Thinning of the Skull Base and Calvarial Thickness in Patients With Idiopathic Intracranial Hypertension.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a disorder characterized by elevated intracranial pressure without secondary causes on neuroimaging. IIH typically occurs in young, obese female patients and, when severe, can cause permanent and irreversible vision loss. The association between skull base thinning in patients with intracranial hypertension and obesity has been previously reported; however, no study has reported these findings in IIH. The goal of our study is to determine whether IIH is independently associated with skull base and calvarial thinning. METHODS: A retrospective, matched case-control study was performed. Each patient diagnosed with IIH (case) was matched with a patient diagnosed with headache (control) by age, gender, and race. Patients were included if they underwent computed tomographic imaging of the head, maxillofacial, or orbits within 3 months of their diagnosis. Exclusion criteria were history of skull base or frontal bone pathology because of surgery or skull trauma, central nervous system infections, or incomplete radiologic data. Patient demographics, medical history, clinical examination, and skull base, calvarial, and zygoma thickness were recorded. Skull base thickness was measured by the height of the auditory canal in the coronal plane. Calvarial thickness was measured just anterior to the foramen rotundum in the coronal plane. Extracranial zygoma thickness was measured and used as an internal imaging control because the zygoma is not subject to intracranial forces. RESULTS: One hundred twenty-six patients were included in the study, 63 cases and 63 controls. Each group comprised 61 female patients (97%), 24 (38%) Caucasian, 23 (37%) black, 1 (2%) Asian, and 15 (24%) others. The average age was 31.5 ± 8.7 years. Patients with IIH were more likely to be obese (n = 60, 95%) compared with the control patients (n = 23, 37%, P < 0.001). All patients with IIH underwent lumbar puncture (LP) with an average opening pressure (OP) of 40.5 ± 15.6 cm H2O, whereas only 13 (20%) controls underwent an LP with a mean OP of 19.5 ± 8.5 cm H2O. There was no statistical difference in mean visual acuity between the IIH and control groups (logMar 0.22 [20/30] ± 0.45 vs logMar 0.09 [20/25] ± 0.30, P = 0.093, respectively). Compared with the controls, patients with IIH were more likely to have headache (97% vs 74%, P = 0.001), pulsatile tinnitus (48% vs 7%, P < 0.001), horizontal binocular diplopia (24% vs 4%, P = 0.006), confrontational visual field deficit (23% vs 2%, P = 0.003), and papilledema (74% vs 0%, P < 0.001). Patients with IIH had thinner skull base and calvarium width compared with the controls (mean skull base thickness 4.17 ± 0.94 mm vs 5.05 ± 1.12 mm, P < 0.001 and mean calvarial width 1.50 ± 0.50 mm vs 1.71 ± 0.61 mm, P = 0.024). Zygoma thickness was similar in both groups (mean zygoma thickness 1.18 ± 0.30 mm in the IIH group vs 1.26 ± 0.35 mm in the control group, P = 0.105). In a subgroup analysis controlling for obesity (body mass index >30 kg/m2), there was no statistically significant difference in skull base, calvarial, or zygoma thickness between obese and nonobese patients. CONCLUSIONS: Patients with IIH have thinner mean skull base and calvarial thickness compared with the controls. There was no difference in the mean extracranial zygoma thickness, which was the internal imaging control. Contrary to previous reports, we did not find an association between obesity and skull base or calvarial thinning. These findings suggest that IIH is associated with skull base and calvarial thinning.

A Unique Radiologic Case of Optic Nerve Infarction in a Patient With Mucormycosis.

ABSTRACT: This is a rare presentation of a unilateral optic nerve infarction of the left eye caused by mucormycosis in a 51-year-old man with poorly controlled Type 2 diabetes. Diffusion-weighted MRI of the orbit demonstrated extensive infarction of the left optic nerve with ipsilateral cavernous sinus thrombosis and periorbital adnexal inflammation. Left orbital exenteration and sinus debridement were performed, and mucormycosis involving the optic nerve sheath was confirmed on histopathology.

Simultaneous Orbital and Intracranial Abscesses in 17 Cases.

PURPOSE: To describe the demographics, clinical presentation, treatment, and outcomes of a rare cohort with simultaneous orbital and intracranial abscesses. METHODS: A historical cohort study of 17 patients with simultaneous orbital and intracranial abscesses between 2010 and 2018 was performed. The demographics, location of abscesses, treatment, and outcomes of these patients were analyzed. RESULTS: The mean age was 26.9 years (range 5-83 years). Fourteen patients (82%) were male. In this cohort, the most common orbital abscess location was the superior orbit, involved in 14 patients (82%). The most common site of intracranial abscess was the frontal lobe, involved in 16 patients (94%). Concurrent sinus disease was present in 16 patients (94%). Surgical evacuation was the standard of treatment, with 94% of patients undergoing at least one surgical procedure. Streptococcus species were the most common, isolated from 6 sinus cultures (43%), 3 orbitotomy cultures (21%), and 4 craniectomy cultures (36%). Staphylococcus species were also common. Most patients (94%) had stable or improved mental status and visual function at the conclusion of their treatment. CONCLUSIONS: Simultaneous orbital and intracranial abscesses are rare. Local invasion from the orbit into the intracranial space may occur from direct spread, thus superior orbital abscesses pose the greatest risk for intracranial spread. Additional factors such as infection with Streptococcus and Staphylococcus species as well as male sex appear to be risk factors for intracranial spread. For those who develop intracranial abscesses, young age and absence of seizures or altered mental status at presentation may be associated with favorable outcomes.

A Unique Presentation of Levamisole-Induced Antineutrophil- Cytoplasmic-Antibody-Positive Vasculitis Presenting as Inflammatory Orbitopathy.

A 35-year-old woman with a history of cocaine abuse presented with progressively worsening OS pain. Neuroimaging revealed a 3-cm ill-defined left orbital lesion involving the intraconal and extraconal spaces. The orbital mass was biopsied via an anterior orbitotomy approach. Pathology demonstrated prominent angiocentric granulomatous and lymphoplasmacytic inflammation consistent with vasculitis. Laboratory tests were significant for neutropenia, positive perinuclear antineutrophil cytoplasmic antibodies with high titer, and positive myeloperoxidase antibodies, consistent with levamisole-induced vasculitis. To the authors' knowledge, this is the first reported case of cocaine-levamisole-induced vasculitis presenting as orbitopathy.

Visual Outcomes of Patients With Retrobulbar Hemorrhage Undergoing Lateral Canthotomy and Cantholysis.

PURPOSE: Evaluate visual outcomes in relation to time from injury to intervention in patients who undergo lateral canthotomy with cantholysis (LCC) for retrobulbar hemorrhage (RBH). METHODS: Retrospective study of patients with orbital compartment syndrome (OCS) secondary to RBH who underwent LCC. OCS due to RBH was defined by a combination of decreased vision, proptosis, resistance to retropulsion, increased intraocular pressure, and relative afferent pupillary defect. Time from injury to intervention and change in visual acuity were calculated, with regression analysis identifying predictors of vision recovery. RESULTS: Fifteen participants were included. Three (20%) participants presented with no light perception, 7 (47%) with count fingers (CF) to light perception, and 5 (33%) with better than count fingers vision. All 5 participants who had LCC within 3 hours (twice the standard 90 minutes) gained some vision, and 6 of 10 participants who had LCC after 3 hours recovered some vision. The latest intervention with visual acuity improvement was performed 9 hours postinjury. Of 3 participants who presented with no light perception vision, 1 regained vision to 20/40 (intervention 1.7 hours postinjury), and 2 did not regain any vision (interventions at 5 and 8.7 hours postinjury). Duration from injury to intervention was associated with decreased amount of vision recovery (P = 0.03). CONCLUSIONS: Increased time to intervention with LCC was associated with less vision recovery after OCS from RBH. However, over half of participants with intervention more than 90 minutes after injury still showed visual acuity improvement. The authors recommend LCC in all patients who present with OCS regardless of the time since injury.Patients with orbital compartment syndrome may see visual recovery after lateral canthotomy and cantholysis, even if performed outside of the previously accepted 3-hour window.

Screening Criteria for Detecting Severe Ocular Injuries in the Setting of Orbital Fractures.

PURPOSE: Define incidence of severe ocular trauma in orbital fracture patients and determine if ocular signs and symptoms are useful predictors of severe ocular injuries. METHODS: Retrospective chart review was performed on all patients with orbital fractures between April 1, 2013, and December 31, 2014. Patients were included if they had radiographic evidence of acute fracture of at least one orbital wall and were evaluated by the Ophthalmology service. Demographics, concurrent injury data, and symptoms and signs of ocular trauma were collected. Concurrent ocular injuries were grouped by severity. Predictive signs or symptoms for severe ocular trauma were identified by stepwise logistic regression analysis. The threshold point for predictive signs and symptoms was detected by a receiver operating characteristic (ROC). RESULTS: Five-hundred-twelve patients were included. The most common mechanisms of injury were assault (39%), fall (25%), and motor vehicle accident (21%). The incidence of any concurrent ocular trauma was 75% (383/512), with 14% (70/512) being severe. Four signs and symptoms were predictors of severity: blurred vision (P < 0.0001), pain with eye movements (P < 0.0001), visual acuity worse than 20/40 in the ipsilateral eye (P < 0.001), and restricted motility (P < 0.001). The presence of 2 or more of these signs or symptoms was predictive of severe ocular trauma with high sensitivity (91%) and specificity (86%). CONCLUSIONS: In cooperative patients with acute orbital wall fractures, the presence of 2 or more signs or symptoms is predictive of severe ocular trauma and necessitates the need for urgent ophthalmic consultation.Severe ocular injury associated with orbital wall fracture is more likely in patients with 2 or more ophthalmic signs or symptoms.

Immune Checkpoint Inhibitors for Treatment of Metastatic Melanoma of the Orbit and Ocular Adnexa.

Programmed cell death 1 (PD-1) inhibitors are members of a new class of drugs known as immune checkpoint inhibitors and have proven efficacy in the treatment of metastatic melanoma. Herein, the authors report the use of nivolumab and pembrolizumab, 2 recently Food and Drug Administration-approved PD-1 inhibitors, in 3 patients: 1 with metastatic conjunctival melanoma and 2 with metastatic cutaneous melanoma and orbital involvement. The patients' metastatic disease responded well to drug treatment. As of this writing, 2 patients have completed therapy and remain disease free at least 1 year after treatment completion; the other patient is still receiving treatment, and his orbital disease is responding. The authors herein describe the use of PD-1 inhibitors as a new alternative in the treatment of metastatic melanoma to the orbit or metastatic ocular adnexal melanomas in these clinical settings.

Evisceration in patients with Sturge-Weber syndrome.

The management of blind, painful eyes in Sturge-Weber syndrome patients poses unique challenges to the oculoplastic surgeon. Intraocular and orbital vascular malformations and calcification may theoretically lead to unexpected hemorrhage and difficulty placing an implant in a calcified scleral shell. We present two cases of patients with Sturge-Weber syndrome with blind, painful eyes who underwent evisceration with silicone implant and discuss the relevant current literature. Both of our patients had uncomplicated surgeries and post-operative courses. Our literature review reveals that both evisceration and enucleation are viable surgical options for globe removal in Sturge-Weber syndrome, yet careful preoperative planning must be undertaken to minimize risk.

Diode Laser-Assisted Endocanalicular Dacryocystorhinostomy: A Prospective Study.

PURPOSE: To evaluate the efficacy of the diode laser in endocanalicular dacryocystorhinostomy. METHODS: A prospective, noncomparative, interventional case series using the diode laser for endocanalicular dacryocystorhinostomy in patients with tearing and nasolacrimal duct obstruction. Outcome measures included subjective tearing complaints and objective patency of the nasolacrimal system. Success was defined as improvement of symptoms with patency of nasolacrimal drainage. Patients were followed for 12 months. Institutional review board approval was obtained. RESULTS: Forty eyes (28 unilateral, 6 bilateral) underwent surgery. Five cases were excluded because of inadequate follow-up. Patients ranged in age from 27 to 88 years (66.7 ± 15.7). Seventy-seven percent were female and 23% were male. At 1 week, 88% had improvement in tearing, 12% had no change or worsening of symptoms, and all patients were patent on irrigation. At 1 month, 86% had improvement, 14% had no change, and all patients were patent on irrigation. At 3 months, 83% had improvement and were patent on irrigation. Seventeen percent had no change or worsening with reflux and were considered failures. At 6 months, 77% had improvement and were patent on irrigation. Five additional patients had no change, reflux on exam and were failed surgeries. At 12 months, 74% had complete resolution and were patent. One additional patient failed. Nine surgeries in 35 cases were considered failures by 12 months. CONCLUSIONS: Subjective complaints of tearing correlated with patency of the nasolacrimal system after 3 months. A success rate of 74.3% (26 out of 35 cases) was observed by 12 months.

Erdheim-Chester disease with orbital involvement: Case report and ophthalmic literature review.

Erdheim-Chester disease (ECD) is a rare xanthogranulomatous disease in which orbital involvement can have devastating outcomes. Through a case report and review of the ophthalmic literature, we explore orbital findings, disease progression, and treatment options. Cases of orbital involvement in Erdheim-Chester disease were identified in the ophthalmic literature with a PubMed query and review of cited references. A total of 14 publications reporting 19 separate cases that included ophthalmic examination data were identified. Patient ages ranged from 26-77 years with a mean age of 50 years. Seventy-four percent (14/19) were men. Vision progression to no light perception was found in 32% (6/19) of the patients. Reviewed cases reported a variety of medical and surgical treatment approaches, however, only 53% reported cases (10/19) demonstrated disease improvement or stabilization. Erdheim-Chester disease with orbital involvement is a devastating disease with a poor prognosis. Awareness of this entity by the ophthalmologist is important as orbital signs and symptoms may manifest early, and orbital biopsy is often crucial to the definitive diagnosis.

Non-traumatic open globe injuries: presenting characteristics and visual outcomes.

PURPOSE: To describe clinical characteristics and visual outcomes of non-traumatic open globe injuries. SETTING: A level 1 trauma centre in a large urban medical centre. DESIGN: Retrospective study. METHODS: Charts of non-traumatic open globe patients admitted to MHH-TMC from 1/2010 to 3/2015 were reviewed for demographics, cause, clinical characteristics, visual acuity (VA) and enucleation. RESULTS: Thirty eyes were included: 15 (50%) were males with a mean age of 47 (±28) years. All presented with zone 1 injury. Twenty-five (83%) had a perforated corneal ulcer. Presenting VA was count fingers (n = 3, 10%) to NLP (n = 6, 20%). Twenty-four (80%) involved infection, 5 (17%) congenital, 3 (10%) chemical burn and 2 (7%) neurotrophic. Conjunctival injection (n = 22, 77%), corneal opacification (n = 20, 71%) and relative afferent pupillary defect (n = 9, 44%) were common. After treatment, 23 (88%) were worse than 6/60 (20/200), 9 (35%) were NLP and 8 (27%) required enucleation. CONCLUSIONS: Often non-traumatic open globe injuries are zone 1 and due to perforated infectious ulcers. Compared to previously reported traumatic injuries, these have higher rates of enucleation (27% vs 8%) and poorer final VA (88% vs 68% worse than 6/60 20/200).

Orbital apex syndrome from bacterial sinusitis without orbital cellulitis.

PURPOSE: To describe a case of orbital apex syndrome as a result of isolated bacterial sinusitis. OBSERVATIONS: A 63-year-old woman presented with an orbital apex syndrome from isolated bacterial sinusitis with rapidly declining visual acuity to no light perception. We compared our case with 6 similar cases of severe vision loss from isolated bacterial sinusitis. In contrast to previously published cases, our patient presented with good vision yet deteriorated to no light perception despite appropriate treatment. CONCLUSIONS AND IMPORTANCE: Orbital apex syndrome can present as a constellation of cranial neuropathies including optic neuropathy from conditions affecting the orbital apex. Although vision loss remained permanent, prompt initiation of broad-spectrum antibiotics and antifungals and surgical intervention prevented further extension of infection into intracranial structures.

Genetic origin and proportion of basal plate surface-lining cells in normal and abnormal pregnancies.

The human placenta is a transient organ, the villous surface of which is in direct contact with the maternal circulation during pregnancy. Thus, the syncytiotrophoblast and the basal plate-lining cells are considered continuous with the endothelial layer of the maternal vasculature. Two types of cells are found on the surface of the basal plate: trophoblasts (of fetal origin) and endothelial cells of putative maternal origin. Histologic abnormalities have been described in the basal plate of the placenta obtained from patients with preeclampsia and intrauterine growth restriction. Moreover, endothelial cell dysfunction and intravascular inflammation are key features of preeclampsia. The objectives of this study were to: (1) determine the origin of the endothelial cells located in the basal plate surface of the placenta (from male fetuses); and (2) analyze the relative proportion of the intervillous surface of the basal plate occupied by trophoblasts and endothelial cells. Immunohistochemistry and morphometry were performed in placentas from women in the following clinical groups: (1) normal-term pregnancies (n = 15); (2) severe preeclampsia at term (n = 15); (3) small-for-gestational-age (SGA) neonates delivered at term (n = 15); (4) preterm deliveries (<37 weeks) without inflammation (n = 5); and (5) preterm preeclampsia (n = 5). Laser capture microdissection and polymerase chain reaction were used to determine the allelic pattern of the amelogenin gene of the endothelial cells on the intervillous surface of the basal plate. Our results showed that: (1) the endothelial cells lining the basal plate in placentas of male fetuses were uniformly of maternal origin; and (2) in placentas from uncomplicated pregnancies, the median proportion of trophoblasts and endothelial cells covering the surface of the basal plate were 27.7% and 46.5%, respectively. The remaining area of the intervillous surface of the basal plate was composed of fibrin and anchoring villi. Of interest, placentas from women who delivered an SGA neonate had a higher proportion of trophoblasts and a lower proportion of endothelial cells lining the basal plate than those from normal pregnancies (P < .05). The same tendency was observed in placentas from patients with preeclampsia. This study demonstrates that endothelial cells of maternal origin cover the intervillous surface of the basal plate of the placenta, along with trophoblasts of fetal origin. The proportion of this surface lined by trophoblasts is greater in placentas from SGA and preeclampsia than in normal pregnancy. We propose that this change reflects a compensatory mechanism whereby the basal plate surface covered by injured endothelial cells is replaced by trophoblasts or results from a failure of trophoblastic involution in abnormal pregnancies. Our observations also suggest that the lining of the basal plate can provide information about the pathology of endothelial cells in complications of pregnancy.

Human beta-defensin-2: a natural antimicrobial peptide present in amniotic fluid participates in the host response to microbial invasion of the amniotic cavity.

OBJECTIVE: Human beta-defensin-2 (HBD-2) is a potent antimicrobial peptide that is part of the innate immune response. The purpose of this study was to determine whether HBD-2 is present in amniotic fluid and if its concentration changes with microbial invasion of the amniotic cavity (MIAC) and labor. STUDY DESIGN: Amniotic fluid was retrieved by amniocentesis from 318 patients in the following groups: (1) mid-trimester (n=75); (2) term not in labor (n=28) and in labor (n=51); (3) preterm labor and intact membranes without MIAC who delivered at term (n=36), who delivered preterm without MIAC (n=52), and preterm labor with MIAC who delivered preterm (n=25); and (4) preterm premature rupture of membranes (preterm PROM) with (n=25) and without MIAC (n=26). MIAC was defined as a positive amniotic fluid culture for microorganisms. Amniotic fluid HBD-2 concentrations were determined using a sensitive and specific ELISA. Non-parametric statistics were used for analysis. RESULTS: (1) HBD-2 was detected in all amniotic fluid samples; (2) the concentration of HBD-2 did not change with gestational age from mid-trimester to term (p=0.8); (3) intra-amniotic infection was associated with a significant increase in amniotic fluid concentrations of HBD-2 in both women with preterm labor and intact membranes, and women with preterm PROM (p<0.05 for each comparison); (4) patients with preterm labor and a negative amniotic fluid culture who delivered preterm had a higher median amniotic fluid HBD-2 concentration than those with preterm labor who delivered at term (p=0.001); and (5) among patients with preterm labor without MIAC, those who had intra-amniotic inflammation (amniotic fluid white blood cell count>100 cells per mL) had a higher median amniotic fluid concentration of HBD-2 than those without this condition (p<0.002). CONCLUSION: (1) Amniotic fluid contains HBD-2, a natural antimicrobial peptide, and this may account for some of the antimicrobial activity of amniotic fluid; (2) amniotic fluid HBD-2 concentrations are increased in women with MIAC, regardless of the membrane status (intact membranes or PROM); and (3) we propose that amniotic fluid HBD-2 is part of the innate immune system within the amniotic cavity.

Fetal macrophages are not present in the myometrium of women with labor at term.

OBJECTIVE: The basic mechanisms responsible for human parturition remain to be elucidated. The influx of fetal leukocytes into the myometrium has been recently proposed to be a crucial event in the onset of murine parturition. Surfactant protein-A has been implicated in the initiation of labor. In mice, it is thought that surfactant protein-A induces migration and subsequent activation of amniotic fluid macrophages of fetal origin, which then invades the myometrium. The present study was conducted to determine whether fetal macrophages invade the myometrium of women in labor. STUDY DESIGN: Placental bed biopsy specimens were obtained from patients in labor who delivered male neonates at term (n = 7). Myometrial sections of postpartum hysterectomy specimens obtained from women who delivered of male neonates (n = 3) were also analyzed. Formalin-fixed, paraffin-embedded sections were immunostained for CD68 or CD14 (which are markers for macrophages); immunoreactive myometrial macrophages were specifically procured by laser capture microdissection. Sex typing was done by polymerase chain reaction for the amelogenin gene with genomic DNA that was isolated from the macrophages. Chromogenic in situ hybridization with a Y chromosome-specific probe was also performed on paraffin-embedded histologic sections. RESULTS: Amelogenin allelotypes of the macrophages were consistent with female alleles in all cases that were tested, indicating a maternal origin. Chromogenic in situ hybridization demonstrated the absence of Y chromosome-positive mononuclear cells in the myometrium in all cases. CONCLUSION: These observations, from a limited number of cases, suggest that migration of fetal macrophages from the amniotic cavity or the chorioamniotic membranes into the myometrium does not occur during human labor. The trafficking of fetal macrophages in labor seems to be different in humans and mice.

A rapid MMP-8 bedside test for the detection of intra-amniotic inflammation identifies patients at risk for imminent preterm delivery.

OBJECTIVE: Matrix metalloproteinase-8 (MMP-8) is an enzyme that is released during neutrophil activation. MMP-8 amniotic fluid concentrations are elevated not only in patients with intra-amniotic infection, but also in patients with negative amniotic fluid cultures who deliver preterm neonates. The objective of this study was to determine whether the results of a rapid MMP-8 bedside test predict imminent preterm delivery. This test can be performed in 15 minutes and without laboratory equipment. STUDY DESIGN: Amniotic fluid was retrieved from 331 patients admitted with increased preterm uterine contractions and intact membranes who met the inclusion criteria. Amniotic fluid was processed for microbial cultures, Gram stain, glucose concentration, and white blood cell count. Amniotic fluid samples were stored, and the MMP-8 rapid test was performed after delivery. End points included spontaneous preterm delivery within 48 hours, 7 days, and 14 days. Diagnostic indices, predictive values, and likelihood ratios were calculated. RESULTS: The prevalence of spontaneous preterm delivery within 48 hours, 7 days, and 14 days was 11.6% (38/327), 20.2% (66/327), and 24.5% (80/327), respectively (4 patients with augmentation of labor were excluded). A positive MMP-8 rapid test had a positive predictive value of 70% (23/33) for the identification of patients who delivered spontaneously within 48 hours, and 94% (31/33) for patients who were delivered within 7 days and 14 days (likelihood ratios: 17.5 [95% CI, 9-33.9], 61.3 [95% CI, 15.1-250], and 50 [95% CI, 12-196], respectively). CONCLUSION: The MMP-8 rapid test can identify patients at risk for preterm delivery within 7 days and 14 days. Moreover, a positive MMP-8 rapid test result can identify patients with intra-amniotic infection/inflammation with a high sensitivity and specificity. This rapid test will give clinicians a fast and accurate assessment of the inflammatory status of the amniotic cavity and allow for better identification of patients at risk for impending preterm delivery.

A role of the anti-angiogenic factor sVEGFR-1 in the 'mirror syndrome' (Ballantyne's syndrome).

BACKGROUND: 'Mirror syndrome' (Ballantyne's syndrome) refers to the association of fetal hydrops with placentomegaly and severe maternal edema. Preeclampsia occurs in approximately 50% of these cases. Soluble vascular endothelial growth factor receptor-1 (sVEGFR-1), an anti-angiogenic factor, has been implicated in the pathophysiology of preeclampsia (PE). OBJECTIVE: The objective of this study was to determine if the maternal plasma concentration of sVEGFR-1 is elevated in patients with mirror syndrome. STUDY DESIGN: This case-control study included patients with uncomplicated pregnancies (n = 40) and those with mirror syndrome (n = 4) matched for gestational age. Mirror syndrome was defined as fetal hydrops and severe maternal edema. Maternal plasma sVEGFR-1 concentrations were determined using specific enzyme-linked immunosorbent assays. Immunohistochemistry of sVEGFR-1 on villous trophoblasts was also performed in samples from one patient with mirror syndrome and compared with those from a patient with spontaneous preterm delivery matched for gestational age. Non-parametric statistics were used for analysis (p < 0.05). RESULTS: (1) The median maternal plasma concentration of sVEGFR-1 was significantly higher in patients with mirror syndrome than in the control group (median: 3974 pg/mL, range: 3083-10 780 vs. median: 824 pg/mL, range: 260-4712, respectively; p < 0.001). (2) All patients with mirror syndrome had sVEGFR-1 concentrations above the 95th percentile for gestational age. Syncytiotrophoblast, especially syncytial knots, showed strong staining with antibodies against sVEGFR-1 in placental samples from the patient with mirror syndrome, but not in those from the patient with spontaneous preterm delivery. CONCLUSION: High maternal plasma concentrations of sVEGFR-1 were observed in mirror syndrome. We propose that this anti-angiogenic factor may participate in the pathophysiology of this syndrome. Thus, maternal plasma determination of sVEGFR-1 may help to identify the hydropic fetus that places the mother at risk for preeclampsia.

Tissue microarray: an effective high-throughput method to study the placenta for clinical and research purposes.

OBJECTIVE: Tissue microarray (TMA) technology allows simultaneous examination of the expression of many molecular markers (protein, mRNA, DNA, etc.) with high-throughput. The application of this technology, to date, has been largely confined to the study of cancer. Placental pathology poses unique challenges because of the size of the organ, its complex anatomy, as well as its histological heterogeneity. The objective of this study was to assess the feasibility and efficiency of TMAs for immunohistochemistry and in situ hybridization of placental tissues. STUDY DESIGN: TMAs were constructed using an automated tissue arrayer. Standard 0.6-mm or 1-mm microarray needles were used. Villous parenchyma, basal plate, and chorioamniotic membranes were targeted in each block. Five mum-thick TMA sections underwent immunohistochemical analysis of both cytoplasmic and nuclear antigens using a panel of antibodies against a variety of cytoplasmic [cytokeratin-7, vascular endothelial growth factor (VEGF), and protein Z], membranous (endoglin), and nuclear (c-fos and c-jun) antigens. mRNA in situ hybridization for surfactant protein A (SP-A) and chromogenic in situ hybridization for the Y chromosome (DYZ1) were also performed. RESULTS: Validation of TMA immunoreactivity demonstrated comparable results with corresponding whole sections. When a two-tiered scoring system (positive/negative) was employed, there was agreement between two and three cores and whole tissue sections (kappa>0.7). When a three-tiered scoring system (negative, weak-positive, or strong-positive) was used, the data from three cores showed the highest agreement with whole tissue sections (kappa >0.7). In situ hybridization experiments for mRNA and DNA were also successful in that the signals were readily detectable. Successful transfer from the donor block to the recipient block differed according to the anatomical compartment. The transfer efficiency of villous parenchyma, basal plate, and chorioamniotic membranes were 96.9% (875/903), 76.7% (115/150), and 75.4% (224/297), respectively. CONCLUSION: TMA is a practical and effective tool for high-throughput molecular analysis of the human placenta. Duplicate and triplicate cores offer agreement with whole tissue sections for two-category distinction immunostaining. TMA also affords relevant results from in situ hybridization experiments for mRNA and DNA. The major advantages are the conservation of tissues and reagents, simultaneous comparison of molecular markers in different anatomical compartments of the placenta, and reduction of experimental error.

Complete Vision Loss following Orbital Cellulitis Secondary to Acute Dacryocystitis.

We present a case of a 50-year-old woman with acute dacryocystitis that was complicated by posterior rupture of the lacrimal sac causing an orbital cellulitis with subsequent visual acuity of no light perception. Upon presentation, she was immediately started on broad-spectrum antibiotics and underwent surgical incision and drainage of the lacrimal sac abscess but never regained vision. There are 4 cases in the literature of permanent severe vision loss from acute dacryocystitis. Prompt diagnosis and close monitoring of acute dacryocystitis are therefore essential to prevent extension into the orbit and possible optic nerve compromise.