paolo milani

@auxologico.it

Ophthalmology Department
Istitituto Auxologico Italiano

RESEARCH INTERESTS

retina, macula

33

Scopus Publications

Scopus Publications

  • A Global and Sector-Based Comparison of OCT Angiography and Visual Field Defects in Glaucoma
    Alan W. Kong, Marcus L. Turner, Murtaza Saifee, Mohit Jethi, Marta Mora, and Yvonne Ou

    Hindawi Limited
    Purpose. To evaluate the correlation of optical coherence tomography angiography (OCTA) and spectral-domain optical coherence tomography (SD-OCT) with visual field for global and sector-based indices among glaucoma and glaucoma-suspected eyes. Patients and Methods. This is a retrospective study, and in total, 48 glaucoma eyes and 31 glaucoma suspect eyes were included. The correlation between visual field parameters and radial peripapillary capillary (RPC) vessel density via OCTA was compared to the correlation with retinal nerve fiber layer (RNFL) thickness via SD-OCT. The RPC vessel density and RNFL thickness were divided into eight sectors, which included the temporal upper, temporal lower, superotemporal, inferotemporal, superonasal, inferonasal, nasal upper, and nasal lower sectors. Pearson correlations with 95% confidence intervals were calculated with resampling, and correlations were compared with a Fisher Z transformation. Results. Both RPC vessel density (R = 0.63, 95% CI [0.24, 0.86]) and RNFL thickness (R = 0.49, 95% CI [0.23, 0.69]) were correlated with the mean deviation when comparing global indices of glaucoma patients. In glaucoma suspects, the correlations between the mean deviation and RPC vessel density (R = 0.21, 95% CI [−0.05, 0.49]) and RNFL thickness (R = 0.01, 95% CI [−0.35, 0.39]) were not significant. Glaucoma eyes had the highest correlation between the mean sensitivity and RPC vessel density and RNFL thickness for the superotemporal, superonasal, temporal upper, and inferotemporal sectors. Conclusion. Across a diverse population and heterogeneous glaucoma types, RPC vessel density measurements correlate with global and sector-wise visual field indices similar to RNFL thickness.

  • Algorithm of the major and minor diagnostic criteria for active myopic choroidal neovascularization
    Paolo Milani, Marco Mazzola, Mario Cigada, Amedeo Massacesi, Marco Setaccioli, Stefania Moschini, Stefano Ciaccia, Fabrizio Scotti, Elena Mantovani, Davide Soranna,et al.

    Springer Science and Business Media LLC

  • Suprachoroidal haemhorrage and vortex vein varix: A potential association
    Paolo Milani, Marco Mazzola, and Fulvio Bergamini

    SAGE Publications
    Purpose: To report on the association between a vortex vein varix and suprachoroidal hemorrhage. Case description: A healthy 60 years-old man with high myopia (–10 diopters) was seen because of sudden paracentral metamorphopsias after emesis. Multimodal imaging included Spectral-Domain Optical Coherence Tomography (SD-OCT), ultrasonography and retinal angiography with fluorescein and indocyanine green. His vision was 20/20 but clinical assessment and imaging procedures evaluations showed a suprachoroidal hemorrhage in the temporal part of the para-macular area. The lesion corresponded to a mild hypo-fluorescence area on fluorescein angiography and to a massive detachment of the inner part of the choroid from the suprachoroidal space on SD-OCT. Indocyanine green angiography disclosed engorgement of a big choroidal vessel in the area of the lesion. An adjacent vortex vein varix was found on SD-OCT. A few weeks later the suprachoroidal hemorrhage resolved spontaneously, whereas the vortex vein varix persisted. Conclusion: We speculate that vortex vein varixes might represent a risk factor for the occurrence of suprachoroidal hemorrhage in high myopia and that this association may be worth investigating. Summary statement: In a high myopia suprachoroidal hemorrhage might be secondary to vortex vein varixes.

  • OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FINDINGS IN A CASE OF CONGENITAL RETINAL MACROVESSEL WITH ANOMALOUS RETINAL ANASTOMOSIS ASSOCIATED WITH CONTRALATERAL MYELINATED NERVE FIBERS AND RETINAL VASCULAR ABNORMALITIES
    Chiara Preziosa, Paolo Milani, Paola Ciasca, Fulvio Bergamini, Giovanni Staurenghi, and Marco Pellegrini

    Ovid Technologies (Wolters Kluwer Health)
    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.

  • The macular choriocapillaris flow in glaucoma and within-day fluctuations: An optical coherence tomography angiography study
    Paolo Milani, Lara Enrica Urbini, Ennio Bulone, Ugo Nava, Deborah Visintin, Giorgia Cremonesi, Lorenza Scotti, and Fulvio Bergamini

    Association for Research in Vision and Ophthalmology (ARVO)
    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.

  • Comment on: Diagnostic algorithm utilising multimodal imaging including optical coherence tomography angiography for the detection of myopic choroidal neovascularization
    Paolo Milani, Fabrizio Scotti, and Fulvio Bergamini

    Springer Science and Business Media LLC
    Bagchi et al. [1] interestingly purposed a decision-making flow chart for cases clinically suspected of myopic choroidal neovascularization (mCNV) that may occasionally be misdiagnosed. In addition to an accurate clinical examination, diagnosis with complete multimodal imaging remains the best strategy because the sensitivity and specificity of spectral-domain optical coherence tomography (SD-OCT), optical coherence tomography angiography (OCTA), and fluorescein angiography (FA) alone is good but not infallible with a sensitivity ranging from 94 to 74% [1]. However, we believe that the flow chart warrants reconsideration for two main reasons. First, difficulty in determining the lesion activity clinically or on tomographic imaging. Some patients have reduced baseline visual acuity due to high myopia or concomitant diseases, such as amblyopia, cataract, and glaucoma. Therefore, these patients, especially those who are old, may be oblivious to further visual deterioration for months and may seek ophthalmologists’ care months after symptom onset when the mCNV is in the scar stage. Thus, non-invasive and fast SD-OCT to assess lesion characteristics becomes crucial, but in some eyes tomographic signs of activities, including the presence of hyperreflective material with intraretinal or subretinal fluid, intraretinal fuzzy area, and retinal pigment epithelium elevation, may be difficult to detect or dependent on the examiners’ interpretation and experience. Similarly, presence of ellipsoid zone and external limiting membrane interruption as signs of activity, as reported by some authors [2, 3], require additional validation and consensus since visual improvement and mCNV inactivity may occur after intravitreal treatment despite ellipsoid zone and external limiting membrane reconstitution within the lesion [4]. Occasionally, it is challenging to distinguish fibrosis from active mCNV on SDOCT. In such cases, OCTA may be potentially helpful, although there is a risk of false-negative diagnosis because of macular haemorrhage and chorioretinal atrophy. In fact, mCNV was identified on OCTA in 74.07% of cases by Bagchi et al. [1], concluding that the lesion shape (tight rather than a loose net) and presence of a black surrounding halo are the characteristic features of activity. In contrast, a low specificity of choroidal dark halo with no association with lesion activity was reported recently [5]. We therefore strongly believe that interpretation of mCNV features on OCTA is inter-observer dependent and that artifacts and acquisition modality can greatly affect diagnosis, eventually leading to poor quality imaging in almost 24.1% of cases [5]. Nevertheless, we reported that in 80% of fibrosis secondary to mCNV (inactive mCNV), the original neovascular network remains well discernable several months after treatment even if enclosed within the scar area [6]. This observation, in particular, seems inconsistent with the proposed algorithm. According to it, mCNV should be treated if considered negative on SD-OCT but positive on OCTA (as commonly seen with fibrosis or inactive mCNV) independently from its features on FA. Evidently, although SD-OCT is mostly sufficient for accurately diagnosing mCNV, we are convinced that FA should be strongly considered in mCNV cases with negative or doubtful SD-OCT outcomes, regardless of its invasiveness. In these cases, combined SD-OCT with OCTA, when available, may provide inaccurate diagnosis and lead to * Paolo Milani dottpaolomilani@hotmail.com

  • Diurnal measurements of macular thickness and vessel density on OCT angiography in healthy eyes and those with ocular hypertension and glaucoma
    Paolo Milani, Sara Bochicchio, Lara Enrica Urbini, Ennio Bulone, Stefania Callegarin, Luca Pisano, Lorenza Scotti, Antonella Zambon, and Fulvio Bergamini

    Ovid Technologies (Wolters Kluwer Health)
    Supplemental Digital Content is available in the text. 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 (P<0.04) among the 3 groups of eyes. None of the DCP-VD parameters were significantly different. Daily changes in SCP-VD, DCP-VD, and retinal thickness among the groups of eyes were not statistically significant. Systemic hypertension, age, axial length, and diurnal changes in intraocular pressure were not significantly associated with diurnal fluctuations of SCP-VD, DCP-VD, or retinal thickness (P>0.19). 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.

  • OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FEATURES OF SUBRETINAL FIBROSIS AFTER MYOPIC NEOVASCULARIZATION
    Paolo Milani, Marco Pellegrini, Amedeo Massaccesi, Fabrizio Scotti, Stefania Moschini, Marco Setaccioli, Roberta Secondi, and Fulvio Bergamini

    Ovid Technologies (Wolters Kluwer Health)
    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.

  • Increased soluble urokinase plasminogen activator receptor (suPAR) levels in neovascular age-related macular degeneration: a role for inflammation in the pathogenesis of the disease?
    Fabrizio Scotti, Paolo Milani, Marco Setaccioli, Silvia Maestroni, Nicolai Sidenius, Valentina De Lorenzi, Amedeo Massacesi, Fulvio Bergamini, and Gianpaolo Zerbini

    Springer Science and Business Media LLC
    PurposeTo 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.MethodsForty 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).ResultsThe 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).ConclusionsPatients 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.

  • Diurnal stability of peripapillary vessel density and nerve fiber layer thickness on optical coherence tomography angiography in healthy, ocular hypertension and glaucoma eyes
    Sara Bochicchio, Paolo Milani, Lara Enrica Urbini, Ennio Bulone, Luciana Carmassi, Elena Fratantonio, Giacomo Castegna, Lorenza Scotti, Antonella Zambon, and Fulvio Bergamini

    Informa UK Limited
    Purpose 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 (p<0.014). In control eyes, as well as in eyes of patients with ocular hypertension and glaucoma the daily changes were minimal and not statistically significant with means of +0.17%, −0.31% and −0.54% for ONH-VD (p=0.83) and means of +0.2%, +0.1% and +0.29% for PP-VD (p=0.83), respectively. Likewise, daily fluctuations in GCC and RNFL thickness were not significant in any of the three groups, with means of +0.16 µm, +0.66 µm and −0.15 µm for GCC (p=0.58) and means of +0.24 µm, +0.58 µm and −0.24 µm for ONH-RNFL (p=0.90), respectively. Systemic hypertension, age, axial length, daily changes in intraocular pressure or scan quality did not correlate with daily fluctuations of any of the parameters investigated (p>0.1). Conclusion Vessel density, GCC and RNFL were stable during daytime thus corroborating the clinical relevance of OCTA regardless the time of acquisition.

  • Vessel density, retinal thickness, and choriocapillaris vascular flow in myopic eyes on OCT angiography
    Paolo Milani, Giovanni Montesano, Luca Rossetti, Fulvio Bergamini, and Alfredo Pece

    Springer Science and Business Media LLC
    PurposeTo investigate foveal avascular zone area, macular vascular density, choroidal thickness, and outer retina and choriocapillaris flow in myopic eyes by OCT angiography.MethodsAutomated macular maps and flow calculations were retrospectively evaluated in 42 myopic and in 40 control eyes.ResultsMyopic eyes presented lower whole superficial vessel density (46.4 ± 4.9 vs. 51.6 ± 3.6%, P < 0.0001) and higher flow area in the outer retina (1.3 ± 0.2 vs. 1.1 ± 0.3 mm2, P = 0.0012). Between the myopic and non-myopic eyes, no significant differences could be detected in the choriocapillaris perfusion area (1.9 ± 0.07 vs. 1.9 ± 0.05 mm2, respectively; P = 0.55) and in the foveal avascular zone area (0.23 ± 0.1 vs. 0.26 ± 0.1 mm2, respectively; P = 0.12). The spherical correction positively correlated with superficial vessel density and negatively correlated with outer retina perfusion (P ≤ 0.0021). The superficial vessel density and the local retinal thickness positively correlated at all macular locations (P < 0.005), especially in the foveal region (P < 0.0001).ConclusionsEyes with high myopia present reduced superficial vascular density and increased outer retina flow. Superficial vascular density and retinal thickness appear to be significantly correlated.

  • Is ellipsoid zone integrity essential for visual recovery in myopic neovascularization after anti-VEGF therapy?
    Paolo Milani, Marco Pellegrini, Amedeo Massacesi, Stefania Moschini, Marco Setaccioli, Davide Soranna, Antonella Zambon, Ferdinando Bottoni, and Fulvio Bergamini

    Springer Science and Business Media LLC
    PurposeTo 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).MethodsSpecific 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.ResultsTwenty-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 < 0.001). The ellipsoid zone and the external limiting membrane (ELM) were disrupted in 21 (95.5%) and 15 (68.2%) eyes at baseline, and in 16 (72.7%) and nine (40.9%) eyes after therapy respectively. The ellipsoid zone and ELM were typically intact at lesion margins in 13 (59.1%) and 19 eyes (86.5%) respectively at baseline. The inner retina was intact in 20 eyes (91%). Six eyes (27.3%) exhibited complete regression without fibrosis. Absence of hemorrhage and integrity of lesion-adjacent ELM and of lesion-adjacent ellipsoid zone at baseline were factors for better final BCVA (p ≤ 0.05)ConclusionVision gain might occur despite ellipsoid zone or ELM restoration. Hemorrhage could be considered a negative prognostic factor, integrity of lesion-adjacent ELM and of lesion-adjacent ellipsoid zone as positive prognostic factors. Myopic CNV can also resolve completely without fibrosis.

  • Spontaneous Hemorrhage or Myopic Neovascularization on OCT Angiography
    Paolo Milani, Luisa Pierro, and Alfredo Pece

    Elsevier BV

  • Intravitreal aflibercept for myopic choroidal neovascularization
    Alfredo Pece and Paolo Milani

    Springer Science and Business Media LLC
    PurposeTo assess the use of aflibercept for the treatment of subfoveal myopic choroidal neovascularization (CNV).MethodsThirty-two patients (33 eyes) with myopic subfoveal CNV were consecutively enrolled in this prospective open-label case series. All patients were treated with an off-label 2-mg intravitreal injection of aflibercept. After the first injection, administration of aflibercept followed an “on demand” pro re nata (PRN) regimen. The primary outcome was change in best-corrected visual acuity (BCVA) score after 12 months.ResultsMean follow-up was 12 months, and the median number of aflibercept injections was 2.0 (range 1–4). Overall, mean BCVA improved from 0.59 ± 0.37 logMAR at baseline to 0.38 ± 0.33 logMAR at 12 months, a change of −0.21 ± 0.23 logMAR (p < 0.0001), and from 70.5 ± 18.5 to 81.1 ± 16.4 letters, a change of 10.6 ± 11.4 (p < 0.0001). Improvements were similar among patients irrespective of previous PDT. The Increase in BCVA was greater in younger patients (aged < 50 years) and those with baseline BCVA of ≤ 75 letters.ConclusionIntravitreal aflibercept in a PRN regimen is effective for the treatment of myopic CNV, with no apparent short-term safety effects. Treated eyes had BCVA gains after 12 months, with a median of two injections.

  • Multimodal imaging and diagnosis of myopic choroidal neovascularization in Caucasians
    Paolo Milani, Amedeo Massacesi, Stefania Moschini, Marco Setaccioli, Ennio Bulone, Gemma Tremolada, Stefano Ciaccia, Elena Mantovani, Daniela Morale, and Fulvio Bergamini

    Informa UK Limited
    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⩽0.001). In eyes with edema or hemorrhage, hyper-reflective foci were more frequent (P⩽0.005). NIR and AF features were indeterminable in 19 (29.2%) and 27 (41.5%) eyes, respectively. The predominant feature was black or grayish on NIR (34/65, 52.3%) and patchy (hypo- and hyperfluorescence was observed) on AF (25/65, 38.4%). FA and SD-OCT correctly detected mCNV in 49 (75.3%) and 48 (73.8%) eyes, respectively, whereas NIR and AF exhibited limited diagnostic sensitivity. Doubtful diagnosis was associated with hyperfluorescent mCNV (P⩽0.001), absence of retinal fluid and epiretinal membrane (P⩽0.05), and presence of macular chorioretinal atrophy (P⩽0.01). Conclusion Tomographic, angiographic, AF, and NIR features of mCNV are described in this study. Combination of SD-OCT and FA is recommendable for diagnosis.

  • A randomized trial of intravitreal bevacizumab vs. ranibizumab for myopic CNV
    Alfredo Pece, Paolo Milani, Carla Monteleone, Costantino John Trombetta, Giuseppe De Crecchio, Giuseppe Fasolino, Domenica Matranga, Salvatore Cillino, and Maria Vadalà

    Springer Science and Business Media LLC
    AimsThe aim was to compare the efficacy of intravitreal therapy with bevacizumab and ranibizumab for choroidal neovascularization (CNV) in pathologic myopia (PM).MethodsThis was a prospective multicenter randomized nonblinded trial.ResultsIn seven centers, 78 eyes were randomized 1:1 to treatment with bevacizumab (group B, 40 eyes) or ranibizumab (group R, 38 eyes) given with an “on demand” regimen (PRN). The mean follow-up was 19 months (SD 2, range 12–24). The mean BCVA at baseline was 0.60 logMAR (20/80 Snellen equivalent, Seq) and 50 letter score (ls). Mean final BCVA was 0.51 LogMAR (20/63 Seq) and 57 ls (p = 0.0009 and p = 0.0002, respectively). In group B, mean basal BCVA was 0.52 logMAR (20/63 Seq) and 54 ls, and final BCVA was 0.51 logMar (20/63 Seq) and 57 ls. In group R, mean basal BCVA was 0.62 logMAR (20/80 Seq) and 45 ls, and the final values were 0.50 logMAR (20/63 Seq) and 58 ls. Statistical comparison of the two groups showed no significant difference (logMAR p = 0.90 and letters p = 0.78). Multivariate analysis showed no influence of age or previous photodynamic treatment (PDT) on final visual changes. The mean number of treatments in the first year was 2.7 in group B and 2.3 in group R (p = 0.09).ConclusionMyopic CNV equally benefits from on-demand intravitreal injection of either bevacizumab or ranibizumab; the therapeutic effect is independent of previous PDT and age.

  • Imaging of naive myopic choroidal neovascularization by spectral-domain optical coherence tomography
    Paolo Milani, Alfredo Pece, Luisa Pierro, and Fulvio Bergamini

    S. Karger AG
    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.

  • Sensitivity of fluorescein angiography alone or with SD-OCT for the diagnosis of myopic choroidal neovascularization
    Paolo Milani, Amedeo Massacesi, Marco Setaccioli, Stefania Moschini, Elena Mantovani, Stefano Ciaccia, and Fulvio Bergamini

    Springer Science and Business Media LLC
    BackgroundMyopic 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.MethodsIn this retrospective study, two authors reviewed the charts and images of patients with recent (<30 days) vision deterioration, pathologic myopia, axial length >26 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.ResultsA 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, p < 0.001), 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.ConclusionsOn the basis of FA alone, active mCNV can be misdiagnosed. The use of SD-OCT combined with FA should therefore be strongly considered.

  • Only first intravitreal bevacizumab injection achieves statistically significant visual improvement in naïve myopic choroidal neovascularization
    Paolo Milani, Massacesi, Ciaccia, Setaccioli, Moschini, and Bergamini

    Informa UK Limited
    Background 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.

  • Spectral domain OCT and autofluorescence imaging of unilateral acute idiopathic maculopathy
    Paolo Milani, Viviana Cacioppo, Giulia Raimondi, and Antonio Scialdone

    SAGE Publications
    Purpose To report imaging findings of unilateral acute idiopathic maculopathy (UAIM). Methods In this observational case report, the Spectralis acquisition system (Heidelberg Engineering, Germany), which includes spectral domain optical coherence tomography (OCT), multiple autofluorescence (AF), fluorescein angiography (FA), and indocyanine green (ICG) angiography, was used for monitoring onset and evolution of UAIM. Results A well-defined, bullous macular lesion was evident on color pictures, infrared imaging (IR), and AF. Fluorescein angiography and ICG similarly showed early hypofluorescence of the lesion and, exclusively on FA, mild staining. Notably, the definition and limits of the detachment were clearly identifiable on late-phase ICG, and formed a hypocyanescent area. Spectral domain OCT disclosed severe retinal pigment epithelium (RPE) but not neurosensory detachment; the distinction between the photoreceptors inner/outer segment line was nonapparent for the entire length of the lesion. At 7-week follow-up, visual acuity improved to 20/20, with resolution of the exudative detachment. Autofluorescence and FA imaging indicated normalization, and only IR showed the boundaries of the lesion as still identifiable. Infrared imaging also showed a central granular feature, suggesting persistent choroid and pigment alteration. Indocyanine green angiography still evidenced the early hypofluorescent halo that became more evident in the late phases without any staining of the dye. Tomography depicted a reconstituted fovea, in which the outer limiting membrane and the inner/outer segment junction returned detectable. Conclusions Comprehensive evaluation of UAIM by AF, FA, ICG, and spectral domain OCT disclosed involvement of RPE, the neuroretina, and the choroid in the pathogenesis of the disease. Despite functional recovery, choroidal rather than retinal alteration could persist.

  • Biomicroscopy versus optical coherence tomography screening of epiretinal membranes in patients undergoing cataract surgery
    Paolo Milani, Giulia Raimondi, Daniela Morale, and Antonio Scialdone

    Ovid Technologies (Wolters Kluwer Health)
    Purpose: The purpose of the study is the evaluation and comparison of the relative incidence of epiretinal membrane in patients undergoing cataract surgery diagnosed with biomicroscopy versus those diagnosed with optical coherence tomography imaging (Stratus). Methods: This prospective study evaluated 146 eyes of patients referred for cataract surgery. Considering biomicroscopic fundus appearance assessed by two examiners and OCT, the following findings were considered to indicate positivity for epiretinal membranes: biomicroscopic evidence of cellophane macular reflex, biomicroscopic evidence of macular pucker, and OCT thickening of the vitreoretinal interface with or without loss of the foveal depression. Positivity (metamorphopsia) to original Amsler test was also noted. Results: Patient mean age was 72.8 ± 9.1 years. Optical coherence tomography revealed 17 eyes with macular pucker (11.6%) and 21 with cellophane macular reflex (14.4%) and, hence, a total of 38 eyes with epiretinal membrane (26%; confidence interval, 18.9–33.1%). Biomicroscopy evaluation overlooked 14 affected eyes, or 9.6% of the eyes examined. False negatives, that is, eyes affected by epiretinal membrane (cellophane macular reflex or macular pucker) and not detected biomicroscopically were 36.8% (confidence interval, 21.5–52.2.7%) and false positives were 1.9% (confidence interval, 0–4%). Amsler test was positive in 7 (18.4%) of the 38 affected eyes. Conclusion: This study finds that patients undergoing cataract surgery may present with epiretinal membrane that are better detected by optical coherence tomography rather than by biomicroscopy. Optical coherence tomography was more sensitive both for eyes with cellophane macular reflex and for those with macular pucker. The use of this instrument before surgery can therefore be considered.

  • Spectral domain OCT versus time domain OCT in the evaluation of macular features related to wet age-related macular degeneration
    Paolo Milani, Pierro, Zampedri, Gagliardi, and Alfredo Pece

    Informa UK Limited
    Background The aim of this study was to compare the agreement between spectral domain optical coherence tomography (SD OCT) and time domain stratus OCT (TD OCT) in evaluating macular morphology alterations in wet age-related macular degeneration (AMD). Methods This retrospective study was performed on 77 eyes of 77 patients with primary or recurring subfoveal choroidal neovascularization secondary to AMD. All patients underwent OCT examination using Zeiss Stratus OCT 3 (Carl Zeiss Meditec Inc, Dublin, CA) and Opko OTI Spectral SLO/OCT (Ophthalmic Technologies Inc, Toronto, Canada). In all radial line scans, the presence of intraretinal edema (IRE), serous pigment epithelium detachment (sPED), neurosensory serous retinal detachment (NSRD), epiretinal membrane (EM), inner limiting membrane thickening (ILMT), and hard exudates (HE) were evaluated. The degree of matching was quantified by Kappa measure of agreement. Results The percentage distribution of TD OCT findings versus SD OCT findings was: IRE 36.3% versus 77.9%, sPED 57.1% versus 85.7%, NSRD 38.9% versus 53.2%, EM 10.5% versus 26.3%, ILMT 3.8% versus 32.4%, and HE 6.4% versus 54.5%. The agreement was as follows: sPED: kappa value 0.15; NSRD: kappa value 0.61; IRE: kappa value 0.18; EM: kappa value 0.41; ILMT: kappa value 0.02; HE: kappa value 0.06. Conclusion The agreement in the evaluation of macular lesions between the two techniques is poor and depends on the lesion considered. SD OCT allows better detection of the alterations typically related to choroidal neovascularization such as IRE, PED, ILM thickening, and HE. Consequently its use should be strongly considered in patients with wet AMD.

  • Retinal photoreceptor focal disruption secondary to accidental Nd:YAG laser exposure
    Paolo Milani, Luisa Pierro, Alfredo Pece, Valerio Marino, and Antonio Scialdone

    Springer Science and Business Media LLC
    Retinal injuries caused by accidental laser exposure include retinal or vitreous hemorrhages, macular holes and edema. We describe the imaging of a bilateral macular lesion secondary to accidental Nd:YAG laser exposure. Observational case report. We performed color photography, fluorescein angiography and autofluorescence (AF) with a scanning laser ophthalmoscope, as well as time-domain and spectral-domain optical coherence tomography (OCT). After accidental exposure to a 1064 nm Nd:YAG laser, a patient experienced blurred vision in the left eye (LE) with visual acuity of 20/60. Color, fluorescein angiography and OCT imaging showed a retinal hemorrhage in the foveal area of the left eye and in the inferomacular region of the asymptomatic right eye. Steroid therapy was then administered, and 5 days later there was rapid improvement with progressive re-absorption of the hemorrhages and functional recovery. At 6 month follow-up, visual acuity was 20/20 in both eyes with unremarkable biomicroscopy, except for focal foveal retinal pigment epithelium (RPE) atrophy in the LE. In comparison to previous hemorrhages, OCT could visualize focal disruption of the photoreceptor IS/OS junction in both eyes. Due to different macular pigment distribution and lesion localization, 787 nm near-infrared AF depicted a small hypofluorescent spot in both eyes, whilst at 488 nm AF a black spot became evident in the right eye only. Despite the re-absorption of foveal hemorrhage and the functional recovery, AF and OCT imaging highlighted the persistence of small focal disruptions of the photoreceptor outer segments and RPE.

  • A long-term study of photodynamic therapy with verteporfin for choroidal neovascularization at the edge of chorioretinal atrophy in pathologic myopia
    Alfredo Pece, Paolo Milani, Vincenzo Isola, and Luisa Pierro

    S. Karger AG
    Purpose: To evaluate the effects of verteporfin photodynamic therapy (PDT) on choroidal neovascularization (CNV) at the edge of chorioretinal atrophy in eyes with pathologic myopia. Procedures: Twenty eyes of 20 consecutive patients were treated according to Verteporfin in Photodynamic Therapy criteria. The patients were divided into 3 groups based on CNV location and were followed up with clinical and fluorescein angiographic examinations to evaluate visual acuity (VA) changes and number of treatments. Results: The mean follow-up was 35 months. In group 1 (n = 8; subfoveal CNV), VA declined from 20/73 (0.56 ± 0.26 logMAR) to 20/115 (0.76 ± 0.30 logMAR; p = 0.192). In group 2 (n = 6; juxtafoveal CNV), VA improved from 20/69 (0.54 ± 0.25 logMAR) to 20/46 (0.36 ± 0.16 logMAR; p = 0.176). In group 3 (n = 6; extrafoveal CNV), VA worsened from 20/50 (0.40 ± 0.21 logMAR) to 20/91 (0.66 ± 0.49 logMAR; p = 0.292). Conclusions: PDT showed inhibitory effects on myopic CNV arising at the edge of chorioretinal atrophy, especially in young adult myopic eyes with juxtafoveal neovascular membranes.

  • Autofluorescence imaging of cystoid macular edema in diabetic retinopathy
    Alfredo Pece, Vincenzo Isola, Frank Holz, Paolo Milani, and Rosario Brancato

    S. Karger AG
    Aim: Our purpose was to assess fundus autofluorescence (FAF) images in patients with diabetic retinopathy and cystoid macular edema (CME) and their correlation with fluorescein angiography (FA) and optical coherence tomography (OCT) findings. Methods: Sixty-eight eyes of 34 consecutive patients with diabetic retinopathy were examined with autofluorescence imaging using a confocal scanning laser ophthalmoscope, FA and OCT. The eyes were divided into 2 groups, group 1 with CME and group 2 without. Results: In the 44 eyes of group 1 (65% of the series), we identified 3 patterns of FAF: (1) multicystic increased FA (57%), (2) a single cyst of increased FAF (16%), (3) combined single- and multicystic increased FAF (27%). FA and OCT gave a positive correlation between cystic increased FAF and CME (r = 0.95; p = 0.001). Visual acuity loss was not correlated with the size of the cystic area (p = 0.83), but it was related to significant macular thickening (p = 0.007). Conclusions: Confocal scanning laser ophthalmoscopy can selectively visualize autofluorescent, multilobulated spaces in eyes with diabetic CME. Even if OCT remains preferable for evaluating macular thickening and cysts, FAF might be another useful easy test to rapidly distinguish this entity noninvasively and with no risk.