Maria Paula Fernandez

First Travel-Associated Congenital Zika Syndrome in the US: Ocular and Neurological Findings in the Absence of Microcephaly.

A 6-day-old female baby with known diagnosis of congenital Zika infection was referred for ophthalmologic examination. The mother (37 years old) was referred for a pruritic rash, conjunctival hyperemia, and malaise at 12 weeks of gestation while still living in Venezuela. Upon arrival to Miami, Zika virus (ZIKV) exposure was confirmed during prenatal screening. At birth, due to the known exposure, a complete congenital ZIKV workup was performed, including brain ultrasound and MRI, which disclosed calcifications in the frontal lobe. Fundus examination revealed a hypopigmented retinal lesion in the left eye that was documented with retinal imaging. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:952-955.].

Ocular Histopathologic Features of Congenital Zika Syndrome

Importance Congenital Zika syndrome (CZS) is known to be associated with severe malformations in newborns. Although microcephaly is the hallmark of this disease, the ocular findings are important given the severe visual impairment that has been observed in these patients. Regardless of the increased number of CZS cases reported, to date, no studies have described the ocular histopathologic findings of this entity. Objectives To evaluate the presence of Zika virus (ZIKV) antigens and describe the associated ocular histopathologic features of 4 cases of CZS. Design, Setting, and Participants In this observational case series performed from June 19, 2015, through April 30, 2017, ocular tissue samples from 4 deceased fetuses with a diagnosis of CZS from the National Institute of Health in Colombia were sent to the Florida Lions Ocular Pathology Laboratory for evaluation. Main Outcomes and Measures The microscopic features of each specimen were described, and immunostaining was performed using a ZIKV NS2B protein antibody. Results Ocular tissue samples from the 4 deceased fetuses (2 female, 2 male) ranging from 21.5 to 29 weeks’ gestation with a diagnosis of CZS were studied. The 4 eyes manifested with pupillary membranes, immature anterior chamber angles, loss of pigment and thinning of the retinal pigment epithelium, choroidal thinning, undifferentiated nuclear layers of the retina, and a perivascular inflammatory infiltrate within the choroid. The optic nerve, present in 2 of the eyes, demonstrated atrophy. Expression of ZIKV antigen was present in the iris in cases 1, 3, and 4; the neural retina and choroid in case 1; and in the optic nerve in case 4. Conclusions and Relevance Loss of retinal pigment epithelium, the presence of a thin choroid, a perivascular choroidal inflammatory infiltrate, and atrophic changes within the optic nerve were consistently present. These findings may be attributed to ZIKV infection and warrant further study.

Fluorescein angiography findings in diffuse retinoblastoma: two case reports with clinicopathologic correlation

Whereas most retinoblastomas are seen as intraocular tumors, the diffuse infiltrating type is distinguished by a horizontal growth along the retina with minimal vertical growth. These findings can resemble other entities and present as a diagnostic challenge. Fluorescein angiography (FA) features of retinoblastoma have been described in the literature; however, to our knowledge, little information is available on the diffuse type. We present FA findings and the clinicopathlogic correlation of 2 patients with diffuse retinoblastoma. Changes observed on FA correlate with the vascular changes observed on histopathology and can therefore be helpful in the diagnosis of atypical retinoblastomas when the clinical presentation is equivocal.

Histopathologic Characterization of the Expression of Vascular Endothelial Growth Factor in a Case of Retinopathy of Prematurity Treated With Ranibizumab

PURPOSE To characterize the expression of vascular endothelial growth factor (VEGF) in a patient with retinopathy of prematurity (ROP) treated with ranibizumab (Case 1) and compare it with a case of ROP without treatment (Case 2), a case of a premature baby without ROP (Case 3), and a case of a baby without history of ROP or prematurity (Case 4). DESIGN Observational case series. METHODS The eyes of the deceased babies were removed postmortem and were sent to the Florida Lions Ocular Pathology Laboratory, where they were processed. The specimens were immunostained using an antibody against VEGF. RESULTS All eyes except for the eyes in Case 4 disclosed positive VEGF staining. Positive staining was present within the nerve fiber layer, inner plexiform layer, and inner and outer nuclear layers and within the spindle-shaped cell population in the vanguard in Case 1. In the posterior pole, positive staining was only observed at the level of the nerve fiber layer. This case also demonstrated less positive staining when compared with Case 2, where positive staining was found within all layers of the retina. CONCLUSION Less VEGF staining was observed within the retina of the eyes treated with ranibizumab when compared with the VEGF staining in Case 2. This supports the idea that anti-VEGF agents are effective in reducing the amount of VEGF present in the retina. Furthermore, the fact that some expression of VEGF remains in the immature retina after injection supports the idea that anti-VEGF agents can suppress uncontrolled neovascularization without completely blocking the vascular drive for the vascularization of the immature retina.

Accidental Nd:YAG Laser–Induced Macular Hole in a Pediatric Patient

After being exposed to an industrial Nd:YAG laser, an 11-year-old boy developed a full-thickness macular hole in the right eye with resultant visual acuity of 20/100. Five months after the initial injury, the vision was stable and the hole was still present. The patient underwent pars plana vitrectomy, internal limiting membrane peeling, and gas tamponade with prone positioning. Three months postoperatively, visual acuity improved to 20/25 with closure of the macular hole; however, there was a focal photoreceptor deficit. A review of the English-language literature identified 15 eyes with similar macular hole injuries after Nd:YAG exposure. Three eyes were surgically managed. While all holes were successfully closed, only two experienced visual improvement.

Expression of hypothalamic neurohormones and their receptors in the human eye

Extrapituitary roles for hypothalamic neurohormones have recently become apparent and clinically relevant, based on the use of synthetic peptide analogs for the treatment of multiple conditions including cancers, pulmonary edema and myocardial infarction. In the eye, it has been suggested that some of these hormones and their receptors may be present in the ciliary body, iris, trabecular meshwork and retina, but their physiological role has yet to be elucidated. Our study intends to comprehensively demonstrate the expression of some hypothalamic neuroendocrine hormones and their receptors within different retinal and extraretinal structures of the human eye. Immunofluorescence, Western blot analysis, and RT-PCR were used to evaluate the qualitative and quantitative expression of Luteinizing Hormone Releasing Hormone (LHRH), Growth Hormone Releasing Hormone (GHRH), Thyrotropin Releasing Hormone (TRH), Gastrin Releasing Peptide (GRP) and Somatostatin as well as their respective receptors (LHRH-R, GHRH-R, TRH-R, GRP-R, SST-R1) in cadaveric human eye tissue and in paraffinized human eye tissue sections. The hypothalamic hormones LHRH, GHRH, TRH, GRP and Somatostatin and their respective receptors (LHRH-R, GHRH-R, TRH-R, GRPR/BB2 and SST-R1), were expressed in the conjunctiva, cornea, trabecular meshwork, ciliary body, lens, retina, and optic nerve.Extrapituitary roles for hypothalamic neurohormones have recently become apparent and clinically relevant, based on the use of synthetic peptide analogs for the treatment of multiple conditions including cancers, pulmonary edema and myocardial infarction. In the eye, it has been suggested that some of these hormones and their receptors may be present in the ciliary body, iris, trabecular meshwork and retina, but their physiological role has yet to be elucidated. Our study intends to comprehensively demonstrate the expression of some hypothalamic neuroendocrine hormones and their receptors within different retinal and extraretinal structures of the human eye. Immunofluorescence, Western blot analysis, and RT-PCR were used to evaluate the qualitative and quantitative expression of Luteinizing Hormone Releasing Hormone (LHRH), Growth Hormone Releasing Hormone (GHRH), Thyrotropin Releasing Hormone (TRH), Gastrin Releasing Peptide (GRP) and Somatostatin as well as their respective receptors (LHRH-R, GHRH-R, TRH-R, GRP-R, SST-R1) in cadaveric human eye tissue and in paraffinized human eye tissue sections. The hypothalamic hormones LHRH, GHRH, TRH, GRP and Somatostatin and their respective receptors (LHRH-R, GHRH-R, TRH-R, GRPR/BB2 and SST-R1), were expressed in the conjunctiva, cornea, trabecular meshwork, ciliary body, lens, retina, and optic nerve.

First Locally Acquired Congenital Zika Syndrome Case in the United States: Neonatal Clinical Manifestations

In the spring of 2017, a full-term infant with microcephaly was delivered in South Florida. During first trimester, the mother presented with fever, nausea, and vomiting. She reported no foreign travel for herself or her partner. The infants neurologic, ophthalmologic, neuroradiologic, and audiologic findings were highly suggestive of congenital Zika syndrome (CZS), confirmed by IgM antibodies and plaque reduction neutralization test. New observations, including peripheral temporal retinal avascularity and peripapillary retinal nerve fiber layer thinning, are presented from this first known case of non-travel-associated CZS in the United States. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e93-e98.].

Effect of prostaglandin analogs on matrix metalloproteinases and tissue inhibitor of metalloproteinases in eyelid muscle specimens

Purpose To characterize the effect of prostaglandin analogs (PAs) on tissue specific expression of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) in levator aponeurosis resections (LAR) and conjunctiva-Muller muscle resections (CMMR). Methods Specimens from LAR and CMMR of PA users and non-users were analyzed for tissue specific expression of MMP-3, MMP-7, MMP-9 and TIMP-2 using immunohistochemistry. PA use, marginal reflex distances, levator function and palpebral fissure were documented through chart review. The associations between MMP expression, PA exposure time and ocular characteristics were evaluated with a two-factor analysis of variance and multiple correlation analysis. Results We observed a tissue specific pattern of expression of MMPs and TIMP-2 in relation to PA exposure between CMMR and LAR specimens. There was increased MMP-7 and TIMP-2 expression in muscle compared to collagen and adipose tissue (P≤0.005), as well as a statistically significant difference in the relationship of MMP-3, MMP-9 and TIMP-2 levels to PA exposure in the two types of muscles (all P≤0.011). Adipose tissue had a PA-dependent reduced expression of MMP-3 (P<0.022), which was seen in both LAR and CMMR. Decreased expression of MMP-3 in collagen correlated with increased dermatochalasis (P<0.045) and steatoblepharon (P<0.018). Conclusion PA exposure may affect MMP and TIMP expression in a tissue specific manner, and decreased expression of certain MMPs in collagen correlates to increased clinical measures of prostaglandin associated periorbitopathy (PAP). Further studies with larger samples are needed to ascertain if the changes associated with PAP are due to MMP/TIMP changes or to structural changes.

Retinal pigment epithelium changes in pediatric patients with glaucoma drainage devices

Purpose Retinal changes secondary to hypotony are usually described as wrinkling or folding of the inner portion of the choroid, the retinal pigment epithelium (RPE), and the outer retinal layers in the macular area due to scleral wall collapse. We describe a new retinal finding in children with suspected hypotony after implantation of Baerveldt Glaucoma Implant (BGI). Observations Four patients in our series developed significant RPE defects after BGI implant. The RPE defects appeared as elongated white lines observed solely in the posterior pole, in no particular pattern, and seemed to be worse in infants with anterior segment dysgenesis and with collagen disorders. Conclusion and importance Children have thinner and more elastic scleral walls than adults. This characteristic may cause the inward scleral wall to collapse when the eye is hypotonic. The resulting redundancy of the retina leads to wrinkling and RPE defects characterized by hypopigmented lines predominantly in the macular area. Such findings, to our knowledge, have not been previously reported in pediatric patients.

Variations in production and oligomers content obtained under hydrothermal treatment among five fast-growing species.

In order to identify fast growing species utilizable for olygomer and monomer production, five fast growing species (Paulownia fortunei, Chamaecytisus proliferus, Arundo donax, Leucaena.diversifolia and Sesbania grandiflora) were tested. Concurrently, the biomass productivity of these species was also tested on a field scale. The biomass produc- tivity of the selected species studied ranges from 0.36 to 21.30 t ha � 1 (o.d.b.) under Mediterranean conditions for the year 1 sprouts. In addition, the hydrothermal treatment results show that the selected species could be employed as alternative raw material for the production of oligomers, leading to a high concentration of oligomers (9.4-23.4 g/L -1 at 190oC).