Floating-Harbor syndrome with chorioretinal colobomas.

BACKGROUND: We present a case of a child with Floating-Harbor Syndrome (FHS) with bilateral chorioretinal coloboma (CC). To the best of our knowledge, this is the first case report of this association. Floating- Harbor syndrome is an extremely rare autosomal dominant genetic disorder with approximately 100 cases reported. It is characterized by a series of atypical features that include short stature with delayed bone age, low birth weight, skeletal anomalies, delayed speech development, and dysmorphic facial characteristics that typically portray a triangular face, deep-set eyes, long eyelashes, and prominent nose. MATERIALS AND METHODS: Our patient was examined by a pediatric ophthalmologist for the time at age of 7. Visual acuity, optical coherence tomography (OCT) and Optos imaging were collected on every visit. The patient had whole genome sequencing ordered by a pediatric geneticist to confirm Floating-Harbor syndrome. RESULTS: We present the patient's OCT and Optos images that illustrate the location of the patient's inferior chorioretinal coloboma in both eyes. The whole genome sequencing report collected revealed a heterozygous de novo pathogenic variant in the SRCAP gene, consistent with a Floating-Harbor syndrome diagnosis in the literature. DISCUSSION: Both genetic and systemic findings are consistent with the diagnosis of Floating-Harbor syndrome in our patient. Rubenstein-Taybi and Floating-Harbor syndrome share a similarity in molecular and physical manifestations, but because of the prevalence in Rubenstein-Taybi diagnoses, it is a syndromic condition that includes coloboma and frequently associated with each other. Therefore, a retinal exam should become part of the standard protocol for those with FHS, as proper diagnosis, examination and treatment can prevent irreversible retinal damage.

Optic glioma warranting treatment in children.

PURPOSE: To describe cases of optic pathway glioma (OPG) warranting treatment in children. METHODS: This is a retrospective review of pediatric patients treated for OPG. The clinical data and imaging studies were obtained from the medical records and radiology files of patients seen at the Pediatric Neuro-Ophthalmology Clinic at the University of Illinois, Chicago and the private office of the author (LMK). RESULTS: A total of seven cases with an age range of 3-48 months at presentation were reviewed. Three of the patients were also ultimately diagnosed with neurofibromatosis type 1. Presenting symptoms included proptosis, decreased vision, gaze deficit, and nystagmus. Four patients underwent biopsies that confirmed OPG. Six of the patients were treated with intravenous chemotherapy, with three patients requiring a second chemotherapy cycle. One patient was successfully treated with an en-bloc optic nerve excision. Two patients underwent unilateral enucleation owing to globe complications. CONCLUSION: Although benign tumours, OPG can behave very aggressively in young children. Both chemotherapy and en-bloc excision can be employed for treatment.

A syndrome of retinitis pigmentosa, congenital ichthyosis, hypergonadotropic hypogonadism, small stature, mental retardation, cranial dysmorphism, and abnormal electroencephalogram.

BACKGROUND: Retinal dystrophy and ichthyosis occur together in patients with the well-characterized disorders of Refsum disease and Sjögren-Larsson syndrome. Rud syndrome formerly was considered a genetically heterogeneous but distinct clinical entity with the manifestations of icthyosis, hypogonadism, small stature, mental retardation, epilepsy, and, infrequently, retinitis pigmentosa. Although there are at least 55 case reports of Rud syndrome in the medical literature, the existence of such a syndrome has recently been dismissed based on a new understanding of the ichthyoses. Most case reports previously reported as Rud syndrome can now be reassigned under a contemporary ichthyosis classification that does not include Rud syndrome as a distinct entity. METHODS: Two unrelated women with a disorder showing retinitis pigmentosa, congenital ichthyosis, hypergonadotropic hypogonadism, small stature, mental retardation, cranial dysmorphism, and abnormal electroencephalograms underwent a comprehensive workup. The ocular and systemic findings are compared with those previously described for retinal dystrophy and ichthyosis disorders. RESULTS: These cases were found to be clearly distinct from Refsum disease, Sjögren-Larsson syndrome, and any of the other ichthyosis disorders that have been suggested as a replacement for Rud syndrome. CONCLUSION: The association of retinitis pigmentosa, congenital ichthyosis, hypergonadotropic hypogonadism, small stature, mental retardation, cranial dysmorphism, and abnormal electroencephalogram may represent a distinct syndrome previously considered a subset of the now defunct Rud syndrome.

Prevalence of myopia between 3 months and 5 1/2 years in preterm infants with and without retinopathy of prematurity. Cryotherapy for Retinopathy of Prematurity Cooperative Group.

PURPOSE: The purpose of the study was to examine spherical equivalent refractive errors, especially myopia, at six ages between 3 months and 5 1/2 years post-term in preterm children with birth weights of less than 1251 g. DESIGN: A cohort study. PARTICIPANTS: There were a total of 827 participants in the multicenter study of cryotherapy for retinopathy of prematurity (ROP). Approximately one third of the eyes did not develop ROP, whereas two thirds developed mild-to-severe ROP. None of the eyes underwent cryotherapy. INTERVENTION: Refractive error was measured at 3 months, 1 year, and 5 1/2 years term due date at the five long-term follow-up centers. In most eyes, refractive error also was measured at 2, 3 1/2, and 4 1/2 years. MAIN OUTCOME MEASURE: Myopia was defined as 0.25 diopter (D) or greater with high myopia as 5 D or greater. RESULTS: The proportion of eyes with myopia in this preterm population was increased compared to published data on full-term children and was related to severity of both acute-phase and cicatricial-phase ROP. The percentage of eyes with myopia varied little across ages, ranging from 21.2% at 1 year to 15.7% at 4 1/2 years. The percentage of eyes with high myopia doubled from 1.8% to 3.9% between 3 months and 1 year and remained stable thereafter. The distribution of refractive errors in eyes with mild acute-phase ROP was similar to that of eyes with no ROP. In contrast, eyes with moderate or severe acute-phase ROP showed an increased prevalence of high myopia. The distribution of refractive errors changed between 3 months and 1 year with little change after 1 year. This pattern of refractive development differs from that of full-term infants. Birth weight, severity of ROP, and degree of myopia at 3 months predicted the presence of myopia and high myopia at 5 1/2 years of age. CONCLUSIONS: The distribution of refractive errors in preterm infants from age 3 months to 5 1/2 years varies with severity of acute-phase ROP and cicatricial disease. Changes in refractive error distribution occur primarily between 3 months and 1 year and involve a decrease in the proportion of eyes with hyperopia and an increase in the proportion with high degrees of myopia.

Monocanalicular intubation with Monoka tubes for the treatment of congenital nasolacrimal duct obstruction.

OBJECTIVE: Nasolacrimal duct intubation with Silastic tubes often is used for the treatment of congenital nasolacrimal duct obstruction. The more established intubation technique uses tubing designed for bicanalicular intubation. A commercial product now is available for monocanalicular intubation (Monoka tube, FCI, Issy-Les-Moulineaux Cedex, France), made possible by a punctal anchor attached to the proximal end of the tubing. The authors evaluated the complications and results of their experience with Silastic tube monocanalicular intubation for treatment of congenital nasolacrimal duct obstruction. DESIGN: The study design was a retrospectively reviewed clinical trial with the results compared to a historic cohort treated with an alternative medical device. PARTICIPANTS: Thirty-nine pediatric patients with 48 obstructed congenital nasolacrimal ducts were available for treatment and postoperative follow-up. The historic cohort included 25 cases of congenital nasolacrimal duct obstruction. INTERVENTION: The participants were treated with monocanalicular Silastic tube intubation. The historic cohort was treated with bicanalicular Silastic tube intubation. The tubes were left in place for 4 to 6 months before planned removal. MAIN OUTCOME MEASURES: Dye disappearance tests were performed before and after surgery after removal of the tube. Intraoperative and postoperative complications were noted. RESULTS: Significant complications of the monocanalicular tubing included 1 case of bilateral preseptal cellulitis, 1 case of migration of the punctal anchor into the canaliculus that required surgical correction, 2 cases of a corneal abrasion, 1 case of a corneal ulcer, and 21 cases of premature removal of the tube. Of the 21 cases with premature tube removal, 13 (62%) of the eyes showed an improvement in the symptoms and results of dye disappearance test. Of the 27 cases that completed the full course of tube placement, all the tubes were removed successfully in an office setting, and 25 (93%) showed an improvement in the symptoms and results of dye disappearance test. Significant complications of the authors' bicanalicular intubation include stretching of the punctum, tube dislodgement, and tube removal requiring general anesthesia to the patient. Of the authors' 25 cases treated with bicanalicular intubation, 17 (68%) showed an improvement in the symptoms and results of dye disappearance test. CONCLUSION: The recently introduced Silastic monocanalicular tubing offers an alternative to bicanalicular tubing for treatment with intubation of congenital nasolacrimal duct obstruction. Complications due to intubation persist with the monocanalicular tube. However, some of the complications the authors encountered may be avoided by a recent change in the design of the tubing and by familiarity with recommended techniques. The overall success rate of 79% with the Monoka tube is lower than that for published reports of bicanalicular intubation.

Retinoblastoma and simulating lesions. Role of CT, MR imaging and use of Gd-DTPA contrast enhancement.

The diagnosis of Rb can usually be made by clinical examination; however, patients should also be studied by CT and MR imaging to help determine the extent of the intraocular tumor, document intralesional calcification, confirm the diagnosis, and delineate orbital or intracranial involvement. These imaging techniques should aid the clinician in differentiating Rb from lesions that simulate Rb.

Diagnostic imaging of cystic lesions in the child's orbit.

The child's orbit may be involved with a variety of cysts and cyst-like lesions. Such lesions may represent development anomalies of the globe and orbit, acquired lesions of the orbit, or cystic expansions from contiguous structures. CT and MR imaging are important diagnostic tools that aid the ophthalmologist in establishing the correct diagnosis and defining the extent of these cystic lesions.

Mitomycin in the treatment of hypertrophic conjunctival scars after strabismus surgery.

A recognized complication of strabismus surgery is the development of hypertrophic conjunctival scars over the operated-on muscle. Our standard treatment of these scars has been excision followed by corticosteroid eye drops, which results in a scar recurrence rate of 33%. Antimetabolic chemotherapeutic agents, such as mitomycin, can reduce posttraumatic scarring and vascularization of the ocular surface. We studied the use of mitomycin eye drops as an adjunct to standard treatment of hypertrophic conjunctival scars after strabismus surgery. Four patients were treated with adjunct mitomycin eye drops (0.2 to 0.4 mg/ml). Postoperative follow up ranged from 16 to 56 weeks. None of these cases showed significant scar recurrence. Mitomycin in the higher dosage caused mild superficial punctate keratitis after 8 days of use. Despite a lamellar sclerectomy in a patient treated with 0.2 mg/ml of mitomycin, there was no further clinically apparent loss of scleral tissue. The results of this pilot study suggest that topical mitomycin is a safe and effective adjunct to excision and corticosteroid eyedrops in the treatment of hypertrophic conjunctival scars after strabismus surgery.

Lupron retards proliferation of ovarian epithelial tumor cells cultured in serum-free medium.

Some patients with recurrent ovarian epithelial cancer respond favorably to treatment with GnRH agonists. This effect was proposed to be mediated by suppression of pituitary gonadotropin release. The present in vitro study investigated effects of human gonadotropin (Pergonal LH/FSH, 1:1) and Lupron, a GnRH agonist, on proliferation of an ovarian cancer cell line, 2774, which is estrogen receptor negative and grows well in serum-free, defined medium. Pergonal, 10 IU/mL or 30 IU/mL, did not enhance cell proliferation, which argues against stabilization of ovarian tumors in vivo due to decreased serum gonadotropin. Lupron, 1.4 micrograms/mL and 140 micrograms/mL, retarded cell division by day 6-8 of culture, in a dose-dependent manner. Flow cytometric cell cycle phase DNA analysis demonstrated Lupron caused a reversible 5-6% increase in the portion of cells in rest phase, G0/G1, compared to controls during log growth, and a corresponding decrease in the portion of cells in DNA synthesis, S phase. However, long-term culture, 3 weeks, with Lupron failed to arrest cells in G0/G1, and experimental cultures plateaued at cell number similar to control cultures. We conclude Lupron's effect on ovarian cancer cell proliferation is independent of gonadotropin and steroid, involves a cell cycle regulatory event, and duration of benefit observed in vivo for some patients may be related to total tumor volume at the time of treatment.

Structural and functional integrity of ovarian tumor tissue obtained by ultrasonic aspiration.

For patients with ovarian epithelial cancer, survival increases when residual disease approaches zero after surgical removal of the tumor. A previous study using the Cavitron Ultrasonic Surgical Aspirator (CUSA) (Cavitron Lasersonic Corp., Stamford, CT) showed the successful removal of ovarian tumors from areas often considered unresectable: the diaphragm, spleen, stomach, and small bowel. However, the CUSA has not yet been approved by the Food and Drug Administration for gynecologic surgery except on an experimental basis. This study was designed to test whether ultrasonic irradiation produced by the CUSA caused alterations in cell structure or physiology of gynecologic tissue in adjacent areas. Paired tumor samples, unirradiated and irradiated, were obtained from ten patients, and portions were sent for pathologic structural evaluation and physiologic tissue culture evaluation. Histologic sections, stained with hematoxylin and eosin, showed that CUSA irradiation produced only minor tissue distortion as observed under the light microscope. A correct diagnosis would have been made in all cases had only tissue fragments obtained from the CUSA specimen trap been stained. For nine of ten patients, initial tumor cell viability was similar in the two specimen types. Flow cytometric DNA analysis confirmed that surgical methods produced matched samples. Cells that survived high-frequency ultrasound appeared functionally intact. For five of eight patients, the cells from the CUSA specimen traps survived and/or divided to a greater extent than those from the knife-dissected tumors. Cells from both surgical routes attained a similar number of passages in culture. It seems reasonable to extrapolate these in vitro observations with pelvic tumor tissues to normal surrounding tissue left in situ. Thus pelvic tissue is believed to be uninjured by CUSA ultrasonic irradiation.

Respiratory epithelium in a cystic choristoma of the limbus.

A female newborn had a cystic, whitish gray mass at the inferotemporal limbus of the left eye. At age 3 weeks, the newborn underwent excision of the tumor, corneal patch grafting, and superior sector optical iridectomy. Histopathologic and electron microscopic examination of the excised tissue revealed a choristoma consisting of cysts lined with respiratory epithelium. To our knowledge, respiratory epithelium in a limbal choristoma has not been previously reported.

Invasive sinonasal polyps causing ophthalmoplegia, exophthalmos, and visual field loss.

In a 20-year-old man with a history of sinonasal polyps, bilateral ophthalmoplegia, exophthalmos, and optic nerve dysfunction developed. Radiologic imaging showed a polypoid mass filling the nose and sinuses, eroding into the pituitary fossa, basal cisterns, and orbits, and compressing the cavernous sinuses. Six months after bilateral maxillary, ethmoid, and sphenoid exploration, ocular motility returned to normal, but there remained mild generalized visual field loss in the right eye. The pathologic specimen showed polypoid respiratory mucosa with acute and chronic inflammation as well as eosinophiles.

Magnetic resonance imaging of pituitary stalk hypoplasia. A discrete midline anomaly associated with endocrine abnormalities in septo-optic dysplasia.

Septo-optic dysplasia describes optic nerve hypoplasia in association with endocrine disturbances and/or midline brain malformations. Magnetic resonance imaging of the brain was used to study two patients with optic nerve hypoplasia, endocrine abnormalities, and normal midline brain anatomy on prior computed tomographic scan. The magnetic resonance imaging scans showed normal midline brain anatomy except for failure to visualize the pituitary stalk, a structure that magnetic resonance imaging has shown to be 100% sensitive in imaging in our normal controls. We propose that our two patients have endocrine abnormalities due to the discrete anomaly of pituitary stalk hypoplasia.

Necrotizing scleritis following strabismus surgery for thyroid ophthalmopathy.

Necrotizing scleritis with inflammation of the right eye developed after bilateral eye muscle surgery for thyroid ophthalmopathy. Debilitating pain, delay in onset, and involvement of the sclera distinguish this condition from anterior segment ischemia. The surgery may have acted as a nonspecific trigger in an eye at risk for scleritis. Necrotizing scleritis has occurred infrequently after other types of eye surgery but, to our knowledge, has not been previously reported as a complication of eye muscle surgery.

Modification of an ophthalmic laser for use in sedated, reclining children.

The headrest of a neodymium-YAG ophthalmic laser was modified to accept a reclining patient. Laser procedures were then performed on children who were resting in a lateral decubitus position on a stretcher before the laser. Very little manipulation or stimulation of the children was required, and so the procedures could be done using intravenous sedation or ketamine hydrochloride without endotracheal intubation. The modified headrest can increase the indications for laser surgery in uncooperative children by making the procedure less troublesome.

Aromatization of testosterone by epithelial tumor cells cultured from patients with ovarian carcinoma.

Ovarian epithelial carcinoma originates from the surface mesothelium. It is controversial whether these tumors possess steroidogenic enzymes, similar to malignancies of other ovarian cell types. This study reports aromatase enzymatic activity for three epithelial cell lines, OV1225, OV166, and 2774, established from patients with ovarian adenocarcinoma. Aneuploidy of the cells was demonstrated by flow cytometric DNA analyses which showed OV1225 tetraploid, OV166 near diploid, and 2774 triploid. Estrogen synthesis was confirmed by measurement of estradiol (6 to 11 pg/10(7) cells/24 h) by radioimmunoassay in extracts of conditioned medium. To directly assay aromatase enzymatic activity, intact cells were incubated with tritiated testosterone. Medium was extracted with organic solvent after addition of trace 14C-labeled 17 beta-estradiol and 14C-labeled estrone. Androgen was separated from estrogen by celite column chromatography. Estrogen was further purified by silica gel thin-layer chromatography and derivatization of separate products to acetates. Purity of compounds was confirmed by consistency of the 3H:14C ratio of acetylated product versus that of product recrystallized with authentic standard. Conversion of testosterone to estradiol proceeded with apparent Michaelis-Menten kinetics. The apparent Km was 4 microM, 15 microM, and 59 microM, and the Vmax was 20 pmol/h/mg of cell protein, 52 pmol/h/mg of cell protein, and 152 pmol/h/mg of cell protein for 2774, OV166, and OV1225, respectively. We conclude that at least a portion of ovarian adenocarcinoma possesses sufficient aromatase activity to convert ovarian stromal androgen to estrogen.

Characterization of tissue-derived macromolecules affecting transmitter synthesis in rat spinal cord neurons.

Rat spinal cord cells maintained in neuron-rich cultures were exposed to extracts of skeletal muscle or to medium conditioned by non-neuronal cells. The conditioned media enhanced neuronal acetylcholine (ACh) synthesis, choline acetyltransferase activity, and protein synthesis, and decreased gamma-aminobutyric acid (GABA) synthesis. Muscle extract prepared from newborn rats produced similar enhancements but did not depress GABA synthesis. Muscle extracts prepared from normal and denervated adult rat limbs contained relatively little activity. These results suggest that different molecular factors might mediate the effects on GABA and ACh synthesis. Gel filtration of conditioned media and muscle extracts revealed that all of these activities were confined to a macromolecular fraction with an apparent Mr of 40,000. These tissue-derived factors affecting neuronal protein and transmitter synthesis are in turn distinct from a neuronal survival-promoting factor obtained from serum (Kaufman, L. M., and J. N. Barrett (1983) Science 220: 1394-1396).

Serum factor supporting long-term survival of rat central neurons in culture.

Gel filtration of serum at pH 3.6 yielded a fraction that supported long-term (months) survival of dissociated rat central neurons in monolayer culture more reliably than the traditionally used unfractionated serum. The cultures remained neuron-rich, because this fraction did not support the proliferation of glia and fibroblasts that occurs in whole serum. With an apparent molecular weight of 55,000 and an isoelectric point of 5.6, the active factor (or factors) in this fraction is distinct from any well-defined growth factor.