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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

Purpose: To assess the tomographic features of myopic choroidal neovascularization by spectral-domain optical coherence tomography. Methods: We consecutively reviewed the charts of patients with pathologic myopia, recent visual acuity deterioration and active macular neovascularization. Specific tomographic changes were studied in 25 eyes by two authors independently. Results: The mean age of patients eligible for the study was 63.4 (±18.2) years. Main tomographic outcomes were the hyperreflectivity of the lesion in 88% of cases (95% CI 0.74-1.02), absence of the external limiting membrane in 88% (95% CI 0.84-1.02), and retinal thickening in 83% (95% CI 0.67-0.99). The internal plexiform layer remained discernible in 83% (95% CI 0.67-0.99) of cases, the inner nuclear layer in 62% (95% CI 0.37-0.80), the external plexiform layer in 48% (95% CI 0.27-0.69). Retinal edema was noted in 48% (95% CI 0.26-0.70) of patients. Conclusions: Myopic choroidal neovascularization appears predominantly hyperreflective, causes thickening of the corresponding retina and mainly involves the external retinal segments. Retinal fluid is infrequent.

Myopic choroidal neovascularization (mCNV) has certain characteristics and features that distinguish it from choroidal neovascularization secondary to age-related macular degeneration. There may be angiographic diagnostic difficulties even when using the scanning laser ophthalmoscope, which gives more contrast and better definition than traditional angiography. The aim of the study is to compare the sensitivity of fluorescein angiography (FA) alone or combined with Spectral Domain Optical Coherence Tomography (SD-OCT) for assessing the incidence of mCNV.In this retrospective study, two authors reviewed the charts and images of patients with recent (30 days) vision deterioration, pathologic myopia, axial length26 mm, documentation or suspicion of mCNV or macular exudative pathologies at FA and OCT. They only examined the images at first presentation obtained by the multi-modal imaging system that combines Infrared reflectance, FA, and SD-OCT, (Spectralis, Heidelberg Engineering, Germany). The images selected were then evaluated by three other investigators in blinded, independent conditions, in order to make their diagnosis, which was noted or rated as doubtful if it could not be decided on the basis of FA alone. SD-OCT images were then shown and compared to IR and FA by each of the three investigators individually to formulate a conclusive diagnosis.A total of 71 eyes of 69 patients were suitable for the study, mean age 65.97±14.57 years, spherical equivalent refraction -8.82 ± 2.51 diopters. Concordance between the three examiners' interpretations of FA features and FA-guided SD-OCT was 50/71 (70.4 %) and 67/71 (94 %) respectively. Total agreement on diagnosis between the three examiners was achieved in 55 % of cases for FA (κ = 0.53, p0.001), and 94 % for FA-guided SD-OCT (k = -0.01, p = 0.5). The final diagnosis with FA and FA-guided SD-OCT differed in 29 cases (40 %; 95 % C.I. 29-42 %), whereas 12 (17 %) mCNV were overlooked at FA, and in 11 (15 %) cases none of the examiners reached a diagnosis based on FA alone.On the basis of FA alone, active mCNV can be misdiagnosed. The use of SD-OCT combined with FA should therefore be strongly considered.

The purpose of the study was to ascertain the prevalence of retinal angiomatous proliferation (RAP) by means of dynamic indocyanine green angiography (d-ICGA) in patients with newly diagnosed fibrovascular pigment epithelium detachment (type 1) or late leakage of undetermined source (type 2) occult choroidal neovascularization (CNV) on fluorescein angiography.We carried out a review of digital fluorescein and ICG angiograms obtained by confocal scanning laser ophthalmoscope (HRA; Heidelberg Engineering GmbH, Dossenheim, Germany) in 253 consecutive patients (270 eyes) with a clinical diagnosis of type 1 or type 2 occult CNV on fluorescein angiography (1998 through 2003).Sixty eyes had type 1 and 210 eyes type 2 occult CNV on fluorescein angiography. Overall, 57 cases of RAP were identified in 54 eyes (20%) with d-ICGA. RAP was present in 6 out of 60 eyes with type 1 (10%) and in 51 out of 210 eyes with type 2 occult CNV (24%). Mean distance of the lesion from the fovea was 682 +/- 304 microm (mean +/- SD).d-ICGA is invaluable for early diagnosis of RAP in exudative age-related macular degeneration (ARMD). In our series, up to one fourth of type 2 occult CNV were in fact RAP.

Paolo Milani, Amedeo Massacesi, Stefano Ciaccia, Marco Setaccioli, Stefania Moschini, Fulvio BergaminiDipartimento di Oculistica, Istituto Auxologico Italiano, Milano, ItalyBackground: The aim of this study was to evaluate the efficacy of intravitreal bevacizumab when administered on an as-needed basis for the treatment of myopic choroidal neovascularization (CNV), and to assess visual changes upon treatment.Methods: This study was designed as a retrospective, interventional case series, for which the inclusion criteria were pathologic myopia, and documentation of untreated active macular CNV on fluorescein angiography and optical coherence tomography. Monthly changes in best-corrected visual acuity (BCVA), visual gain after each treatment, and correlation with refraction, age, location, and dimension of CNV were considered. The data were analyzed using the one-tailed, paired Wilcoxon test.Results: Nineteen naive eyes were found suitable for the study. The mean number of treatments was 3.32 ± 2.36 (confidence interval 2.25–4.37) during a mean follow-up period of 18.95 ± 8.3 months. At baseline, mean BCVA was 0.58 ± 0.37 logarithm of the minimum angle of resolution (logMAR) units. At 12 months, mean BCVA was 0.39 ± 0.35 logMAR and at 24 months was 0.39 ± 0.40. Mean improvement in BCVA from baseline was +0.17 ± 0.25 logMAR (P < 0.05) at month 12, +0.14 ± 0.25 logMAR (P = 0.1) at month 18, and +0.09 ± 0.32 logMAR (P = 0.5) at month 24. Improvement on pretreatment BCVA was significant (+0.16 logMAR, P < 0.01) after the first injection, but not after the second (−0.01 logMAR, P = 0.5) or third (+0.02 logMAR, P = 0.5) injections. There was a statistically significant correlation between age and number of treatments, and between improvement in BCVA of foveal versus extrafoveal location of CNV.Conclusion: The use of intravitreal bevacizumab "as needed" is an effective treatment for myopic CNV, but visual gain is statistically significant only after the first injection and decreases in the second year.Keywords: choroidal neovascularization, macular degeneration, pathologic myopia, bevacizumab, optical coherence tomography

Aim: To assess fundus autofluorescence (AF) for differential diagnosis of macular pseudoholes (MPH) and lamellar macular holes (LMH) evaluated by optical coherence tomography (OCT) as the “gold standard”. Methods: The files on 50 eyes of 46 consecutive patients diagnosed by OCT as having a foveal defect with residual retinal tissue at the bottom were reviewed. Retinal thickness was measured at the foveal centre and 750 μm temporally and nasally to differentiate further MPH and LMH. The corresponding corrected AF images were then evaluated. Eyes with either macular pucker or stage 1a impending macular hole served as controls. Results: OCT measurements allowed the classification of two different profiles: 28 eyes classified with MPH had macular centres and perifoveal retinas that were significantly thicker than the 22 eyes classified with LMH. The corrected value of the foveal AF intensity was not significantly different between the two groups. In addition, the AF did not correlate with the thickness of the retinal tissue at the base of either MPH or LMH eyes. None of the control eyes showed foveal AF. Conclusions: The findings suggest that OCT data must be interpreted with caution when differentiating between MPH and LMH. In this series, the two groups showed similar foveal AF. AF imaging may add useful information to the differential diagnosis of MPH from LMH: the presence of foveal AF is consistent with a loss of foveal tissue and therefore a diagnosis of LMH.

Background: The objective was to describe the remodeling of the vascular channels in stage II retinal angiomatous proliferation (RAP) treated by intravitreal injections of triamcinolone acetonide (TA)and subsequent photodynamic therapy(PDT). Methods: Stage II RAP secondary to age-related macular degeneration was documented by dynamic digital fluorescein and indocyanine green angiography in 3 consecutive patients (3 eyes). All eyes were treated with intravitreal injection of TA (4 mg, 0.1 ml) followed by PDT 5–10 days later. Results:Indocyanine green angiography(ICGA) revealed a complete remodeling of the vascular structure of the three RAPs after treatment. The feeding retinal artery, which shunted a major part of the blood flow from the original arteriole toward the intraretinal neovascular complex before treatment, regained a normal appearance after treatment. With RAP closure, the blood flow was again directed through the original retinal arteriole, and the connection to the RAP was no longer visible. Conclusions: Stage II RAPs are difficult lesions to treat. A real remodeling of the vascular lesion is achieved with the combined use of intravitreal TA and PDT. This finding corroborates the need for randomized clinical trials currently under way to evaluate this combinationtreatment in wet, age-related macular degeneration.

A corneal button excised from a 2-month-old infant with congenital posterior polymorphous dystrophy of the cornea, a rare disease affecting Descemet's membrane and endothelium, was examined by electron microscopy. We observed irregularly arranged, sometimes multilayered cells with marked epithelial features, lining the posterior surface of the cornea in place of the endothelium, and Descemet's membrane with focal alterations sometimes involving all of its layers. We interpreted these abnormal cells as epithelial-like cells. As these findings were in a very young patient, which is unusual, we concluded that the onset of the disease may take place in the early period of intrauterine life, corresponding to the beginning of Descemet's membrane production.