A maculopathy associated with the 15257 mitochondrial DNA mutation.

OBJECTIVE: To report a new retinal finding associated with the mitochondrial DNA mutation at nucleotide position 15257, a primary mutation associated with Leber's hereditary optic neuropathy. DESIGN AND PATIENTS: Clinical and historical data were collected for 24 visually symptomatic patients from 20 independent pedigrees with the 15257 mutation. RESULTS: Fundoscopic examination in three patients who presented with acute, bilateral visual loss revealed retinal pigment epithelial changes in the maculae accompanied by normal-appearing optic discs. The conditions of two of these patients were initially diagnosed as Stargardt's disease, and subsequent molecular genetic analysis revealed the presence of the 15257 mutation. The third patient underwent molecular genetic analysis several months after presenting with a presumed maculopathy. Two of the patients also demonstrated evidence of a concurrent optic neuropathy. CONCLUSIONS: The association of macular changes with Leber's hereditary optic neuropathy-associated mitochondrial DNA mutation has not been previously reported. The mitochondrial DNA mutation at nucleotide position 15257 may cause a maculopathy as well as the typical optic neuropathy usually seen in Leber's hereditary optic neuropathy. A subset of patients whose conditions were diagnosed as Stargardt's disease may harbor a mitochondrial DNA mutation. These three cases illustrate the importance of molecular genetic testing in some atypical cases of optic neuropathies and maculopathies.

Leber's hereditary optic neuropathy masquerading as tobacco-alcohol amblyopia.

OBJECTIVE: To determine the frequency of known primary mitochondrial DNA (mtDNA) mutations for Leber's hereditary optic neuropathy (LHON) in patients previously diagnosed as having tobacco-alcohol amblyopia. DESIGN: A case series of 12 patients with tobacco-alcohol amblyopia. Follow-up ranged from 2 months to 15 years. SETTING: Tertiary care. PATIENTS: Twelve patients diagnosed as having tobacco-alcohol amblyopia, based on the classic clinical presentation, were tested for all the known primary mtDNA mutations associated with LHON. All patients had a history of heavy alcohol or tobacco use or both. Twelve other patients who fit inclusion criteria were unable to be contacted or refused to participate in the study. MAIN OUTCOME MEASURES: Presence of a known primary mutation for LHON at nucleotide positions 11778, 3460, 15257, or 14484 of mtDNA. RESULTS: Two (17%) of 12 patients previously diagnosed as having tobacco-alcohol amblyopia tested positive for known LHON genetic mutations, one for the 11778 mutation and one for the 3460 mutation. CONCLUSIONS: The diagnosis of LHON should be considered in all patients diagnosed as having tobacco-alcohol amblyopia, particularly those with visual acuities of 20/200 or less. The availability of molecular genetic testing for LHON now allows confirmation of the diagnosis of LHON in patients who otherwise may be misdiagnosed.

Heteroplasmy in Leber's hereditary optic neuropathy.

OBJECTIVES: To determine the incidence and clinical significance of peripheral blood heteroplasmy and the presence of normal and mutant mitochondrial DNA in Leber's hereditary optic neuropathy through evaluation of a large series of families with the 11778 mutation and to evaluate the pattern of transmission of heteroplasmy. DESIGN: We studied heteroplasmy in 75 visually symptomatic patients with the 11778 mutation and in 101 asymptomatic family members. We compared the incidence of heteroplasmy in these two groups, collected clinical information for each symptomatic patient, and calculated the incidence of heteroplasmy within each generation of the pedigrees. RESULTS: We detected heteroplasmy in 24 (14%) of the 176 persons tested. Kaplan-Meier life-table analysis suggests that heteroplasmic persons are more likely to remain asymptomatic than those who are homoplasmic mutant (males, P = .17; females, P = .14). However, heteroplasmic persons who become symptomatic do not seem to differ clinically from symptomatic patients who are homoplasmic mutant. Pedigree analysis reveals a strong tendency for progression from heteroplasmy toward homoplasmy in subsequent generations (P = .001). CONCLUSION: Heteroplasmy for the 11778 mutation seems to play a role in the clinical expression of Leber's hereditary optic neuropathy and tends to progress toward homoplasmy in successive generations.

Leber's hereditary optic neuropathy. Clinical manifestations of the 14484 mutation.

OBJECTIVE: To define the clinical features of Leber's hereditary optic neuropathy associated with the 14484 mitochondrial DNA mutation and to compare these features with those associated with three other pathogenetic mutations. DESIGN AND PATIENTS: Clinical and historical data were collected from 19 visually symptomatic patients from 17 independent pedigrees with the molecularly confirmed 14484 mutation. MAIN OUTCOME MEASURES: Demographic features, age of onset of visual loss, nadir of visual acuity, occurrence and timing of visual recovery, family history of visual loss, and associated medical and environmental conditions. RESULTS: Clinical characteristics associated with the 14484 mutation are similar overall to those of the three other primary mutations. One notable distinguishing feature is the higher incidence of visual recovery among patients with the 14484 mutation. Thirty-seven percent of our patients experienced visual recovery compared with 5% with the 11778 mutation (P < .001), 22% with the 3460 mutation, and 29% with the 15257 mutation. The average age of onset of visual symptoms for the patients with the 14484 mutation who had visual recovery was younger than for those without recovery (19.6 vs 30.6 years). Thirteen of the 19 patients had a history of metabolic disturbance, trauma, or substance abuse. CONCLUSIONS: Leber's hereditary optic neuropathy associated with the 14484 mitochondrial DNA mutation may have a better prognosis for visual recovery. The phenotypic expression of the 14484 mutation may be influenced by concurrent medical and environmental factors. Molecular genetic testing in suspected Leber's hereditary optic neuropathy is useful to confirm the diagnosis and to assess visual prognosis.

Tonic pupil and orbital glial-neural hamartoma in infancy.

PURPOSE/METHODS: Tonic pupils in early childhood are rare. We studied an otherwise healthy 31/2-month-old girl who had a right pupil that was poorly reactive to light, without other signs of oculomotor nerve palsy. RESULTS/CONCLUSIONS: Constriction of the right pupil after instillation of 0.125% pilocarpine eyedrops confirmed denervation hypersensitivity, consistent with a tonic pupil. There was no strabismus or proptosis. A magnetic resonance imaging scan demonstrated a right orbital mass, interposed between the lateral and inferior recti muscles. Biopsy was consistent with a benign, glial-neural hamartoma. Thus, in this young patient, a tonic pupil was associated with a benign orbital mass.

Crush injuries to the head in children.

Although the majority of head injuries in children and adults involve dynamic loading conditions, some patients suffer static loading. Static loading occurs when forces are applied slowly to the head, and it produces a much different pattern of injuries. Crush injuries are usually described in the context of industrial accidents, but in our experience, these injuries are not rare in children. We report a series of seven crush injuries in young children admitted during a period of 29 months and describe our experience in the evaluation and treatment of this complex entity. Patient ages ranged from 15 months to 6 years. In four cases, the child's head was run over by a motor vehicle backing up in a driveway or parking lot. In the three other patients, the static loading occurred when the child climbed or pulled on a heavy object, which then fell over with the child and landed on the child's head. One child with cervicomedullary disruption died shortly after his arrival at the hospital. The others showed varying degrees of soft tissue injury to the face and scalp, with Glasgow Coma Scale scores ranging from 7 to 15. Computed tomograms and magnetic resonance images showed multiple and often extensive comminuted calvarial fractures, as well as subarachnoid and parenchymal hemorrhages. All patients had basilar cranial fractures. There was one cervical spine injury but no major vascular injuries. One child had pituitary transection, four had cranial nerve palsies, and another developed a delayed cerebrospinal fluid rhinorrhea 18 months after injury. All children made good cognitive recoveries, with some having relatively mild fixed focal deficits.(ABSTRACT TRUNCATED AT 250 WORDS)

Oil-drop cataracts.

The oil-drop cataract is a common yet often overlooked cause of progressive vision loss. Although the nuclear change can be subtle on slitlamp biomicroscopic examination, retinoscopy reveals the classic oil droplet silhouetted against the red reflex. We present seven patients with oil-drop cataracts referred for neuro-ophthalmologic evaluation because of unexplained vision loss. All had been evaluated by multiple physicians and had had extensive diagnostic testing. The patients were between 36 and 69 years old with visual acuities from 20/20 to 20/400. The neuro-ophthalmologic evaluation in all patients was normal except for lenticular nuclear changes, best appreciated with retinoscopy.

Oral mucous membrane grafts for corneal protection to permit prosthetic shell wear.

Conjunctival flaps are commonly used to cover the cornea in patients who otherwise can not tolerate a scleral shell. An alternative method of protecting the cornea, oral mucous membrane grafting, is described herein. Ten patients had oral mucous membrane grafting to the cornea. Patients ranged from 5 months to 47 years of age. Diagnoses included partial cryptophthalmia, microphthalmia, congenital orbital fibrosis syndrome, juvenile active ossifying fibroma, and trauma. All patients had poor visual function in the affected eye. Patients were either intolerant of scleral shell wear or had other contraindications to the use of a shell over an unprotected cornea. Following mucous membrane grafting (follow-up, 1-3 years), all patients were successfully fitted with prostheses and obtained good cosmetic results.

The natural history of Leber's congenital amaurosis. Age-related findings in 35 patients.

The authors studied 35 patients with Leber's congenital amaurosis and assessed visual acuity, fundus appearance, and systemic findings. The patients were arbitrarily divided into five age groups. Visual acuities were comparable at all ages. Of 22 patients seen for follow-up examinations (mean length of follow-up, 5 years), vision worsened slightly in only 4 patients (3 with macular coloboma-like lesions and 1 with keratoconus). Fifty percent of retinal examinations in patients younger than 1 year of age were normal. With increasing age, retinal pigmentary changes became evident. All but four patients seen on more than one occasion developed progressive retinal/retinal pigment epithelium changes. Cataracts (5 patients) and keratoconus (3 patients) were present only in older patients (9 to 33 years of age). In Leber's congenital amaurosis, which probably comprises a number of genetically heterogenous conditions, visual acuity remains stable despite progressive retinal pigmentary changes. The subgroup of patients with macular colobomas, however, may develop progressive decrease in vision. Cataracts and keratoconus are additional factors contributing to visual impairment in older patients.

Congenital and acquired anophthalmia.

Anophthalmia is an absence of ocular tissue in the orbit. Important aspects in the diagnosis, evaluation, and treatment of both congenital and acquired anophthalmic patients are reviewed. Congenital and acquired anophthalmia differ in etiology, but many concepts of management can apply to either category. Specific steps in the evaluation and treatment including the proper timing for medical and surgical intervention will be discussed. The major goals for the ophthalmologist are to optimize motility and symmetry of the eyelids and orbit and coordinate efforts with other medical specialties.

Unilateral dermis-fat graft implantation in the pediatric orbit.

The purpose of this study was to evaluate the role of the dermis-fat graft (DFG) as an orbital implant in the pediatric age group. A retrospective study was made of a series of 16 patients who had undergone unilateral orbital implantation of a DFG. The ages of the patients at the time of surgery ranged from 2 months to 17 years, with followup ranging from 2 to 15 years. Growth of the graft was clinically apparent in the younger children. Increasing proptosis required surgical debulking of the graft in six of eight children who were 4 years old or younger at the time of DFG implantation. None of the eight children who were 9 years or older at the time of DFG implantation required surgical debulking. Indeed, five of the older patients demonstrated some degree of graft atrophy. Dermis-fat grafts placed in the orbits of young children appear to grow after implantation. This growth of the implant may help stimulate orbital growth, potentially leading to more symmetry between the involved and uninvolved sides.

Prominent proptosis in childhood thyroid eye disease.

BACKGROUND: Orbital signs and symptoms occur in approximately one half of children with Graves disease, but the symptoms are usually minor and limited to the eyelids. Prominent proptosis is uncommon in children with this disorder. METHODS: Review of eight children with prominent proptosis associated with thyroid eye disease. Four patients were treated at the Children's Hospital of Philadelphia, the other four at the Columbia Presbyterian Medical Center. RESULTS: At initial presentation, children ranged in age from 3 to 16 years. There were five girls and three boys. Seven of eight children had hyperthyroidism at ophthalmic presentation. Four patients had restrictive myopathy, and all of the seven patients who underwent neuroimaging had extraocular muscle enlargement. Five patients were treated with lubrication. Two underwent orbital fat decompression. One patient had thyroid eye disease and myasthenia gravis. CONCLUSIONS: Proptosis in childhood thyroid eye disease usually is associated with a hyperthyroid state. The proptosis may be dramatic, but corneal exposure and restrictive myopathy are seen in only some of the patients. Neuroimaging shows enlarged extraocular muscles. Most children with this complication can be treated conservatively with topical lubrication, but orbital fat decompression may be considered in patients with more advanced conditions.