea (500 μm). Results LIGHTSITE II enrolled 44 non-exudative AMD subjects (53 eyes). PBM-treated eyes showed statistically significant improvement in BCVA at 9 months (n = 32 eyes, p = 0.02) with a 4-letter gain in the PBM-treated group versus a 0.5-letter gain in the sham-treated group (ns, p

Abstract The aim of the study was to characterize macular edema (ME) in retinitis pigmentosa (RP) by means of quantitative optical coherence tomography (OCT)-based imaging. The study was designed as observational, prospective case series, with 1-year follow-up. All RP patients underwent complete ophthalmologic assessment, including structural OCT, OCT angiography, and microperimetry (MP). The primary outcome was the characterization through quantitative OCT-based imaging of RP eyes complicated by ME. A total of 68 RP patients’ eyes (68 patients) and 68 eyes of 68 healthy controls were recruited. Mean BCVA was 0.14 ± 0.17 LogMAR at baseline and 0.18 ± 0.23 LogMAR at 1-year follow-up (p > 0.05). Thirty-four eyes (17 patients; 25%) showed ME, with a mean ME duration of 8 ± 2 months. Most of the eyes were characterized by recurrent ME. The ME was mainly localized in the inner nuclear layer in all eyes. LogMAR BCVA was similar in all RP eyes, whether with or without ME, although those with ME were associated with higher vessel density values, as well as thicker choroidal layers, than those without ME. In conclusion, the inner retina is closely involved in the pathogenesis of ME. The impairment of retinal-choroidal exchanges and Müller cell disruption might be a major pathogenic factor leading to the onset of ME in RP.

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Abstract The aim of the present study was to describe foveal eversion patterns in diabetic macular edema (DME) and to assess their relationship with the course of the disease and the outcome. The study was designed as prospective, observational, with two years of follow-up. DME patients were divided in two groups, one treated by combined anti-VEGF injections and dexamethasone (DEX) implants, and the other treated by fluocinolone acetonide (FAc) implant with additional anti-VEGF retreatments if needed. Main outcome measures were foveal eversion prevalence, foveal eversion patterns, best-corrected visual acuity (BCVA), central macular thickness (CMT), structural OCT metrics, number of intravitreal injections. One hundred and forty-six eyes (146 patients; 80 males; mean age 67 ± 8 years) affected by already treated DME, with 84 eyes treated with anti-VEGF/DEX treatments (mean of 10 ± 3 injections) and 62 treated with FAc implant. Looking at the treatments administered before the inclusion into the study, 84 eyes (58%) were treated with anti-VEGF injections, whereas 62 eyes (42%) underwent a combination of anti-VEGF and corticosteroids implants. DME eyes showed statistically significant improvements of LogMAR BCVA and CMT over the 2-year follow-up. Foveal eversion was found in 83 eyes (57%), categorized as follows: Pattern 1a (16;19%); Pattern 1b (22;27%) and Pattern 2 (45;54%). BCVA improvement was detected in all the subgroups, excepting for Pattern 2, which showed also significantly worse structural OCT parameters. Pattern 1b and Pattern 2 were characterized by significantly higher prevalence of persistent DME (64% and 89% of cases, respectively). Foveal eversion patterns were correlated with progressively worse DME outcome. Foveal eversion may be associated to the loss of foveal homeostasis, with consequent poor response to intravitreal treatments and worse DME outcome.

Purpose: To identify the vascular biomarkers of peripheral capillary nonperfusion in patients affected by naive central retinal vein occlusion (CRVO), and to analyze their changes over the follow-up. Study Design: Consecutive prospective case series with a planned follow-up of 2 years. Participants: Thirty-five patients affected by CRVO and 35 healthy gender- and age-matched subjects were enrolled in the study. Methods: Ophthalmic examination included best corrected visual acuity (BCVA), ultrawidefield fluorescein angiography (UWFFA), OCT, and OCT angiography (OCTA). Main Outcome Measures: Vessel density (VD) at the superficial capillary plexus and deep capillary plexus (DCP) were calculated on OCTA images. The ischemic index (ISI) was calculated on UWFFA. Results: The mean baseline ISI was 37%, increasing to 40% at the end of the follow-up, whereas it was 4.9% in the patients’ fellow eyes and 4.5% in the control group with no change over the follow-up. OCT angiography revealed VD reduction in the DCP, considering both 3 × 3 mm and 12 × 12 mm scans. The correlation analyses revealed that DCP VD was the only parameter showing a statistically significant correlation with the foveal avascular zone (FAZ) area, BCVA, and ISI. Conclusions: Deep capillary plexus VD impairment is detectable in all CRVO cases, variably involving both the central retina (with enlarged FAZ) and the periphery (with VD reduction in the peripheral retina). The severity of DCP VD reduction has correlates with various clinical markers. Deep capillary plexus VD may represent a crucial biomarker to characterize CRVO, and further studies are necessary to identify the cutoff thresholds for the different clinical manifestations. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Background: Newer generation ophthalmologists practicing in the developed world are not very familiar with some tropical ocular diseases due to the absence of reports in the ophthalmic literature over the past thirty years. Because of world globalization or due to influx of immigrants from sub-Saharan Africa, exotic retinal diseases are being encountered more often in ophthalmology clinics. Methods: A multicenter case series of chorioretinitis or optic neuritis with obscure etiology that used serial multimodal imaging. Results: Four cases qualified with the diagnosis of presumed ocular onchocerciasis based on their residence near fast rivers in endemic areas, multimodal imaging, long term follow-up showing progressive disease and negative workup for other diseases. Characteristic findings include peripapillary choroiditis with optic neuritis or atrophy, subretinal tracts of the microfilaria, progressive RPE atrophy around heavily pigmented multifocal chorioretinal lesions of varying shapes, subretinal white or crystalline dots, and response to ivermectin. Typical skin findings are often absent in such patients with chorioretinitis rendering the diagnosis more challenging. Conclusions: Familiarity with the myriad ocular findings of onchocerciasis, and a high-degree of suspicion in subjects residing in endemic areas can help in the correct diagnosis and implementation of appropriate therapy. Onchocercal chorioretinitis is a slow, insidious, progressive, and prolonged polymorphous disease.

Proliferative diabetic retinopathy (PDR) poses a significant therapeutic problem that often results in severe visual loss. Panretinal photocoagulation (PRP) has long been a mainstay treatment for this condition. Conversely, intravitreal anti-VEGF therapy has served as an alternative treatment for PDR. This review aimed to evaluate the effects of PRP combined with anti-VEGF therapy on the regression of neovascularization (NV), including functional outcomes and incidence of complications. The MEDLINE database was searched for articles evaluating regression of NV using a combination of the following terms: “proliferative diabetic retinopathy”, “anti-VEGF”, “panretinal photocoagulation”, and “combined treatment”. The search yielded a total of 22 articles. The analysis of their results indicated PRP combined with ant-VEGF therapy as superior over PRP alone in the management of PDR. Combination treatment yields better and faster regression of NV and a lower incidence of serious complications, such as vitreous hemorrhage and the need for pars plana vitrectomy. Nevertheless, complete regression of NV is not achieved in a significant proportion of patients. Further research is needed to establish the most effective schedule for intravitreal injections as an adjunct to PRP. The current literature shows that in some cases, cessation of anti-VEGF injection in combination treatment for PDR can lead to relapse of NV.

Abstract The objective of this prospective study was to investigate the morphological changes of myopic choroidal neovascularization (mCNV) after treatment with anti-vascular endothelial growth factor and to identify potential features predictive of the final BCVA. OCT and OCTA features were evaluated at baseline and at 1, 6 and 12 months. Parameters investigated were the maturity pattern, presence of mCNV OCT activity signs, subretinal fibrosis and mCNV area. Forty patients (41 eyes) were included in the study. At the final visit, after a mean of 3.1 ± 1.4 injections, BCVA had improved significantly (p = 0.009) and subretinal hyperreflective exudation, subretinal fluid and intraretinal cysts nearly disappeared at 12 months. At baseline, 20 eyes had an immature CNV that were smaller, required less injections (2.5 ± 1.2 vs 3.8 ± 1.4, p = 0.002), they completely regressed in seven eyes and achieved a better BCVA (0.14 ± 0.15 vs 0.40 ± 0.26 logMAR, p

Background: Leber congenital amaurosis is the first form of inherited retinal dystrophy (IRD) treated with a gene therapy approach using voretigene neparvovec (VN). To date, 42 patients have been treated, 25 of whom, treated at Clinica Oculistica Vanvitelli (Naples), have shown – after 45 days of treatment – a significant increase in dim-light visual function, a widening of the visual field, and an increase in central visual acuity. Objective: A workshop has been organized to foster rapid access, investigate the current organizational scenario, and identify a value framework suitable for making gene therapy delivery efficient in terms of efficacy, safety, and sustainability. Methods: The workshop involved 14 experts in clinical genetics, ophthalmology, and vitreoretinal surgery. All experts were subjected to questions related to three topics: diagnostic-therapeutic pathway of IRD patients, essential requirements for gene therapy delivery centres, and standardized model for therapy delivery. All contributions were judged to be of equal value. Results: The panel identified: the steps of the diagnostic pathway to achieve early diagnosis; the essential criteria that delivery centres must possess in terms of experience, multidisciplinary team, and technical equipment; a standardized model for VN administration. A network of few centres was identified as the best organizational model for VN delivery since it would ensure the gaining of experience and clinical excellence. Conclusion: This paper provides a perspective that can be used as a starting point to standardize the diagnostic-therapeutic pathway of IRD patients and define the essential requirements that centres must meet for VN administration.

Capillary non-perfusion (CNP) is one of the key hallmarks of diabetic retinopathy (DR), which may develop both in the periphery and at the posterior pole. Our perspectives on CNP have extended with the introduction of optical coherence tomography angiography (OCTA) and ultra-widefield imaging, and the clinical consequences of peripheral and macular CNP have been well characterized. Fluorescein angiography (FA) continues to be the gold standard for detecting and measuring CNP, particularly when ultra-widefield imaging is available. OCTA, on the other hand, is a quicker, non-invasive approach that allows for a three-dimensional examination of CNP and may soon be regarded as an useful alternative to FA. In this review, we provide an updated scenario regarding the characteristics, clinical impact, and management of central and peripheral CNP in DR.

Abstract Optical coherence tomography angiography (OCTA) provides several data regarding the status of retinal capillaries. This information can be further enlarged by employing quantitative metrics, such as vessel density (VD). A mandatory preliminary step of OCTA quantification is image binarization, a procedure used to highlight retinal capillaries on empty background. Although several binarization thresholds exist, no consensus is reached about the thresholding technique to be used. In this study, we tested thirteen binarization thresholds on a dataset made by thirty volunteers. The aim was to assess the impact of binarization techniques on: (I) detection of retinal capillaries, assessed by the calculation of overlapping percentages between binarized and original images; (II) quantitative OCTA metrics, including VD, vessel tortuosity (VT) and vessel dispersion (Vdisp); (III) foveal avascular zone (FAZ) detection. Our findings showed Huang, Li, Mean and Percentile as highly reliable binarization thresholds (p

Abstract Outer retinal tubulations (ORT) are a relatively new finding characterizing outer retinal atrophy. The main aim of the present study was to describe ORT development in advanced age-related macular degeneration (AMD) and to assess its relationship with disease’s severity. Patients with advanced AMD characterized either by macular neovascularization or geographic atrophy, showing signs of outer retinal disruption or retinal pigment epithelium atrophy on structural optical coherence tomography (OCT) at the inclusion examination were prospectively recruited. All the patients underwent complete ophthalmologic evaluation, structural OCT scans and fundus autofluorescence imaging. The planned follow-up was of 3-years. Main outcome measures were ORT prevalence, mechanism of ORT formation, mean time needed for complete ORT formation, best-corrected visual acuity (BCVA), definitely decreased autofluorescence (DDAF) area, questionably decreased autofluorescence (QDAF) area, retinal layer thickness, foveal sparing, number of intravitreal injections. We also assessed the possible role of external limiting membrane (ELM) and Müller cells in ORT pathogenesis. Seventy eyes (70 patients) were included; 43 showed dry AMD evolving to geographic atrophy, while 27 displayed the features of wet AMD. Baseline BCVA was 0.5 ± 0.5 LogMAR, decreasing to 0.9 ± 0.5 LogMAR at the 3-year follow-up (p

Background: This report describes the study design and baseline characteristics of patients with Stargardt disease (STGD1) enrolled in the STArgardt Remofuscin Treatment Trial (STARTT). Methods: In total, 87 patients with genetically confirmed STGD1 were randomized in a double-masked, placebo-controlled proof of concept trial to evaluate the safety and efficacy of 20 milligram oral remofuscin for 24 months. The primary outcome measure is change in mean quantitative autofluorescence value of an 8-segment ring centred on the fovea (qAF8). Secondary efficacy variables are best corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), mesopic microperimetry (mMP), spectral domain optical coherence tomography (SD-OCT), reading speed on Radner reading charts, and patient-reported visual function as assessed by the National Eye Institute Visual Functioning Questionnaire 25 (NEI VFQ-25) and Functional Reading Independence (FRI) Index. Results: Mean age of participants was 35±11 years with 49 (56%) female. Median qAF8 value was 438 Units (range 210-729). Median BCVA and LLVA in decimal units were 0.50 (range 0.13-0.80) and 0.20 (range 0.06-0.63), respectively. The median of the mean retinal sensitivity with mMP was 20.4 dB (range 0.0-28.8). SD-OCT showed median central subfield retinal thickness of 142 µm (range 72-265) and median macular volume of 1.65 mm3 (range 1.13-2.19). Compared to persons without vision impairment, both reading performance and patient-reported visual function were significantly lower (p

Diabetic retinopathy (DR) is the most common complication of diabetes and has been historically regarded as a microangiopathic disease. Now, the paradigm is shifting toward a more comprehensive view of diabetic retinal disease (DRD) as a tissue-specific neurovascular complication, in which persistently high glycemia causes not only microvascular damage and ischemia but also intraretinal inflammation and neuronal degeneration. Despite the increasing knowledge on the pathogenic pathways involved in DR, currently approved treatments are focused only on its late-stage vasculopathic complications, and a single molecular target, vascular endothelial growth factor (VEGF), has been extensively studied, leading to drug development and approval. In this review, we discuss the state of the art of research on neuroinflammation and neurodegeneration in diabetes, with a focus on pathophysiological studies on human subjects, in vivo imaging biomarkers, and clinical trials on novel therapeutic options.

Abstract Optical coherence tomography (OCT) angiography (OCTA) is a non-invasive tool for the in-vivo study of the intraretinal vascular network. It is based on the analysis of motion particles within the retina to reconstruct the paths followed by the erythrocytes, i.e. retinal capillaries. To date, qualitative and quantitative information are based on the morphological features disclosed by retinal capillaries. In the present study, we proposed new quantitative functional metrics, named Total Flow Intensity (TFI), Active Flow Intensity (AFI), and Volume-related Flow Intensity (VFI), based on the processing of the blood flow signal detected by OCTA. We studied these metrics in a cohort of healthy subjects, and we assessed their clinical utility by including a cohort of age-matched patients affected by Stargardt disease. Moreover, we compared TFI, AFI, and VFI to the widely used vessel density (VD) parameter. TFI, AFI, and VFI were able to describe in detail the different properties of the retinal vascular compartment. In particular, TFI was intended as the overall amount of volumetric retinal blood flow. AFI represented a selective measure of voxels disclosing blood flow signal. VFI was developed to put in relationship the volumetric blood flow information with the not vascularized retinal volume. In conclusion, TFI, AFI, and VFI were proposed as feasible functional OCTA biomarkers based on the analysis of retinal blood flow signal.

Purpose: Occult Macular Dystrophy (OMD) is an autosomal dominant inherited retinal dystrophy caused by mutations in the retinitis pigmentosa 1-like 1 (RP1L1) gene. The present study describes a novel RP1L1 variant, identified for the first time in two Italian sisters diagnosed with OMD, along with multimodal imaging features, including Optical Coherence Tomography (OCT) Angiography. Methods: We performed multimodal imaging including spectral-domain OCT, blue light autofluorescence (BAF), infrared autofluorescence (IRAF), swept-source OCT Angiography (OCTA), full-field and multifocal electroretinography. Genetic analysis was performed using Next-Generation Sequencing. Pathogenic potential of nonsynonymous novel variants was scored with two in silico algorithms. Results: Proband 1 (P1) and proband 2 (P2) were two Italian sisters of 61 and 56 years old. Both reported a history of progressive visual loss without fundoscopic alterations. P1 reported a 4-year history of rapid visual function worsening, and her best-corrected visual acuity (BCVA) was counting fingers in both eyes. P2 reported a 20-year history of mild but progressive visual acuity loss, and her BCVA was 1/10 and 2/10 respectively in her right and left eye. Structural OCT displayed disorganization of outer retinal bands at the macula and foveal cavitation; loss of foveal photoreceptors was remarkably evident on en-face OCT slabs. OCTA quantitative analysis found that vessel density was reduced both at SCP and DCP while choriocapillaris blood flow was relatively spared. Genetic analysis found the same rare dominant c.2873G > C, p.Arg958Pro variant in the RP1L1 gene. The substitution was regarded as moderately radical according to Grantham score while PolyPhen2 classified the amino acidic substitution as probably damaging. Conclusions and importance: Our study expands the mutational spectrum of RP1L1 gene: the rare c.2873G > C, p.Arg958Pro missense variant may be considered a new pathogenic variant for OMD, the first to be identified exclusively in an Italian family. Moreover, our quantitative OCTA data suggest that OMD is characterized by a rarefaction of superficial and deep capillary plexus.

Background: To investigate optical coherence tomography angiography (OCTA) quantitative parameters associated with macular neovascularization (MNV) size modifications in age-related macular degeneration.Methods: Study design was prospective, with 1-year of follow-up. All the included MNV eyes were treated by anti-VEGF intravitreal injections. Quantitative OCTA parameters, including MNV vessel tortuosity (VT) and MNV reflectivity, were calculated. Post-hoc analyses assessed the correlation between quantitative OCTA metrics and MNV size modifications.Results: A total of 28 MNV eyes of 28 patients were included. Baseline LogMAR BCVA was 0.36 ± 0.21 LogMAR, improved to 0.28 ± 0.22 Log-MAR after 1-year (p < 0.01), with a mean number of 8 ± 3 anti-VEGF injections. Eyes characterized by high MNV VT values group showed worse outcome and higher increases of MNV size. A mean MNV reflectivity value of 101 was associated with a high probability of changes in MNV size. MNV growth was also influenced by the type of MNV, with type 2 and mixed type lesions showing increases in MNV size, unlike type 1 MNV. These factors showed a cumulative effect in determining MNV size modifications. In most of the cases, we observed MNV size increases. Conversely, MNV lesions characterized by low MNV VT values may experience size reductions over the follow-up (34% of cases). The number of intravitreal injections had no significant influence on MNV size changes.Conclusions: Quantitative OCTA allowed to discriminate highly perfused MNV lesions, providing a basis to predict MNV size modifications and the direction of MNV expansion.

Abstract To assess the optical coherence tomography (OCT) features of the repair tissue after retinal pigment epithelial (RPE) tear in neovascular age-related macular degeneration. Retrospective, observational study. Medical and imaging records of patients that developed tears after starting anti-VEGF treatment and with at least 12 months of follow-up were reviewed. OCT reflectivity of the RPE-subretinal hyperreflective tissue (SHT) complex was measured at 6, 12 and 18 months (when available). Reflectivity of the adjacent unaffected RPE-Bruch’s membrane was taken as internal reference. Other variables: grade and rip occurrence (early/late); number of intravitreal injections; type of macular neovascularization; sub-macular hemorrhage (SMH) at onset. Forty-nine eyes (age: 76.1 ± 7.0 years; VA: 0.54 ± 0.27 LogMAR) were included. Thirty-eight eyes had OCT signs of healing during the follow-up, with 21 showing SMH at baseline. Final VA positively correlated with the number of injections and negatively correlated with the RPE-SHT reflectivity and the presence of SMH (p

Aim of the study: To report optical coherence tomography angiography (OCTA) findings in patients affected by CRB1-associated retinal dystrophies. Method: Patients affected by a genetically confirmed CRB1-associated retinal dystrophy were prospectively enrolled in an observational study, along with age- and sex-matched healthy volunteers as control subjects. All study and control subjects received a complete ophthalmic examination and multimodal retinal imaging, including OCTA. Result: A total of 12 eyes from 6 patients were included in the study. The mean BCVA of patients was 0.42 ± 0.25 logMAR. Two patients showed large central atrophy, with corresponding definite hypo-autofluorescence on fundus autofluorescence (FAF). Another four patients disclosed different degrees of RPE mottling, with uneven FAF. On OCTA, the macular deep capillary plexus and choriocapillaris had a lower vessel density in eyes affected by CRB1-associated retinopathy when compared to healthy controls. On the other hand, vessel density at the peripapillary radial capillary plexus, superficial capillary plexus, and deep capillary plexus was significantly altered with respect to control eyes. Statistical analyses disclosed a negative correlation between the deep capillary plexus and both LogMAR best corrected visual acuity and central retinal thickness. Conclusion: Our study reveals that CRB1-associated retinal dystrophies are characterized by vascular alterations both in the macular and peripapillary region, as assessed by OCTA.

Abstract Inherited retinal dystrophies (IRD) are a heterogeneous group of rare chronic disorders caused by genetically determined degeneration of photoreceptors and retinal pigment epithelium cells. Ultra-widefield (UWF) imaging is a useful diagnostic tool for evaluating retinal integrity in IRD, including Stargardt disease, retinitis pigmentosa, cone dystrophies, and Best vitelliform dystrophy. Color or pseudocolor and fundus autofluorescence images obtained with UWF provide previously unavailable information on the retinal periphery, which correlates well with visual field measurement or electroretinogram. Despite unavoidable artifacts of the UWF device, the feasibility of investigations in infants and in patients with poor fixation makes UWF imaging a precious resource in the diagnostic armamentarium for IRD.

Purpose: Sclerochoroidal calcifications (SCC) are rare conditions characterized by unifocal or multifocal well-defined scleral deposits of calcium. The present study describes two cases of SCC complicated by the onset of choroidal neovascularization (CNV). Method: Five patients affected by SCC were enrolled in the study and two cases were complicated by CNV. Both patients underwent complete ophthalmic examination with multimodal imaging including optical coherence tomography angiography (OCTA). Results: In the two patients with CNV (1 male), BCVA was 20/40 and 20/50 in the affected eyes. Fundus examination revealed an irregular yellow-white lesion close to the superotemporal arcade in both patients, with exudation. The diagnosis of CNV was performed by means of fluorescein angiography in one patient and OCTA in the other patient. The patients received a total of 3 and 9 ranibizumab injections respectively over a six-year follow-up, reaching a final BCVA of 20/25 in both patients with stabilization of the CNV. Conclusions: SCC may be complicated by CNV, with good management obtained by intravitreal anti-VEGF injections.

Background: Glaucoma is a chronic, vision-threatening disease, and a major cause of legal blindness. The current view is no longer limited to the progressive optic nerve injury, since growing evidence strongly support the interpretation of glaucoma as a complex neurodegenerative disease. However, the precise pathogenic mechanisms leading to the onset and progression of central nervous system (CNS) impairment, and the functional consequences of this damage, are still partially understood. The main aim of this review is to provide a complete and updated overview of the current knowledge regarding the CNS involvement in glaucoma, and the possible therapeutic perspectives.Methods: We made a careful survey of the current literature reporting all the relevant findings related to the cognitive dysfunctions occurring in glaucoma, with specific remarks dedicated on the higher-order visual function impairment and the possible employment of neuroprotective agents.Results: The current literature strongly support the interpretation of glaucoma as a multifaceted chronic neurodegenerative disease, widely affecting the CNS. The cognitive impairment may vary in terms of higher-order functions involvement and in the severity of the degeneration. Although several neuroprotective agents are currently available, the development of new molecules represents a major topic of investigation for future clinical trials.Conclusions: Glaucoma earned the right to be fully considered a neurodegenerative disease. Glaucomatous patients may experience a heterogeneous set of visual and cognitive symptoms, progressively deteriorating the quality of life. Neuroprotection is nowadays a necessary therapeutic goal and a future promising way to preserve visual and cognitive functions, thus improving patients’ quality of life.

Background: Gene therapy cannot be yet considered a far perspective, but a tangible therapeutic option in the field of retinal diseases. Although still confined in experimental settings, the preliminary results are promising and provide an overall scenario suggesting that we are not so far from the application of gene therapy in clinical settings. The main aim of this review is to provide a complete and updated overview of the current state of the art and of the future perspectives of gene therapy applied on retinal diseases.Methods: We carefully revised the entire literature to report all the relevant findings related to the experimental procedures and the future scenarios of gene therapy applied in retinal diseases. A clinical background and a detailed description of the genetic features of each retinal disease included are also reported.Results: The current literature strongly support the hope of gene therapy options developed for retinal diseases. Although being considered in advanced stages of investigation for some retinal diseases, such as choroideremia (CHM), retinitis pigmentosa (RP), and Leber's congenital amaurosis (LCA), gene therapy is still quite far from a tangible application in clinical practice for other retinal diseases.Conclusions: Gene therapy is an extremely promising therapeutic tool for retinal diseases. The experimental data reported in this review offer a strong hope that gene therapy will be effectively available in clinical practice in the next years.

Background: The aim was to study the relationship between quantitative information provided by optical coherence tomography (OCT) angiography (OCTA) and conventional angiography in macular neovascularization (MNV) secondary to age-related macular degeneration (AMD).Methods: The research was designed as an interventional, prospective study. We included 66 eyes (66 patients) affected by naïve MNV. Multimodal imaging included structural OCT, OCTA, fluorescein angiography (FA), and indocyanine green angiography (ICGA). The follow-up lasted 1 year. Patients were treated by PRN anti-VEGF injections. Based on FA/ICGA examinations, we divided the patients into two categories: low vessel tortuosity (VT) (8.40), correlating VT with the MNV area, leakage area, speckled fluorescence (SF) quadrants and MNV area/leakage area ratio.Results: Mean baseline BCVA was 0.50 ± 0.61 LogMAR, improved to 0.31 ± 0.29 LogMAR after 1 year (p < 0.01), with a mean number of 7 ± 2 anti-VEGF injections. The patients revealed type-1 MNV in 36 eyes (55%), mixed type 1 and 2 MNV in 18 eyes (27%), and type-2 MNV in 12 eyes (18%). MNV eyes in high-VT MNV featured poorer BCVA, CMT, and OCTA parameters, higher SF quadrants, and less exudation, compared with low-VT MNV (p < 0.01). Moreover, 30% of high-VT MNV eyes developed outer retinal atrophy.Conclusions: Low VT MNV turned out to be more exudative at the baseline but less damaging to the outer retinal structures, whereas high VT MNV proved to be less exudative but more prone to lead to atrophic changes and visual function deterioration. VT may be usefully applied to artificial intelligence-based models designed to characterize MNV secondary to AMD.

Retinal arterial macroaneurysm (RAM) can be defined as an acquired round or fusiform dilation of a retinal artery. RAMs frequently remain stable but, in some cases, can complicate with macular exudation or hemorrhage, resulting in symptomatic disease. While a watch-and-wait approach is the standard option in asymptomatic RAMs, there is no universal agreement regarding treatment of symptomatic cases and randomized clinical trials are warranted. Anti-VEGF intravitreal injections can reduce exudation, albeit multiple treatments may be necessary. Hence, laser treatment may be a better choice to provide a durable control of symptoms while anti-VEGF therapy should be preferred for lesions adjacent to the fovea. Indirect laser is recommended because there is a decreased danger of RAM rupture and hemorrhage. Furthermore, subthreshold laser seems to be comparable to conventional laser in terms of efficacy outcomes.

Background: In this study, we aimed to discriminate high reflectivity and low reflectivity macular neovascularization (MNV) lesions secondary to age-related macular degeneration (AMD)and to assess the influence of blood flow features on the amount of MNV detected by optical coherence tomography angiography (OCTA).Methods: The study was designed as observational, cross-sectional. Type 1 and type 2 MNV lesions were included. All the patients underwent fluorescein angiography (FA), indocyanine green angiography (ICGA) and OCTA. MNV size was calculated on early FA for type 2 MNV and on both early and late phases of ICGA for type 1 lesions. From OCTA, we calculated both MNV size and MNV reflectivity. We assessed the agreement between FA/ICGA and OCTA MNV sizes. Moreover, we studied the relationship between MNV reflectivity properties and MNV OCTA detection.Results: Fifty eyes (50 patients) were included. MNV was identified as follows: 35 /70%) type 1 and 15 (30%) type 2. We found a good agreement between early ICGA size and OCTA size for type 1 MNV (2.10 ± 1.91 mm2 vs 2.09 ± 1.87 mm2; p > 0.05), whereas MNV lesions turned out to be remarkably bigger on late ICGA phase (3.41 ± 2.87 mm2; p < 0.01). Interestingly, OCTA well-matched with FA in terms of MNV size for type 2 lesions (2.36 ± 2.15 mm2 vs 2.37 ± 2.25 mm2). MNV reflectivity was higher in type 2 MNV and it was strongly associated with the OCTA ability to reconstruct the neovascular network.Conclusion: Our study quantitatively showed that MNV filling pattern and MNV blood flow reflectivity features influence the OCTA detection of the MNV in its entirety.

Central serous chorioretinopathy (CSC) is a controversial disease both in terms of clinical classification and choice of therapeutic strategy. Choroidal layers, retinal pigment epithelium (RPE), photoreceptors, and retina are involved to varying degrees. Beyond well-known symptoms raising the clinical suspect of CSC and slit-lamp fundus examination, multimodal imaging plays a key role in assessing the extent of chorioretinal structural involvement. Subretinal fluid (SRF) originating from the choroid leaks through one or multiple RPE defects and spreads into the subretinal space. Spontaneous fluid reabsorption is quite common, but in some eyes, resolution can be obtained only after treatment. Multiple therapeutic strategies are available, and extensive research identified the most effective procedures. Imaging has carved a significant role in guiding the choice of the most appropriate strategy for each single CSC eye. Multiple biomarkers have been identified, and all of them represent a diagnostic and prognostic reference point. This review aims to provide an updated and comprehensive analysis of the current scientific knowledge about the role of imaging in planning the treatment in eyes affected by CSC.

Currently, no general consensus exists regarding the management of central serous chorioretinopathy (CSC). Laser treatments include three different therapeutic approaches: conventional laser, subthreshold laser and photodynamic therapy. Conventional focal laser, addressed to seal the leaking points, as evidenced on fluorescein angiography, was largely used in the past, but now, it is almost completely abandoned, owing to the potential complications. Several studies confirmed the positive effects achieved by subthreshold laser treatment in CSC, even though its improper application in the PLACE trial has questioned the effectiveness.

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.

Summary: Background: Contemporary data for causes of vision impairment and blindness form an important basis of recommendations in public health policies. Refreshment of the Global Vision Database with recently published data sources permitted modelling of cause of vision loss data from 1990 to 2015, further disaggregation by cause, and forecasts to 2020. Methods: In this systematic review and meta-analysis, we analysed published and unpublished population-based data for the causes of vision impairment and blindness from 1980 to 2014. We identified population-based studies published before July 8, 2014, by searching online databases with no language restrictions (MEDLINE from Jan 1, 1946, and Embase from Jan 1, 1974, and the WHO Library Database). We fitted a series of regression models to estimate the proportion of moderate or severe vision impairment (defined as presenting visual acuity of 14% of blindness) as causes in the high-income subregions. Blindness and vision impairment at all ages in 2015 due to diabetic retinopathy (odds ratio 2·52 [1·48–3·73]) and cataract (1·21 [1·17–1·25]) were more common among women than among men, whereas blindness and vision impairment due to glaucoma (0·71 [0·57–0·86]) and corneal opacity (0·54 [0·43–0·66]) were more common among men than among women, with no sex difference related to age-related macular degeneration (0·91 [0·70–1·14]). Interpretation: The number of people affected by the common causes of vision loss has increased substantially as the population increases and ages. Preventable vision loss due to cataract (reversible with surgery) and refractive error (reversible with spectacle correction) continue to cause most cases of blindness and moderate or severe vision impairment in adults aged 50 years and older. A large scale-up of eye care provision to cope with the increasing numbers is needed to address avoidable vision loss. Funding: Brien Holden Vision Institute.

Background: Global and regional prevalence estimates for blindness and vision impairment are important for the development of public health policies. We aimed to provide global estimates, trends, and projections of global blindness and vision impairment. Methods: We did a systematic review and meta-analysis of population-based datasets relevant to global vision impairment and blindness that were published between 1980 and 2015. We fitted hierarchical models to estimate the prevalence (by age, country, and sex), in 2015, of mild visual impairment (presenting visual acuity worse than 6/12 to 6/18 inclusive), moderate to severe visual impairment (presenting visual acuity worse than 6/18 to 3/60 inclusive), blindness (presenting visual acuity worse than 3/60), and functional presbyopia (defined as presenting near vision worse than N6 or N8 at 40 cm when best-corrected distance visual acuity was better than 6/12). Findings: Globally, of the 7·33 billion people alive in 2015, an estimated 36·0 million (80% uncertainty interval [UI] 12·9–65·4) were blind (crude prevalence 0·48%; 80% UI 0·17–0·87; 56% female), 216·6 million (80% UI 98·5–359·1) people had moderate to severe visual impairment (2·95%, 80% UI 1·34–4·89; 55% female), and 188·5 million (80% UI 64·5–350·2) had mild visual impairment (2·57%, 80% UI 0·88–4·77; 54% female). Functional presbyopia affected an estimated 1094·7 million (80% UI 581·1–1686·5) people aged 35 years and older, with 666·7 million (80% UI 364·9–997·6) being aged 50 years or older. The estimated number of blind people increased by 17·6%, from 30·6 million (80% UI 9·9–57·3) in 1990 to 36·0 million (80% UI 12·9–65·4) in 2015. This change was attributable to three factors, namely an increase because of population growth (38·4%), population ageing after accounting for population growth (34·6%), and reduction in age-specific prevalence (−36·7%). The number of people with moderate and severe visual impairment also increased, from 159·9 million (80% UI 68·3–270·0) in 1990 to 216·6 million (80% UI 98·5–359·1) in 2015. Interpretation: There is an ongoing reduction in the age-standardised prevalence of blindness and visual impairment, yet the growth and ageing of the world's population is causing a substantial increase in number of people affected. These observations, plus a very large contribution from uncorrected presbyopia, highlight the need to scale up vision impairment alleviation efforts at all levels. Funding: Brien Holden Vision Institute.

Background: To identify different choroidal patterns in Stargardt disease (STGD) and to assess their clinical correlates. Methods: 100 STGD eyes (29 males; mean age 42.6 ± 16.5 years) and 100 control eyes (29 males; mean age 43.2 ± 8.5 years) were included. Optical coherence tomography (OCT) and OCT angiography (OCTA) images were obtained. Four different choroidal patterns, quantitative OCT and OCTA parameters were assessed and statistically analyzed. The main outcome was the correlation between each choroidal pattern and anatomical and functional retinal status. Furthermore, we assessed structural and best corrected visual acuity (BCVA) changes of each STGD subgroup after one-year. Results: Mean BCVA was 0.63 ± 0.44 LogMAR for STGD patients and 0.0 ± 0.0 LogMAR for controls (p < 0.01). All quantitative parameters appeared deteriorated in STGD compared to controls (p < 0.01). Choroidal patterns were distributed as follows: Pattern 1 (normal appearing choroid) (15%), Pattern 2 (reduced Sattler or Haller layer) (29%), Pattern 3 (reduced Sattler and Haller layers) (26%), Pattern 4 (Pattern 3 + choroidal caverns) (30%). More advanced patterns significantly correlated with a more severe loss of retinal structural integrity. Furthermore, only Pattern 3 and Pattern 4 showed remarkable signs of progression after one year. Conclusions: Choroidal patterns were related with retinal structural status and BCVA loss, and with different disease progression.

Background: Retinitis Pigmentosa (RP) represents a retinal dystrophy with an extremely complex pathogenesis further worsened by the impairment of the retinal vascular supply. The main goal of this study was to identify different vascular patterns in RP, by means of optical coherence tomography angiography (OCTA). Methods: A total of 32 RP patients (16 males, 50%; mean age 45.93 ± 11.4) and 32 healthy age-matched controls (16 males, 50%; age 42.8 ± 11.2). High resolution OCT and OCTA images were obtained from all participants. Several quantitative parameters were extracted both from structural OCT and OCTA images. A post-hoc analysis assessed the relationship between the quantitative OCTA parameters adopted and the following measures: best corrected visual acuity (BCVA), central macular thickness (CMT) and retinal nerve fiber layer (RNFL). Results: Mean LogMAR BCVA was 0.24 ± 0.32 for RP patients and 0.0 ± 0.0 for controls (p < 0.01). CMT, choroidal thickness and RNFL were statistically different between RP and controls (p < 0.01). OCTA parameters showed strong alterations of the retinal vascular network in RP (all p < 0.01). Several statistically significant correlations were also found. Furthermore, a vessel tortuosity cut-off of 4.80 and a vessel rarefaction cut-off of 0.62 enabled the RP cohort to be divided into two significantly different sub-groups in terms of BCVA, RNFL and CMT. Conclusions: Quantitative OCTA parameters help identify vascular abnormalities in RP, separating two different vascular patterns.