Temperature-sensitive tyrosinase associated with peripheral pigmentation in oculocutaneous albinism.

Several types of autosomal recessive oculocutaneous albinism (OCA) are associated with abnormal tyrosinase function and a generalized reduction in or absence of cutaneous and eye melanin. Each is thought to result from a different mutant allele at the tyrosinase locus, with the mutation producing an enzyme with little or no activity in all involved tissues. In this paper, we report a new type of OCA that results from a tyrosinase allele producing a temperature-sensitive enzyme. The proband had white hair in the warmer areas (scalp and axilla) and progressively darker hair in the cooler areas (extremities) of her body. Melanocyte and melanosome architecture were normal. Quantitative hairbulb tyrosinase (dopa oxidase) assay demonstrated a loss of activity above 35-37 degrees C. Plasma pheomelanin and urine eumelanin intermediates were reduced and correlated with hair melanin content. This is the first temperature-sensitive tyrosinase mutation to be reported in humans and is analogous to the Siamese mutation in the cat and the Himalayan mutation in the mouse.

Effect of acute-phase retinopathy of prematurity on grating acuity development in the very low birth weight infant. The Cryotherapy for Retinopathy of Prematurity Cooperative Group.

PURPOSE: To examine the development of grating acuity in four groups of eyes in the Multicenter Study of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP): eyes with no ROP; eyes with less-than-prethreshold ROP; eyes with prethreshold ROP; and eyes with threshold ROP that were randomized to serve as controls (not treated with cryotherapy). METHODS: Subjects were 1398 children with birth weights < 1251 g whose acute-phase ROP was documented as part of the CRYO-ROP study. Monocular grating acuity was measured using the Teller acuity card procedure when children reached 1, 2, 3 1/2, and 4 1/2 years of age. RESULTS: Eyes in the no-ROP and less-than-prethreshold groups showed nearly identical acuity development. Eyes with prethreshold ROP showed mean acuity similar to the no-ROP group at 1 and 2 years, but slightly below the no-ROP group at 3 1/2 and 4 1/2 years. Only 50% of eyes in the threshold untreated ROP group had measurable acuity. These eyes showed mean acuity scores that were approximately 1 octave below those of the no-ROP group at all four test ages. When data from eyes with ROP residua or other ocular abnormalities, and data from eyes of children who were unable to pass the study developmental screening items, were excluded, acuity development was similar among groups. CONCLUSIONS: Mild (less-than-prethreshold) ROP has no effect on the development of grating acuity in children between 1 and 4 1/2 years of age. Moderate (prethreshold) ROP is associated with reduced acuity at 3 1/2 and 4 1/2 years. In general, severe (threshold untreated) ROP results in moderate to severe reductions in acuity at all ages between 1 and 4 1/2 years. However, a small number of children with severe ROP show normal acuity development.

Variable expression of vision in sibs with albinism.

Oculocutaneous albinism is defined by the presence of cutaneous and ocular hypopigmentation, the latter associated with nystagmus, iris transillumination, reduced retinal pigment, foveal hypoplasia, and misrouting of the optic fibers at the chiasm. The visual acuity is variable but almost always reduced. We report on two brothers with oculocutaneous albinism and markedly different visual acuity. One brother has a visual acuity of 20/100, while the second has similar cutaneous pigmentation and visual acuity of 20/20 and had not previously been recognized as having oculocutaneous albinism. Both brothers have foveal hypoplasia and misrouting of the optic fibers at the chiasm. Biochemical analysis suggests that this is a tyrosinase-related type of oculocutaneous albinism. This study demonstrates that careful observation of foveal development in relatives with normal vision is necessary to detect all individuals with albinism in a family. A suspected diagnosis of albinism may be confirmed when the visual-evoked potentials show excessive decussation of the optic fibers at the chiasm.

Long-term outcome of Hurler syndrome following bone marrow transplantation.

Previous reports suggested a therapeutic response of lysosomal storage diseases such as Hurler syndrome following bone marrow transplantation. However, a clearer understanding of outcome has awaited long-term follow-up. We evaluated prospectively 11 consecutive patients with Hurler syndrome receiving marrow from an HLA-identical sib donor between September 1983-October 1988. Follow-up evaluations included assessment of donor engraftment by restriction fragment polymorphism analysis, determination of leukocyte alpha-L-iduronidase level, measurement of lumbar cerebrospinal fluid (CSF) pressure, computerized tomography (CT) of the brain, and psychometric testing. In this series there was a survival rate of 9/11 (82%) with all survivors showing complete (7 patients) or partial (2 patients) donor engraftment. Prospective longitudinal evaluation of the 9 surviving children, now 3.8-8.9 years posttransplantation (median 5.5) demonstrated persistence of previously deficient leukocyte alpha-L-iduronidase at levels reflecting the donor genotype and degree of donor engraftment. Urinary glycosaminoglycan excretion declined to near-normal within 5 months of donor engraftment. Prior to treatment, 7 of 8 children studied were found to have occult intracranial hypertension (lumbar CSF pressure > 20 cm CSF); however, all surviving children attained normal or near-normal pressure within 18 months of donor engraftment. Longterm follow-up CT imaging of the brain did not show progressive volume loss (cerebral atrophy) after donor engraftment. Of 9 survivors, 4 children having a developmental quotient (DQ, Mental Development Index on Bayley Scales of Infant Development) above 80 prior to transplantation subsequently maintained IQ scores above this level. However, 5 patients with lower pretransplant DQ scores now have significant cognitive deficits and attention deficit hyperactivity disorder. Progressive brain damage resulting from communicating hydrocephalus may be prevented by successful engraftment. Early transplantation of children with Hurler syndrome who have normal intelligence is likely to have the clearest benefit because long-term intellectual outcome will be limited by brain damage which has occurred prior to treatment.

High injection pressure during intralesional injection of corticosteroids into capillary hemangiomas.

BACKGROUND: Intralesional injection of corticosteroids is an effective treatment for tumors of the head and neck. Complications are rare but include permanent loss of vision. We designed a study to investigate the mechanism for this complication. METHODS: Three fellowship-trained pediatric ophthalmologists participated in the study in a nonmasked fashion. Four patients received 5 separate treatment sessions of an intralesional injection of a 50-50 mixture of triamcinolone diacetate (40 mg/mL) and betamethasone sodium phosphate and betamethasone acetate (6 mg/mL) into capillary hemangiomas. Injection pressure was obtained in real time using a cannula designed for this purpose. Maximum pressure, mean pressure, and volume of corticosteroid were measured from each injection. RESULTS: A total of 71 injections (range, 8-33 injections per patient) was performed. The total volume of corticosteroid ranged from 0.9 to 2.1 mL. In 63 of 71 injections, the maximum pressure exceeded 100 mm Hg (range, 18.65-842.18 mm Hg). Each surgeon produced injection pressures greater than the systemic arterial pressures of each patient. CONCLUSIONS: Injection pressures exceeding the systemic arterial pressures routinely occur during intralesional injections of corticosteroids into capillary hemangiomas. Experienced surgeons participating in a nonmasked protocol were unable to prevent high injection pressures of corticosteroid. A sufficient volume of corticosteroid injected at high injection pressure would account for the embolization of corticosteroid particles into the ocular circulation from retrograde arterial flow. We recommend limiting the volume of corticosteroid and performing indirect ophthalmoscopy on all patients receiving injections of long-acting corticosteroids into the orbit and periorbital soft tissue.

Surfactant prophylaxis and retinopathy of prematurity.

OBJECTIVE: The use of exogenous surfactant has led to a decrease in mortality of low-birth-weight infants. In some instances, use of this drug has also led to a reduction in neonatal morbidity, such as respiratory distress syndrome. This study was undertaken to determine whether prophylactic surfactant therapy has an effect on the incidence and severity of retinopathy of prematurity. DESIGN: The authors reviewed the findings of sequential prospective ophthalmologic examinations performed in two neonatal intensive care units that participated in randomized trials of prophylactic exogenous mammalian surfactant. PATIENTS: There were 43 patients in the control group (no prophylactic surfactant) and 43 patients in the prophylactic surfactant group. These groups did not differ on the basis of birth weight, gestational age, race, or gender. RESULTS: The incidence and severity of retinopathy of prematurity did not vary between the control and surfactant-treated infants. Only birth weight appeared to be significantly related to the incidence and severity of retinopathy of prematurity. CONCLUSIONS: These results suggest that the widespread use of prophylactic surfactant therapy will not change the incidence of retinopathy of prematurity in extremely low-birth-weight infants. However, the absolute number of affected patients will likely increase because of the decrease in mortality of extremely low-birth-weight patients, the patients most at risk for retinopathy of prematurity.

Ocular ischemic syndrome in a child with moyamoya disease and neurofibromatosis.

Ocular ischemic syndrome is extremely rare in childhood. Patients with moyamoya disease may be particularly susceptible to the development of ocular ischemia due to the associated carotid occlusion. A 19-month-old boy presented with neurofibromatosis and signs of ocular ischemia. At 29 months of age, he developed dense right vitreous hemorrhage and eventually lost vision in that eye due to phthisis. At almost six years of age, he developed an acute hemiplegia and was then diagnosed with moyamoya disease. This rare instance of childhood ocular ischemia in conjunction with moyamoya disease and neurofibromatosis demonstrates the serious ocular and systemic sequelae of occlusive vascular disease.

Vision despite tomographic absence of the occipital cortex.

A 14-month-old boy with developmental delay showed microcephaly, spastic diplegia, central visual fixation and an esotropia. A head tomographic scan disclosed absence of normal occipital cortex and electroencephalography showed markedly reduced voltages over the occipital region. Visual development in this patient may be related to heterotopic occipital cortex of a functioning non-striate system of visual processing. Visual function cannot be predicted when severe developmental anomalies of the occipital cortex are detected with computerized tomography.

Phase contrast microscopy. Diagnosis of ghost cell glaucoma following cataract extraction.

Ghost cell glaucoma may be suspected when intraocular pressure remains elevated following vitreous hemorrhage. Vitrectomy provides relief of the glaucoma and an improvement in vision. The vitrectomy specimen offers confirmation of the clinical diagnosis when examined by phase contrast microscopy.

Diagnosis of oculocutaneous albinism with molecular analysis.

PURPOSE: To use molecular analysis to diagnose oculocutaneous albinism in a patient with an atypical clinical presentation. METHODS: A 34-year-old woman with a history of strabismus and absent cutaneous pigment underwent comprehensive ophthalmic examination, visual-evoked potentials to detect altered optic decussation, and molecular analysis. RESULTS: Examination showed fine nystagmus, iris transillumination, foveal hypoplasia, and corrected visual acuity of 20/25 in each eye. Misrouting of the retinostriate fibers was demonstrated with visual-evoked potentials. Mutations in the tyrosinase gene established the diagnosis of oculocutaneous albinism 1 even though the patient had atypical clinical features. CONCLUSIONS: Molecular analysis can establish the diagnosis of oculocutaneous albinism 1 in the patient with atypical ocular features.

Juvenile iridoschisis and microphthalmos.

Spontaneous iridoschisis and corneal edema developed in the microphthalmic eye of an 8-year-old. There was no history of trauma, inflammation, or congenital iris abnormality.

Optic nerve neovascularization in incontinentia pigmenti.

PURPOSE: To describe the presence of optic disk neovascularization in a child with incontinentia pigmenti. METHODS: A 6-month-old infant with incontinentia pigmenti developed optic disk neovascularization in addition to vascular abnormalities in the peripheral retina. Panretinal photocoagulation was performed. RESULT: The optic disk neovascularization regressed after panretinal photocoagulation. CONCLUSIONS: Optic disk neovascularization is another notable retinal manifestation of incontinentia pigmenti. When optic disk neovascularization is detected, retinal ablation should be considered as treatment.

Dense peripheral corneal clouding in Scheie syndrome.

A 28-year-old woman with Scheie syndrome (MPS I-S) presented with the unusual feature of extremely dense peripheral corneal clouding, allowing maintenance of good central visual acuity. Characteristic systemic features, an abnormal electroretinogram result, and absent alpha-L-iduronidase activity confirmed the diagnosis despite the unusual corneal pattern of clouding.

Paroxysmal facial itch: a presenting sign of childhood brainstem glioma.

Two children with neurofibromatosis and a chief complaint of severe, episodic, unilateral facial itching were found to have brainstem glioma. Initial computerized tomography of the brain was thought to be normal, but the brainstem tumor was subsequently demonstrated on magnetic resonance imaging. The paroxysmal facial itching resolved in both cases after a course of radiation therapy. The pathophysiology of the attacks of facial itching is unknown but must be related to the brainstem glioma. This is the first report of paroxysmal, unilateral facial itching as a presenting sign of childhood brainstem tumor.

Albinism.

Genetic abnormalities of the melanin pigment system in which the synthesis of melanin is reduced or absent are called albinism. The reduction in melanin synthesis can involve the skin, hair follicle, and eye, resulting in oculocutaneous albinism, or can be localized primarily to the eye, resulting in ocular albinism. Approximately 1 in 17,000 individuals in the United States has oculocutaneous albinism, and more than 1 per cent of the population are heterozygous for a gene producing albinism.

Children with mucopolysaccharidosis: perioperative care, morbidity, mortality, and new findings.

The perioperative care, morbidity, and mortality in 30 patients with mucopolysaccharidosis (MPS) are presented. They underwent a detailed preoperative assessment and were anesthetized 141 times. An intravenous induction technique was used in most patients. It was easier to see the vocal cords, during laryngoscopy, in children with Hurler syndrome (HS) when they were younger (23 v 41 months, P < or = .01) and smaller (12 v 15 kg, P < or = .05). Preoperative obstructive breathing was associated with a significantly higher incidence of postextubation obstruction (P < or = .05). A total of 28 children underwent bone marrow transplantation (BMT); this reversed upper airway obstruction and also reversed intracranial hypertension. In children with HS, the incidence of odontoid dysplasia was 94%; 38% demonstrated anterior C1-C2 subluxation. Head and neck manipulation was limited in children with cervical spine defects. None of the 30 patients experienced spinal cord morbidity. One child suffered an intraoperative stroke; another, pulmonary edema. Severe and extensive coronary obstruction was responsible for 2 intraoperative deaths. Coronary angiography underestimated coronary artery disease.

Neonatal asteroid hyalosis.

Asteroid hyalosis, noted in 0.83% of routine eye examinations, is uncommon in younger patients and is more frequently seen in patients more than 60 years old. It has been considered to be related to an aging process, and when it occurs in younger patients, ocular disease is typically associated. We report a 4-week-old patient with Down syndrome and bilateral congenital cataracts who had unilateral asteroid hyalosis.

Stereopsis in patients with albinism: clinical correlates.

PURPOSE: A hallmark of albinism is excessive decussation of retinostriate projections at the optic chiasm. This misprojection might lead to abnormalities in the retinal correspondence and may account for the usual absence of stereovision. We report on 2 groups of patients with albinism who have either fine or gross stereopsis and compare the clinical findings of these groups to other patients with albinism with similar visual acuities but no stereopsis. METHODS: A retrospective chart review of patients with albinism was used to segregate those with a letter visual acuity of 20/100 or better in one eye, assessment of stereopsis, and strabismus < or = 10 PD. Forty-five patients were identified. Albinism type, best-corrected visual acuity, motility, Titmus vectograph stereoacuity, iris and macula transparency grades, and the presence or absence of both melanin and an annular reflex in the macula were tabulated. A comparison of the clinical characteristics of the groups with and without stereopsis was made. RESULTS: Those albino subjects who demonstrated stereopsis had better visual acuity, less iris transillumination, more frequent presence of melanin in the macula, less nystagmus, and less marked foveal hypoplasia than the albino subjects without stereopsis. No nystagmus was clinically detected in 5 patients with fine stereopsis. All these differences were statistically significant. Macular transparency grade was not significantly different between the groups. CONCLUSIONS: Patients with albinism who demonstrate stereopsis tend to have better visual acuity, more iris pigment, and more melanin pigment in the macula than their counterparts without stereopsis.

Change in refractive error after unilateral levator resection for congenital ptosis.

PURPOSE: To analyze refractive change in children with congenital ptosis who have undergone unilateral levator resection. METHODS: All charts of patients with congenital ptosis who underwent one levator resection performed by 2 pediatric ophthalmologists at the University of Minnesota from 1981 through 1995 were reviewed. Postoperative refractive changes were analyzed within the group of eyes that underwent ptosis repair and within the group of fellow eyes that served as age-matched controls. The preoperative and postoperative refractive error of each operated eye was also compared with its paired unoperated eye. RESULTS: Complete preoperative and postoperative refractive data were available for 28 patients with congenital ptosis requiring only one levator resection. The mean age at surgery was 3 years 8 months. The preoperative mean ptosis was 3.5 mm (range, 1.5-6 mm). At the last postoperative visit (mean, 20 months; SD, 11 months), the mean refractive change in the operated eye was 1.23 D sphere (range, 0-3.50 D; P =.061) and 0.83 D cylinder (range, 0-3.00 D; P =.002). Within the group of control eyes, no significant mean spherical or cylindrical changes were found at the last postoperative visit. Fourteen eyes with preoperative ptosis had a cylindrical change of 0.75 D or more, compared with a similar change in 4 control eyes. When refractive errors were compared interocularly, no statistically significant differences were found. CONCLUSIONS: Our results showed significant cylindrical change in eyes that underwent levator resection for unilateral congenital ptosis. Careful refraction is necessary after unilateral levator resection.

Management of corn leafhopper (Homoptera: Cicadellidae) and corn stunt disease in sweet corn using reflective mulch.

Plastic reflective mulches significantly reduced populations of corn leafhopper, Dalbulus maidis (DeLong & Wolcott), adults and the incidence of corn stunt disease caused by Spiroplasma kunkelii (CSS) in late planted sweet corn (Zea mays L.). The reflective mulches were more effective than were either foliar or soil applied insecticides in managing both the leafhopper and the pathogen it transmits. Yields of marketable ears were 1.5 to 2 times greater in reflective mulch plots than from fallow plots. This was due to larger ears (individual ear weight and length) rather than an increase in the number of ears. The use of reflective mulches provides an alternative strategy to insecticides in the management of both D. maidis and corn stunt disease. Such a strategy may prove useful to growers in Latin America and to limited resource growers and organic growers in the United States who wish to grow corn without the use of insecticides.