Choroidal Abnormalities in Pediatric NF1: A Cohort Natural History Study.

The purpose of this study was to assess the long-term natural history of choroidal abnormalities (CAs) in a large pediatric neurofibromatosis type 1 (NF1) population, quantifying their progression in number and dimensions. Pediatric patients (<16 years old) affected by NF1 with a minimum follow-up of 3 years with at least one CA in one eye were consecutively recruited. Near-infrared (NIR) imaging was performed to identify CAs, which were quantified in number and size. The CAs area and perimeter were normalized for the optic disc dimensions to avoid possible bias related to the growing process of the eye. Ninety-nine eyes of 53 patients were evaluated. The CAs number, area and perimeter significantly increased during follow-up (p < 0.0001 for each parameter). The patient age at baseline was inversely correlated with the CAs number over time (coefficient = −0.1313, p = 0.0068), while no correlation was found between the patient age and CAs progression in size. In conclusion, we provide evidence that, in NF1 pediatric patients, CAs change over time, increasing both in number and dimensions, independently from the physiological growth of the eye. While the increase of the CAs number occurs particularly at an earlier age, the increase in the CAs dimensions is a slow process that remains constant during childhood.

RETINAL VASCULAR ABNORMALITIES RELATED TO NEUROFIBROMATOSIS TYPE 1: Natural History and Classification by Optical Coherence Tomography Angiography in 473 Patients.

PURPOSE: To analyze and classify neurofibromatosis Type 1 (NF1)-related retinal vascular abnormalities (RVAs), their natural history and correlation with disease severity, in a large cohort of patients. METHODS: This was an observational longitudinal study with prospective enrollment. Four hundred and seventy-three patients affected by NF1 and 150 age-matched healthy subjects were consecutively enrolled. Retinal vascular abnormalities were detected by means of near-infrared reflectance and studied by optical coherence tomography angiography. The superficial vascular plexus and the deep vascular complex (DVC) were quantitatively and qualitatively analyzed. RESULTS: We identified RVAs in 82 of 473 (17%) NF1 patients, but in none of the 150 healthy subjects. A comparison revealed that NF1 patients with RVAs showed a higher number of NF1 diagnostic criteria (4.3 ± 1.5 vs. 3.9 ±1.5, respectively; P = 0.02) than patients without RVAs. Three different RVA types were identified on optical coherence tomography angiography: macrovascular angiomatosis of the sole superficial vascular plexus; macrovascular angiomatosis of the superficial vascular plexus combined with microvascular angiomatosis of the deep vascular complex; and combined macrovascular angiomatosis of both superficial vascular plexus and deep vascular complex. The prospective analysis of optical coherence tomography angiography images showed no significant longitudinal evolution of RVAs (mean follow-up: 3.7 ± 2.8 years). A single patient developed a de novo single RVA, and two RVAs showed detectable changes during follow-up. CONCLUSION: In NF1 patients, RVAs are a characteristic sign that correlates with a more severe systemic disease expression, usually remaining stable during time. Optical coherence tomography angiography allows for the identification of different RVAs subtypes.

Optical coherence tomography and color fundus photography in the screening of age-related macular degeneration: A comparative, population-based study.

PURPOSE: To analyze the individual value and the contribution of color fundus photography (CFP) and optical coherence tomography (OCT) in the screening of age-related macular degeneration (AMD) of an unselected population. METHODS: CFP and OCT images of 15957 eyes of 8069 subjects older than 55 years, obtained during a population-based screening for AMD using a single diagnostic non-mydriatic imaging device, were analyzed by a blinded examiner. The two techniques were preliminary evaluated considering the dichotomous parameter "gradable/ungradable", then gradable images were classified. CFP were graded according to the standardized classification of AMD lesions. OCT images were also categorized considering the presence of signs of early/intermediate AMD, late AMD, or other retinal diseases. Another blinded operator re-graded 1978 randomly selected images (for both CFP and OCT), to assess test reproducibility. RESULTS: Of the 15957 eyes, 8356 CFP (52.4%) and 15594 (97.7%) OCT scans were gradable. Moreover, most of the eyes with ungradable CFP (7339, 96.6%) were gradable at OCT. AMD signs were revealed in 7.4% of gradable CFP and in 10.4% of gradable OCT images. Moreover, at OCT, AMD signs were found in 1110 (6.9%) eyes whose CFP were ungradable or without AMD (847 and 263 eyes, respectively). The inter-operator agreement was good for the gradable versus ungradable parameter, and optimal for the AMD grading parameter of CFP. The agreement was optimal for all OCT parameters. CONCLUSIONS: OCT provided gradable images in almost all examined eyes, compared to limited CFP efficiency. Moreover, OCT images allowed to detect more AMD eyes compared to gradable photos. OCT imaging appears to significantly improve the power of AMD screening in a general, unselected population, compared to CFP alone.

IDENTIFICATION AND CLASSIFICATION OF MACULAR MORPHOLOGIC BIOMARKERS RELATED TO VISUAL ACUITY IN RADIATION MACULOPATHY: A Multimodal Imaging Study.

PURPOSE: To identify and classify, by a multimodal imaging approach, the most relevant macular morphologic biomarkers related to visual acuity in patients affected by radiation maculopathy secondary to brachytherapy. METHODS: Fifty-one consecutive patients previously treated with Iodine-125 brachytherapy because of uveal melanoma were enrolled. Each patient underwent full ophthalmologic examination including best-corrected visual acuity and multimodal macular imaging analysis. Macular morphological parameters were processed by a stepwise selection analysis. RESULTS: Three macular parameters were identified as the most relevant macular morphologic biomarkers of poor visual acuity: the vertical thickness of the thickest macular cyst (P = 0.0001), the presence of foveal inner segment/outer segment (IS/OS) layer disruption (P = 0.0054), and the presence of foveal retinal pigment epithelium atrophy (0.0884). The intergrader agreement for these morphologic biomarkers was 0.98, 0.92, and 0.92, respectively (interclass correlation coefficient). CONCLUSION: The vertical thickness of the thickest macular cyst, the presence of foveal retinal pigment epithelium atrophy, and IS/OS layer disruption can be used to clinically characterize radiation maculopathy. These parameters allow for separation of the edematous component of radiation maculopathy, which is potentially treatable in early disease stages, from late onset atrophic components, which are theoretically irreversible.

Optic Pathway Glioma in Type 1 Neurofibromatosis: Review of Its Pathogenesis, Diagnostic Assessment, and Treatment Recommendations.

Type 1 neurofibromatosis (NF1) is a dominantly inherited condition predisposing to tumor development. Optic pathway glioma (OPG) is the most frequent central nervous system tumor in children with NF1, affecting approximately 15-20% of patients. The lack of well-established prognostic markers and the wide clinical variability with respect to tumor progression and visual outcome make the clinical management of these tumors challenging, with significant differences among distinct centers. We reviewed published articles on OPG diagnostic protocol, follow-up and treatment in NF1. Cohorts of NF1 children with OPG reported in the literature and patients prospectively collected in our center were analyzed with regard to clinical data, tumor anatomical site, diagnostic workflow, treatment and outcome. In addition, we discussed the recent findings on the pathophysiology of OPG development in NF1. This review provides a comprehensive overview about the clinical management of NF1-associated OPG, focusing on the most recent advances from preclinical studies with genetically engineered models and the ongoing clinical trials.

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.

PURPOSE: 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). METHODS: A total of 38 paediatric patients (66 eyes) affected by MRI-proven OPG were included. Each patient underwent complete ophthalmological examination, including age-appropriate visual acuity (VA) assessment and RNFL analysis by SD-OCT. Visual acuity was classified as normal or pathologic using age-based normative data. Visual acuity was correlated to mean RNFL thickness of the whole peripapillary area and of each single analyzed sector (nasal, superior, temporal, inferior). RESULTS: Visual acuity was normal in 43 (65%) and pathologic in 23 (35%) eyes. Mean parapapillary RNFL thickness of each analyzed sector was significantly lower in eyes with abnormal VA (p < 0.05). The best balanced cut-off value of global RNFL thickness allowing to discriminate between eyes with normal and pathologic VA was 76.25 µm (91%, 76%, 67% and 94% of sensitivity, specificity, positive and negative predicting value, respectively). Considering best balanced cut-off values of other analyzed RNFL sectors, the superior (p = 0.0029) and the inferior (p = 0.0024) sectors reached the higher sensitivity (87% and 87%, respectively) and specificity (81% and 79%, respectively). CONCLUSION: Retinal nerve fibre layer thickness is directly related to VA in children affected by NF1-related OPG, and should be considered as a potential surrogate marker of VA. Retinal nerve fibre layer thickness cut-off values can be used in paediatric patients to discriminate false-positive results obtained by VA measurement.

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.

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.

Retinal Vascular and Neural Remodeling Secondary to Optic Nerve Axonal Degeneration: A Study Using OCT Angiography.

PURPOSE: To investigate the pathophysiologic interrelations between retinal neural and vascular changes, detected by spectral-domain OCT (SD-OCT) and OCT angiography (OCTA), resulting from optic nerve axonal degeneration. DESIGN: Institutional, observational, case-control study with prospective enrollment. PARTICIPANTS: Twenty-six patients affected by optic nerve axonal degeneration secondary to posterior optic pathway glioma (OPG) involving the chiasma, the postchiasmatic visual pathway, or both (but not involving optic nerves) and 24 gender- and age-matched healthy participants were included consecutively. METHODS: Best-corrected visual acuity (Early Treatment Diabetic Retinopathy Study score) was measured and SD-OCT (Heidelberg Engineering, Heidelberg, Germany) and OCTA (Nidek RS-3000 Advance device; Nidek, Gamagori, Japan) were performed. MAIN OUTCOME MEASURES: Peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell complex (GCC), and inner nuclear layer (INL) were analyzed using SD-OCT. The radial peripapillary capillary plexus, full-thickness peripapillary retina vascularization, and the macular superficial plexus (SCP) and deep capillary plexus (DCP) were analyzed using OCTA. RESULTS: Peripapillary retinal nerve fiber layer and GCC thickness were reduced in eyes affected by OPG (P < 0.0001). Radial peripapillary capillary plexus perfusion also was reduced, as well as full-thickness peripapillary retina vascularization (P < 0.01 and P < 0.05, respectively). Macular DCP perfusion was reduced in eyes affected by OPG, whereas macular SCP perfusion did not differ between the 2 groups (P < 0.05 and P > 0.05, respectively). Global pRNFL thickness reduction correlated with the reduction of peripapillary perfusion (P < 0.01). Macular GCC thickness reduction did not correlate with SCP reduction (P > 0.05). The reduction of macular DCP perfusion did not correlate with inner nuclear layer thickness (P > 0.05). CONCLUSIONS: Retinal neural remodeling secondary to optic nerve axonal degeneration resulting from OPG located at or posterior to the chiasm is accompanied by a secondary retinal vascular remodeling involving not only the peripapillary area, but also the macular area (DCP).

Natural history of optic pathway gliomas in a cohort of unselected patients affected by Neurofibromatosis 1.

Optic pathway glioma (OPG) represents the most common central nervous system tumor in children with Neurofibromatosis type-1 (NF1). Although overall survival is usually good, no clear prognostic factors have been identified so far. We assessed the natural history of OPG in a cohort of unselected patients affected by NF1. We retrospectively evaluated 414 consecutive patients affected by NF1 and referred to our NF1 clinic before age 6. Average follow-up was 11.9 years: 52 out of 414 patients had OPG with a total cumulative incidence of 15.4% at age 15 (Kaplan-Meier estimate) and a statistically significant difference according to sex. Brain and orbit MRI was performed in 44.7% of patients: 34.6% for screening purposes and 65.4% because of the presence of neurological, ocular or other symptoms. OPG was diagnosed in 12.5% of cases in the first group, whereas in 36.4% in the latter group (p = 0.001). Clinical management was conservative in most patients, while 8 of them underwent therapy mainly because of visual deterioration. OPG was diagnosed earlier in treated patients, but the difference was not statistically significant. Conversely, all patients who underwent screening MRI had normal visual outcome. In conclusion, OPG location does not correlate with need for treatment; female patients were more frequently affected by OPG but not more frequently treated. OPG diagnosis by screening MRI does not affect the natural history of the tumor.

Intravitreal dexamethasone implant in radiation-induced macular oedema.

AIMS: To evaluate the efficacy and duration of activity of a single intravitreal dexamethasone implant in patients affected by radiation maculopathy. METHODS: Thirteen consecutive eyes of 13 patients affected by radiation maculopathy secondary to eye irradiation for a primary uveal melanoma (Iodine-125 brachytherapy) and treated with a single intravitreal 0.7 mg dexamethasone implant were retrospectively evaluated. Each patient underwent full ophthalmological examination, including fluorescein angiography and spectral domain optical coherence tomography (SD-OCT), even in en-face modality. Follow-up was performed monthly over a 6-month period. RESULTS: At preinjection visit, the median central subfield thickness (CST) by SD-OCT was 407 µm (IQR, 357-524 µm) and the median best-corrected visual acuity (BCVA) was 61 ETDRS score (IQR, 54-67). The median gain of ETDRS letter at 1 month was 6.5 (IQR, 4-15) (p<0.01). The median CST showed a reduction of 120 µm (IQR, 62-134) (p<0.01). Further CST reduction was reported at 2 months' follow-up, with CST stabilisation at 3 months and maintenance of BCVA. At 4, 5 and 6 months' follow-up, all patients presented progressive retinal thickening (p<0.01) and BCVA reduction (p<0.01). No side effects were documented. CONCLUSION: Intravitreal dexamethasone implant reduces macular oedema secondary to radiation maculopathy and also improved visual acuity in a consistent proportion of patients. Signs of macular oedema recurrence may be detected at a median of 4 months after injection.

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.

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.

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 µm, 400 to 600 µm, and >600 µm. 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 µm, 400-600 µm, >600 µm, 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.

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.

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.

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.