Luisa Frizziero

In Vivo Detection of Choroidal Abnormalities Related to NF1: Feasibility and Comparison With Standard NIH Diagnostic Criteria in Pediatric Patients

PURPOSE To evaluate the feasibility of near-infrared (NIR) imaging acquisition in a large sample of consecutive pediatric patients with neurofibromatosis type 1 (NF1), to evaluate the diagnostic performance of NF1-related choroidal abnormalities as a diagnostic criterion of the disease, and to compare this criterion with other standard National Institutes of Health (NIH) diagnostic criteria. METHODS A total of 140 consecutive pediatric patients (0-16 years old) affected by NF1 (at least two diagnostic criteria), 59 suspected (a single diagnostic criterion), and 42 healthy subjects (no diagnostic criterion) were consecutively included. Each patient underwent genetic, dermatologic, and ophthalmologic examination to evaluate the presence/absence of each NIH diagnostic criterion. The presence of NF1-related choroidal abnormalities was investigated using NIR confocal ophthalmoscopy. Two masked operators assessed Lisch nodules and NF1-related choroidal abnormalities. RESULTS Neurofibromatosis type 1-related choroidal abnormalities were detected in 72 affected (60.5%) and 1 suspected (2.4%) child. No healthy subject had choroidal abnormalities. Feasibility rate of this sign was 82%. Sensitivity, specificity, and positive and negative predictive values of NF1-related choroidal abnormalities were 0.60, 0.97, 0.98, and 0.46, respectively. Compared with standard NIH criteria, the presence of NF1-related choroidal abnormalities was the third parameter for positive predictive value and the fourth for sensitivity, specificity, and negative predictive value. Compared with Lisch nodules, NF1-related choroidal abnormalities were characterized by higher specificity and positive predictive value. The interoperator agreement for Lisch nodules and NF1-related choroidal abnormalities was 0.67 (substantial) and 0.97 (almost perfect), respectively. The use of this sign moved one patient from the suspected to the affected group (0.5%). CONCLUSIONS Neurofibromatosis type 1-related choroidal abnormalities represent a new diagnostic sign in NF1 children. The main advantage of this sign seems the theoretical possibility to anticipate NF1 diagnosis, whereas the main obstacle is the cooperation required by very young patients.

HYPERREFLECTIVE INTRARETINAL SPOTS IN RADIATION MACULAR EDEMA ON SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY.

Purpose: To better pathophysiologically characterize macular edema secondary to eye irradiation, analyzing the presence of optical coherence tomography (OCT) hyperreflective spots. Methods: Twenty-five consecutive eyes affected by radiation maculopathy, secondary to irradiation for a primary uveal melanoma, without macular involvement in the irradiation field, were consecutively enrolled. All subjects underwent full ophthalmologic examination, including fluorescein angiography, color fundus photography, and spectral domain OCT, even in en face modality. Optical coherence tomography central subfield thickness was stratified into the following 3 categories: <400 &mgr;m, 400 to 600 &mgr;m, and >600 &mgr;m. Spectral domain OCT images were analyzed to measure and localize hyperreflective spots by two independent masked graders. Results: Hyperreflective spots were documented in all eyes (100%). Hyperreflective spots significantly increased in number according to OCT central subfield thickness (<400 &mgr;m, 400–600 &mgr;m, >600 &mgr;m, P < 0.05). The intergrader agreement was at least substantial for all measurements (intraclass correlation coefficient: 0.80). Conclusion: Spectral domain OCT documents discrete intraretinal reflectivity changes (hyperreflective spots) in all (studied) eyes affected by radiation maculopathy. Hyperreflective spots increase in number with increasing central subfield thickness and could be considered as a new clinical biomarker of intraretinal inflammation in patients affected by macular edema secondary to irradiation for uveal melanoma.

Retinal Vascular Abnormalities In A Large Cohort Of Patients Affected By Neurofibromatosis Type 1: A Study Using Optical Coherence Tomography Angiography.

Purpose: To evaluate the prevalence, the vascular features, and the clinical diagnostic implication of retinal vascular abnormalities (RVAs) associated with neurofibromatosis Type 1 (NF1) in a large cohort of patients. Methods: Two hundred and ninety-four patients affected by NF1 were consecutively enrolled. The presence of RVAs was detected by means of infrared confocal scanning laser ophthalmoscopy images. Three hundred age- and race-matched healthy subjects were enrolled as a healthy control group. Fluorescein angiography, indocyanine green angiography, and optical coherence tomography angiography were also performed in patients with RVAs. Results: Retinal vascular abnormalities were detected in 18 patients with NF1 (6.1%) and in none of the healthy subjects. Retinal vascular abnormalities appeared in all cases as well-defined, small, tortuous retinal vessels with a spiral aspect, originating from small tributaries of retinal veins. The presence of RVAs did not correlate with the presence of other specific ocular or systemic NF1 features (P > 0.05). On optical coherence tomography angiography, RVAs appeared as an isolated tortuous vessel of the superficial vascular plexus in all cases, associated with localized anomalous crowded and congested capillary network of the deep vascular plexus in 75% of cases. Conclusion: Retinal vascular abnormalities are present in a limited proportion of patients affected by NF1 and can be considered an additional distinctive sign of the disease.

Topical 1% 5-fluoruracil as a sole treatment of corneoconjunctival ocular surface squamous neoplasia: long-term study

Aims To report long-term clinical outcome of topical 1% 5-fluoruracil (5-FU) as a sole treatment of ocular surface squamous neoplasia (OSSN). Methods 41 patients affected by OSSN were included. Each patient underwent full ophthalmological examination at baseline, with cytological or histological confirmation. Patients were treated by topical chemotherapy with 1% 5-FU four times a day for 4 weeks. One course was defined as 4 weeks of topical chemotherapy. Adjunctive courses were administered after 1 month of chemotherapy-free interval. Results Mean follow-up was 105±32 months (range 60–171 months). Complete tumour regression was achieved in 34 cases (83%) after a mean of 1.5 courses (range, 1–3 courses). Univariate analysis revealed that complete response was significantly related to tumour thickness <1.5 mm (p=0.005), lack of fornix or tarsal involvement (p=0.015 and p=0.009, respectively) and the absence of multifocality (p=0.002). Histopathological diagnosis (intraepithelial neoplasia vs squamous cell carcinoma, p=0.019) and American Joint Committee on Cancer (AJCC) classification (T1 vs T2 or T3) (p=0.028) were also related to incomplete tumour response. In a multivariate analysis, just tumour thickness >1.5 mm (p=0.045) and multifocality (p=0.023) were correlated with incomplete tumour response. Transient and reversible low-to-mild local side effects were documented in 19 (48%) eyes. Conclusion Topical 5-FU, as a sole therapy, is a long-term safe and effective treatment for patients affected by preinvasive OSSN and for a limited proportion (50%) of invasive OSSN.

Repeatability and Reproducibility of Foveal Avascular Zone Area Measurement on Normal Eyes by Different Optical Coherence Tomography Angiography Instruments

Purpose: To compare the foveal avascular zone (FAZ) area measurements produced by different optical coherence tomography angiography (OCTA). Methods: Healthy enrolled volunteers underwent OCTA using 2 different devices: Spectralis HRA+OCTA (Heidelberg Engineering, Heidelberg, Germany) and RS-3000 Advance (Nidek, Gamagori, Japan). Two graders measured FAZ in both superficial (SCP) and deep (DCP) retinal capillary plexuses. The SCP and DCP en face images were visualized automatically segmenting 2 separate slabs defined by the arbitrary segmentation lines created by the software of each OCT device. One grader repeated each measure twice. Results: Fifty-nine eyes were included. The mean FAZ was 0.33 ± 0.09 mm2 at the SCP and 0.57 ± 0.17 mm2 at the DCP measured with RS-3000 versus 0.30 ± 0.08 and 0.35 ± 0.08 mm2, respectively, measured with Spectralis. The measurements of the 2 devices were significantly different (p < 0.0001). The intraoperator agreement was excellent at the SCP (intraclass correlation coefficient, ICC: 0.97 with Spectralis and 0.96 with RS-3000). At the DCP, it was good with Spectralis and fair with RS-3000 (ICC: 0.85 and 0.64, respectively). The interoperator agreement was excellent for Spectralis and good for RS-3000 at the SCP (ICC: 0.97 and 0.93, respectively). It was good at the DCP with both devices (ICC: 0.74 with RS-3000 and 0.81 with Spectralis). Conclusions: FAZ measurements obtained with different OCTA devices differ. These findings should be considered in follow-up studies of patients with retinal vascular diseases.

Pharmacotherapy and Immunotherapy of Conjunctival Tumors

Abstract: Conjunctiva and cornea tumors represent a large spectrum of conditions ranging from benign lesions to aggressive and life‐threatening malignancies. Topical pharmacotherapies and immunotherapies have recently acquired a relevant role in the management of conjunctival tumors and, in the past 2 decades, there has been a shift from surgery alone toward the use of these agents, both as a sole therapy or as adjunct to surgery (before or after surgery). The 3 main agents that have been used for topical medical treatment of conjunctival tumors are mitomycin C, 5‐fluorouracil, and interferon‐&agr;2b. Advantages of topical pharmacotherapies and immunotherapies include the ability to treat the entire ocular surface and prevention of surgical side effects and complications. The aim of this review is to summarize the current use of topical pharmacotherapy and immunotherapy in the management of conjunctival tumors.

Peripapillary vascular changes in radiation optic neuropathy: an optical coherence tomography angiography grading

Aims To investigate peripapillary vascular changes secondary to radiation optic neuropathy (RON) using optical coherence tomography angiography (OCT-A) and to propose a clinical grading of RON based on OCT-A findings. Methods Thirty-four patients affected by RON were consecutively included. Each patient underwent best corrected visual acuity measurement (ETDRS score) and OCT-A (Nidek RS-3000 Advance device, Nidek, Gamagori, Japan). The radial peripapillary capillary plexus (RPCP) and the entire peripapillary capillary bed (EPCB) were analysed. Quantitative analysis of the OCT-A images was performed using open-source available ImageJ software (National Institutes of Health, Bethesda, Maryland, USA). Qualitative analysis based on the proposed clinical grading (Grades 0–4) was also performed by two masked graders. Results RON clinical (qualitative) classification based on RPCP correlated with the quantitative RPCP perfusion analysis (P=0.0001). RON clinical classification based on RPCP statistically correlated with ETDRS score (P=0.001). RON clinical classification based on EPCB also correlated with the quantitative EPCB perfusion analysis and ETDRS score (P=0.02 and P=0.01, respectively). Compared with the clinical classification based on EPCB, the qualitative classification based on RPCP reached a higher intergrader agreement (0.96 and 0.86, respectively). Conclusion OCT-A can be used to detect RPCP abnormalities and to clinically classify RON with a high interexaminer agreement. The proposed clinical classification is supported by the quantitative analysis based on the use of specific images elaboration techniques and correlates with visual acuity of the examined eyes.

Intraocular Metastases Secondary to Breast Carcinoma Correlates With Upregulation of Estrogen and Progesterone Receptor Expression in the Primary Tumor.

PURPOSE To compare estrogen (ER), progesterone (PR), and human epidermal growth factor-2 (HER2) receptor expression in the primary tumor of patients affected by choroidal metastases from breast carcinoma (BC) versus those with extraocular metastases. METHODS Eighteen consecutive patients affected by choroidal metastases from BC were included. We defined ER, PR, and HER2 positivity of the primary tumor following standard guidelines. Breast carcinoma molecular subtypes were also identified (luminal A, luminal B, HER2-enriched, and triple negative). Forty consecutive patients affected by metastatic BC without choroidal involvement were included as a control group. RESULTS The study group and the control group were similar for age, sex, race, histopathologic classification of the primary tumor (ductal, lobular, others), and American Joint Committee on Cancer Tumor-Node-Metastasis stage at the time of primary tumor diagnosis (P > 0.05). Patients affected by choroidal metastases from BC showed a significantly higher expression of ER (P = 0.009) and PR (P = 0.018) receptors in the primary tumor compared with nonchoroidal metastatic BC. Across all patients, the luminal B molecular subtype was related to the presence of choroidal involvement (P = 0.003). Considering luminal tumors only, the luminal B subclassification was also related to the presence of choroidal involvement (P = 0.009). CONCLUSIONS Choroidal metastases from BC are associated with ER and PR expression in the primary tumor and the luminal B molecular subtype.

Early OCT angiography changes of type 1 CNV in exudative AMD treated with anti-VEGF

Aims To investigate, with optical coherence tomography angiography (OCTA), short-term changes of type 1 choroidal neovascularisation (CNV), secondary to exudative age-related macular degeneration, after anti-vascular endothelial growth factor (VEGF) treatment. Methods Patients affected by type 1 CNV treated with intravitreal anti-VEGF were consecutively enrolled. All patients underwent OCTA examination before and 48 hours after anti-VEGF treatment. Quantitative and qualitative vascular and morphological macular changes were evaluated. Results Sixteen eyes were included (11 treated with aflibercept and 5 with ranibizumab). Both CNV mean area and pigment epithelium detachment significantly reduced (p=0.0004 and p=0.0007, respectively) after treatment. Cystoid macular oedema (four eyes) decreased in all cases. Neuroretinal detachment (13 eyes) decreased in 85% of cases (11 eyes). Fine CNV vessels density decreased in 75% (12 eyes), whereas larger CNV vessels density remained stable in 66.7% (10 eyes), choroidal flow void signal (7 eyes at baseline) increased in 42.9% (3 eyes) of them and remained stable in 57.1% (4 eyes). Interoperator reproducibility for OCT examination was good for all measurements (intraclass correlation coefficient>0.65). Conclusion Early remodelling of type 1 CNV network after treatment may be non-invasively and reproducibly analysed by means of OCTA. Choroidal perfusion impairment, choroidal flow void signal, surrounding CNV may change during treatment.

Correlation of peripapillary retinal nerve fibre layer thickness with visual acuity in paediatric patients affected by optic pathway glioma

To evaluate peripapillary retinal nerve fibre layer (RNFL) thickness, measured by spectral‐domain optical coherence tomography (SD‐OCT), as a surrogate of visual function in a population of paediatric patients affected by optic pathway glioma (OPG) associated with neurofibromatosis type 1 (NF1).