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Purpose:To propose an algorithm of the major and minor diagnostic criteria for macular myopic choroidal neovascularization (mCNV). Methods:This single-center, retrospective, cross-sectional study was based in Istituto Auxologico Italiano, Milan, Italy. Two authors evaluated the clinical and imaging parameters of eyes with high myopia (spherical equivalent of -6D or less) and suspected to have naïve, recurrent, or inactive mCNV. Recordings of the eyes that met the inclusion criteria were then independently evaluated by two other senior retinal specialists. Fluorescein angiography (FA), spectral domain optical coherence tomography (SD-OCT), and OCT angiography were used for multimodal imaging. Results:One-hundred and twenty-two eyes (n = 107; 39 men, 68 women) were included in the study. The mean patient age was 66 years (range, 22-89 years). There were 83 and 39 eyes in the active mCNV and control groups, respectively. The best diagnostic algorithm had positive- and negative-predictive values of 89% and 85%, respectively, and was based on four criteria: leakage/staining on FA, retinal thickening, fuzzy area on SD-OCT, and recent metamorphopsia. When excluding FA-derived findings, retinal pigment epithelium (RPE) features played a diagnostic role in 33 eyes (27%). Twenty-seven eyes with active mCNV (32%) did not have the fuzzy area. Taken singularly, no clinical or imaging parameter had both sensitivity and specificity greater than 78%. Matching of 2 or 3 biomarkers did not yield a sensitivity or specificity greater than 79%. Sensitivities and specificities ≥ 90% were found in ten criteria combinations that included four to five biomarkers. The most frequent were metamorphopsia, fuzzy area, retinal thickening, and leakage. Less frequently, they included hemorrhage, staining, and RPE features such as elevation, flattening, and focal interruption. For all the parameters, the agreement between the investigators was good (Cohen k ≥ 0.66), being the lowest when detecting the ELM interruption within the lesion. Conclusions:A combination of at least four clinical and biological markers yielded the highest positive- and negative-predictive values. More ("major") and less ("minor") frequent diagnostic criteria are proposed.

Purpose To describe a case of congenital retinal macrovessel complicated by cystoid macular edema associated with contralateral myelinated retinal nerve fibers and retinal vascular abnormalities studied with optical coherence tomography angiography (OCTA). Methods Case report. Results A healthy 25-year-old woman with decreased vision in her right eye was found to have a congenital retinal venous macrovessel in the macula associated with cystoid edema. In the contralateral amblyopic eye, the examination revealed a tuft of myelinated retinal nerve fibers along the superotemporal vascular arcade associated with superficial vascular abnormalities. A complete multi-imaging examination was obtained, including fundus color photography, fluorescein angiography, indocyanine green angiography, optical coherence tomography (OCT), and optical coherence tomography angiography. At 1-week follow-up, the optical coherence tomography displayed spontaneous resolution of the edema that remained stable at consecutive 1-month follow-up. Conclusion Congenital retinal macrovessels can be associated with other ocular developmental anomalies. Vascular complications can occur, leading to macular edema and retinal ischemia. Optical coherence tomography angiography can be useful for the diagnosis and follow-up of this condition.

Purpose To describe the optical coherence tomography (OCT) angiography features of subretinal fibrosis in eyes with myopic choroidal neovascularization after natural evolution or secondary to intravitreal anti-vascular endothelial growth factor therapy. Methods Retrospective observational case series. All eyes underwent a multimodal imaging examination including fluorescein angiography, spectral domain OCT, OCT angiography, and en face OCT. Results Twenty-five eyes of 25 patients with mean age of 56.4 ± 14.9 were included in the study. Subretinal fibrosis was diagnosed at mean 30 (range 6-116) months before inclusion. Within the subretinal fibrosis, an abnormal vascular network was observed in 20/25 (80%) eyes, located typically in the outer retina (18/20, 90%) or the choriocapillaris (14/20, 70%) segmentation. The most prevalent patterns were "round tangle" and "tapered tangle." On en face OCT, the subretinal fibrosis was evidenced in 24/25 (96%) eyes, most prevalently in the outer retina (21/25, 84%) and in the choriocapillaris (18/25, 72%), where main feature was white-hyperreflective (20/21, 95%) and dark-hyporeflective (17/18, 94%) appearance, respectively. The presence of subretinal fibrosis on en face OCT was positively correlated with the presence of abnormal vascular network on OCT angiography in 61% of the cases (P = 0.005). Conclusion Subretinal fibrosis secondary to myopic choroidal neovascularization frequently contains blood flow within a persistent abnormal vascular network as assessed by OCT angiography.

Sara Bochicchio,1 Paolo Milani,1 Lara Enrica Urbini,1 Ennio Bulone,1 Luciana Carmassi,1 Elena Fratantonio,1 Giacomo Castegna,1 Lorenza Scotti,2 Antonella Zambon,2 Fulvio Bergamini1 1Ophthalmology Department, Istituto Auxologico Italiano, Milan, Italy; 2Statistics and Quantitative Methods Department, University of Milano-Bicocca, Milan, ItalyCorrespondence: Paolo MilaniIstituto Auxologico Italiano, Via Mercalli 30, Milan, ItalyTel +39 2 3385840232Fax +39 2 20422262Email dottpaolomilani@hotmail.comPurpose: By using optical coherence tomography angiography (OCTA), to evaluate diurnal changes of the following parameters: vessel density in the peripapillary area (PP-VD) and in the optic nerve head (ONH-VD); thickness of retinal nerve fibre layer (RNFL) and ganglion cell complex (GCC).Methods: All prospectively enrolled participants were imaged on the same day at 8 am and 7 pm by means of the XR Avanti device with AngioVue and AngioAnalytics software (Optovue Inc., Fremont, CA, USA). Only eyes with correct automatic segmentation and good-quality images (scan quality > 7/10) were included.Results: Forty-six eyes from 28 patients with glaucoma, 53 from 31 patients with ocular hypertension, and 62 from 38 controls were assessed. The mean measurements of all parameters investigated were significantly different in the morning and in the evening values in all three groups, with lower values in glaucomatous eyes (p0.1).Conclusion: Vessel density, GCC and RNFL were stable during daytime thus corroborating the clinical relevance of OCTA regardless the time of acquisition.Keywords: glaucoma, optical coherence tomography angiography, vessel density, daily fluctuations, retinal fiber layer

Ultrasound cyclo plasty (UCP) is a recently developed surgical technique for glaucoma allowing a selective and controlled coagulation of the ciliary body. We herein investigated the long-term efficacy and safety of UCP for the treatment of glaucoma. This prospective study included patients with primary and secondary glaucoma. All surgeries were performed using the EyeOP1 device (Eye Tech Care, Rillieux-la-Pape, France). Sixty-six patients were included, and 60 completed regularly the 2-year follow-up. Preoperative IOP was 28.5 ± 9.6 mmHg and significantly decreased to 17.0 ± 5.4 at 2 years (p p

Purpose To assess quantitatively the choriocapillaris (CC) perfusion area in the macular area of healthy eyes, eyes with primary open-angle glaucoma, and eyes with ocular hypertension using optical coherence tomography angiography (OCTA). Methods A consecutive series of healthy individuals and patients with glaucoma and ocular hypertension were recruited prospectively in this single-center, cross-sectional study based in Milan, Italy. OCTA was performed in the morning and evening, along with a complete ophthalmologic examination. Macular superficial capillary plexus vessel density (SCP-VD) and the thicknesses of the retina and ganglion cell complex (GCC), as well as their fluctuations, were investigated. Results Thirty-nine eyes from 24 individuals with glaucoma (mean age = 58.79 ± 6 years), 43 eyes from 27 individuals with ocular hypertension (59.19 ± 6 years), and 54 eyes from 35 controls (58.27 ± 6 years) were enrolled. The mean CC perfusion area values were not significantly different among the three groups in the morning or evening (P ≥ 0.47). In contrast, SCP-VD, retinal thickness, and GCC thickness were statistically different among the groups (P ≤ 0.016), except for the foveal SCP-VD (P ≥ 0.19) and the evening foveal thickness (P = 0.57). Diurnal changes in the CC perfusion area, SCP-VD, retinal thickness, and GCC thickness were not statistically significant (P ≥ 0.16). Systemic hypertension, sex, age, axial length, and diurnal changes in intraocular pressure were not significantly associated with morning or evening measurements, or with diurnal fluctuations (P ≥ 0.07). Conclusions The macular CC flow perfusion area appears unaffected in eyes with primary open-angle glaucoma. No significant diurnal changes were observed in any of the parameters investigated.

Precis:Macular superficial capillary plexus (SCP) and thickness are reduced in eyes with glaucoma and ocular hypertension, but do not change significantly during the day. No relationships with age, intraocular pressure, systemic hypertension, or axial length were found.Purpose:The purpose of this study was to evaluate diurnal differences in retinal thickness and vessel density (VD) of the macular SCP and deep capillary plexus (DCP) using optical coherence tomography angiography among 3 groups: eyes with glaucoma, eyes with ocular hypertension, and healthy eyes.Methods:A consecutive series of individuals was recruited prospectively. Optical coherence tomography angiography was performed in the morning and in the evening.Results:Forty eyes from 23 individuals with glaucoma (58.35±6 y), 52 eyes from 32 individuals with ocular hypertension (58.84±7 y), and 73 eyes from 44 controls (57.84±6 y) were enrolled. Morning and evening measurements of all SCP-VD and retinal thickness parameters were statistically significantly different (P0.19). A positive linear correlation in diurnal changes was found between SCP-VD and DCP-VD in the fovea and in the parafovea (r=0.5567 and 0.5892, respectively) and between SCP-VD and retinal thickness in the fovea and in the parafovea (r=-0.2288 and 0.2418, respectively).Conclusions:Macular SCP-VD and thickness are reduced in eyes with glaucoma and ocular hypertension. Although diurnal changes in SCP-VD, DCP-VD and macular thickness were not significant among the groups, some linear correlations in increasing or decreasing values of the investigated parameters were found.

Purpose: To evaluate functional prognostic factors and neuroretinal changes after anti-vascular endothelial growth factor (VEGF) treatment in patients with naïve, recent myopic neovascularization (mCNV), as assessed by spectral-domain optical coherence tomography (SD-OCT). Methods: Specific changes in tomographic features between baseline and final follow-up were retrospectively evaluated by two examiners independently. Imaging was obtained by a multi-modal imaging system which combines fluorescein angiography and SD-OCT. Results: Twenty-two eyes (male, six; female, 16; mean age, 65 ± 14 years) were considered. Mean follow-up was 21.5 ± 14 months. Best-corrected visual acuity (BCVA) improved from 0.38 ± 0.26 to 0.16 ± 0.20 logMAR (p

Purpose: The aim of this study was to evaluate the safety and efficacy of ultrasound cyclo-plasty (UCP) for reducing intraocular pressure (IOP) in patients with glaucoma. Methods: This is a multicentre prospective study conducted in 3 Italian glaucoma centres. UCP was performed by EyeOP1, which delivers ultrasound beams using 6 piezoelectric transducers activated for 4/6 s (first generation) or 8 s (second generation). Primary outcomes were the mean IOP reduction and the rates of success after 1 year. Secondary outcomes were the mean IOP reduction at each follow-up, and the reduction of the number of hypotensive medications. Results: In total, 49 eyes from 47 patients were treated. One year postoperatively, the mean IOP had decreased from 27.7 ± 9.2 to 19.8 ± 6.9 mm Hg (p < 0.001), and the mean number of hypotensive drops and tablets had decreased from 3.2 and 0.5 to 2.3 and 0.2, respectively (p < 0.05). Postoperative IOP reduction was significantly related to preoperative IOP (r2 = 0.5034; p < 0.0001). Second-generation probes determined a significantly higher IOP reduction (p < 0.05). Qualified success was achieved in 25 eyes (51.1%) and complete success in 21 (42.9%), while failure was recorded in 12 (24.5%). Conclusions: UCP is safe and effective for reducing IOP. The procedure determines a greater IOP reduction in patients with higher preoperative IOP. Second-generation probes improve outcomes without detrimental effects on safety.

Paolo Milani,1 Amedeo Massacesi,1 Stefania Moschini,1 Marco Setaccioli,1 Ennio Bulone,1 Gemma Tremolada,1 Stefano Ciaccia,1 Elena Mantovani,1 Daniela Morale,2 Fulvio Bergamini1 1Ophthalmology Department, Istituto Auxologico, 2Institute of Mathematics, Universita’ degli Studi di Milano, Milan, Italy Purpose: To investigate myopic choroidal neovascularization (mCNV) by fluorescein angio­graphy (FA), spectral-domain optical coherence tomography (SD-OCT), near-infrared (NIR) reflectance, and autofluorescence (AF). Methods: This retrospective study included 65 eyes of 62 Caucasian patients with a mean age of 66.72 years (95% confidence interval [CI] 63–70 years) and a mean refraction of -9.72 diopters (95% CI -8.74 to -10.70 diopters). Results: Most of the mCNV cases were foveal-juxtafoveal (60/65, 92.3%), with thickening of the corresponding retina (62/65, 95.3%) and leakage on FA (44/65, 67.6%). No retinal fluid was detectable in 32 (49.2%) eyes and there was no hemorrhage in 25 (38.4%) eyes. Papillary chorio­retinal atrophy was evident in 58 (89.2%), a shadowing effect in 48 (73.8%), and an epiretinal membrane in 38 (58.4%) eyes. If an area of macular chorioretinal atrophy was present, mCNV frequently developed adjacent to it and was hyperfluorescent rather than with leakage (P

To evaluate the plasma concentration of the soluble form of the urokinase-type plasminogen activator receptor ((s)uPAR), an established biomarker of chronic inflammation, in patients affected by neovascular age-related macular degeneration. Forty consecutive patients affected by age-related macular degeneration and 52 subjects with no history of the disease were included in this case–control study. The two groups of individuals considered for the study were matched for age, sex, and class of medications taken. Plasma concentration of suPAR was measured using a specific ELISA assay (suPARnostic, Birkeroed, Denmark). The case and control groups were similar for age, gender distribution, weight, height, and systolic and diastolic blood pressure, as well as for dyslipidemia and high blood pressure medication (P > 0.28). The plasma concentrations of suPAR were significantly increased in patients with neovascular age-related macular degeneration when compared to controls (6.19 ± 2.2 ng/ml, vs 5.21 ± 1.5, respectively, mean ± SD P = 0.01). Patients with neovascular age-related macular degeneration display increased plasma levels of suPAR, suggesting that chronic inflammation may be involved in the pathogenesis of the disease.

To investigate foveal avascular zone area, macular vascular density, choroidal thickness, and outer retina and choriocapillaris flow in myopic eyes by OCT angiography. Automated macular maps and flow calculations were retrospectively evaluated in 42 myopic and in 40 control eyes. Myopic eyes presented lower whole superficial vessel density (46.4 ± 4.9 vs. 51.6 ± 3.6%, P