Giacomo Miglionico

Optical Coherence Tomography in the Diagnosis of Optic Pathway Gliomas

PURPOSE To compare visual function assessment, optic disc evaluation by indirect ophthalmoscopy, and retinal nerve fiber layer analysis by optical coherence tomography (OCT) for the screening of optic pathway gliomas in pediatric patients (2-15 years old) affected by neurofibromatosis type 1. METHODS Fifty-seven consecutive patients with neurofibromatosis type 1 with recent (<6 months) orbital/brain magnetic resonance images (MRI) were included. Patients underwent visual function assessment (Hyvarinen symbols chart and/or Snellen charts) and optic disc evaluation by indirect ophthalmoscopy performed by experienced, masked pediatric ophthalmologists. Spectral domain OCT was performed to assess retinal nerve fiber layer. RESULTS Fifteen of 57 enrolled patients (26%) were affected by MRI-proven optic pathway gliomas. Visual function assessment, optic disc evaluation, and retinal nerve fiber layer analysis by OCT were feasible in 84%, 95%, and 88% of patients, respectively. Visual function assessment, retinal nerve fiber layer analysis, and optic disc evaluation results correlated with the presence of optic pathway gliomas (P = 0.007, P < 0.0001, and P = 0.03, respectively). Specificity and negative predictive value of each test were statistically significant in detecting optic pathway glioma (P < 0.0001), whereas only retinal nerve fiber layers analysis reached statistically significant sensitivity and positive predictive value (P = 0.0386). CONCLUSIONS Retinal nerve fiber layer analysis assessment using spectral domain OCT is superior to visual function assessment and optic disc evaluation as a clinical screening tool for optic pathway gliomas.

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.

Intravitreal Triamcinolone Versus Intravitreal Bevacizumab in the Treatment of Exudative Retinal Detachment Secondary to Posterior Uveal Melanoma

PURPOSE To evaluate the efficacy and safety of prompt intravitreal triamcinolone acetonide injection (4 mg/0.1 mL) vs intravitreal bevacizumab injection (1.25 mg/0.05 mL) compared with observation in the management of extensive exudative retinal detachment secondary to posterior uveal melanoma. DESIGN Retrospective, nonrandomized, interventional case series. METHODS setting: Institutional. patients: Ninety-six patients affected by posterior uveal melanoma with large exudative retinal detachment (>10 mm in largest basal diameter) were included. intervention: Patients received intravitreal triamcinolone acetonide (32 eyes) or intravitreal bevacizumab (32 eyes) at plaque removal. Thirty-two patients served as controls (observation group). All groups were matched for age, sex, initial tumor thickness and largest basal diameter, largest exudative retinal detachment basal diameter, tumor location, and Bruch membrane rupture. Patients underwent monthly follow-up examinations in the first 6 months and every 3 months thereafter. Follow-up was longer than 24 months. main outcome measure: Exudative retinal detachment resolution (B-scan ultrasonography), steroid-induced cataract, steroid-induced increased IOP. RESULTS Follow-up was 37 ± 7 months. Marked exudative retinal detachment regression was documented in 22 (69%) intravitreal triamcinolone acetonide-treated vs 11 (34%) intravitreal bevacizumab-treated and 9 (28%) untreated eyes (P = .0007 and P = .0001, respectively). No statistical significance was found between intravitreal bevacizumab group vs observation group (P = .45) Steroid-induced cataract was observed in 4 intravitreal triamcinolone acetonide-treated patients (12%). Neither steroid-induced increased IOP nor other short- or long-term side effects were documented. CONCLUSION Intraoperative intravitreal triamcinolone acetonide injection induces earlier and marked exudative retinal detachment resolution after brachytherapy of posterior uveal melanoma. Risk and benefit should be balanced vs steroid-induced cataract.

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.

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 retinal and choroidal OCT and OCT angiography signs of inflammation after uncomplicated cataract surgery

Purpose To evaluate, by means of optical coherence tomography (OCT) and OCT angiography (OCTA), early retinal, choroidal and macular perfusion changes induced by a local inflammatory reaction secondary to uncomplicated cataract surgery. Methods Selected eyes undergoing cataract surgery were enrolled in a prospective study. OCT and OCTA were performed before cataract surgery (T0) and at day: 1 (T1), 7 (T7), 30 (T30) and 90 (T90). Inner (IR) and outer retinal (OR) volumes, choroidal volume, hyper-reflective retinal spots (HRS) in IR and OR changes were measured at OCT. Macular perfusion was analysed in superficial (SCP), intermediate (ICP) and deep retinal capillary plexuses (DCP). Results Nine eyes of nine selected patients were consecutively enrolled. Mean IR volume changed after surgery (p=0.0001), increasing progressively from 4.391±0.231 mm³ at T0 to 4.573±0.241 mm³ at T30, p=0.0002. Both mean OR and choroidal volume increased, mainly at T30, but not significantly (p=0.4360 and p=0.2300, respectively). Mean HRS changed during follow-up, increasing at first in IR and later in OR (at T1 and T7, respectively, both p<0.0001). Macular ICP and DCP perfusion increased at T1, whereas macular SCP perfusion did not change. At T90, all OCT and OCTA parameters had almost reached baseline levels. Conclusions The increase of HRS at first in IR and later in OR seems to confirm their inflammatory nature. Early OCTA changes (underline) underscore a selective susceptibility of DCP and ICP to a localised inflammatory reaction induced by cataract surgery.

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).