Ophthalmic Abnormalities Research Articles

Ocular manifestations of HIV infection.

Ophthalmic abnormalities are common in HIV-infected patients. Serious ophthalmic diseases often result from opportunistic infections and can cause blindness in the absence of prompt diagnosis and therapy. We review recent advances in the diagnosis and management of HIV-associated ocular disease, including cytomegalovirus retinitis, the leading cause of vision loss in HIV-infected patients. The widespread use of highly active antiretroviral therapy (HAART) over the past 3 years has reduced the morbidity and mortality associated with HIV infection. HAART has dramatically altered the incidence and natural history of many opportunistic infections, and we discuss the impact of HAART on ophthalmic disease.

Ophthalmic abnormalities in patients with cutaneous T-cell lymphoma

ObjectiveTo determine the frequency of ophthalmic abnormalities in patients with cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome) and T-cell lymphoma involving the skin and to describe the clinical course of the disease with selected examples. DesignRetrospective, clinic-based, cross-sectional study. ParticipantsA computerized diagnostic retrieval system was used to identify all patients with T-cell lymphoma involving the skin who were examined at the Mayo Clinic (Rochester, Minnesota) between January 1, 1976 and December 31, 1990. The medical records of affected patients were reviewed. Main outcome measuresIdentification of ophthalmic abnormalities. ResultsDuring the 15-year interval from 1976 through 1990, cutaneous T-cell lymphoma was diagnosed in 2155 patients. Of these, 42 (1.95%; 26 male and 16 female) had at least one ophthalmic abnormality attributable to the disease. The diagnoses in these 42 patients were mycosis fungoides in 19, clinical variants of T-cell lymphoma of the skin (most commonly peripheral T-cell lymphoma) in 11, and Sézary syndrome in 12. Cicatricial eyelid ectropion was the most common finding, affecting 17 (40.4%) of the 42 patients. Thirty-seven patients had findings that, although probably not a direct consequence of cutaneous T-cell lymphoma, have been cataloged in previous studies. ConclusionAlthough ophthalmic abnormalities in patients with cutaneous T-cell lymphoma are relatively uncommon, the manifestations of the disease are diverse and frequently difficult to treat.

Loss-of-function mutations in the LIM-homeodomain gene, LMX1B, in nail-patella syndrome.

Nail-patella syndrome (NPS) is an inherited developmental disorder most commonly involving maldevelopment of the fingernails, kneecaps and elbow joints. NPS exhibits wide variation in phenotypic expression within and among families with respect to these features. Other skeletal abnormalities such as hip dislocation and club foot have also been reported in some individuals with NPS. There is an association between NPS and renal disease, and between NPS and open-angle glaucoma (OAG), but it is not known whether mutations in a single gene cause the observed skeletal, renal and ophthalmic abnormalities. Recently, LMX1B , a transcription factor of the LIM-homeodomain type with homologs that are important for limb development in vertebrates, was mapped to the same general location as NPS at 9q34. We sequenced a large segment of LMX1B from the genomic DNA of probands from four families with NPS and OAG, and identified four mutations: two stop codons, a deletion causing a frameshift and a missense mutation in a functionally important residue. The presence of these putative loss-of-function mutations in the DNA of individuals with NPS indicates that haploinsufficiency of LMX1B underlies this disorder. These findings help to explain the high degree of variability in the NPS phenotype, and suggest that the skeletal defects in NPS are a result of the diminished dorsoventral patterning activity of LMX1B protein during limb development. The results further suggest that the NPS and OAG phenotypes in the families studied result from mutations in a single gene, LMX1B.

Ophthalmic abnormalities in homocystinuria: the value of screening.

Homocystinuria, a genetic metabolic abnormality, eventually causes a variety of ocular and other pathologies if not treated. To evaluate the results of screening newborns for homocystinuria, we compared ophthalmic outcomes for two groups of homocystinuria patients who had been diagnosed either at birth or later than 6 weeks. Nineteen patients had been screened and diagnosed shortly after birth, with treatment instigated before 6 weeks of age (mean follow-up and age 10.8 years; median 11 years). Eight of 17 were myopic; 13 of 15 had good vision in both eyes; one had lens subluxation. The second group of 17 patients were diagnosed later than 6 weeks, often (12 patients) because of ocular problems (mean follow-up 8.3 years; mean age 19.4 years; median age 16 years). Visual function varied from 6/6 (4 patients) to less than 6/36 (4 patients); 3 eyes had no perception of light. Thirteen patients had lens subluxation or dislocation. Early diagnosis and treatment of homocystinuria is advantageous.

Ophthalmologic findings in long-chain 3-hydroxyacyl-Coa dehydrogenase deficiency caused by the G1528C mutation: A new type of hereditary metabolic chorioretinopathy

Objective The purpose of the study was to determine the nature and course of ophthalmic abnormalities in long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, a recently discovered disorder of mitochondrial fatty acid β-oxidation. Study design The study design was a cohort (case series). Participants A retrospective review of the records of 15 children who had died during their first 2 years was performed. Also performed were a longitudinal reanalysis and cross-sectional clinical examination of four long-term survivors aged 5 to 31 years. Main outcome measures Visual acuity, refraction, visual fields, ophthalmoscopy, fluorescein angiography, biometry, corneal topography, electroretinography (ERG), visual-evoked potentials (VEPs), color vision, and dark adaptation were measured. Results In seven children, ophthalmoscopic findings were within normal limits at 3 days to 13 months of age (median, 4.8 months). In 11 children, a granular retinal pigment epithelium (RPE), with or without pigment clumping in the macula, was seen at 4 months to 5 years of age (median, 9 months). Two long-term survivors, 16 and 31 years of age, eventually had circumscribed atrophy of the choroid, RPE, and retina, which coincided with a posterior staphyloma type 1. They had progressive axial myopia starting at 6 and 12 years of age and later paracentral scotomas leading to poor central vision. They suffered from early difficulty with mesopic vision, glare, and a severe generalized color vision deficiency that started as a tritanomaly. A third survivor was mildly myopic at 5 years of age. All four surviving patients had visually insignificant, flake-like supranuclear opacities in the lens. The ERG initially was normal but deteriorated during the first decade and later was unrecordable. The VEP responses remained fairly normal. Initially, angiography showed no blockade of the choroidal fluorescence because of the thin RPE. Filling of choroidal vessels was delayed, and the choriocapillaris and, later, larger choroidal vessels in the posterior pole became nonperfused. Conclusions In LCHAD deficiency, the fundus is normal at birth (stage 1). Soon, however, pigment dispersion occurs in the RPE (stage 2), followed by circumscribed chorioretinal atrophy, occlusion of choroidal vessels, and deterioration of central vision, often with relative sparing of the peripheral fundus (stage 3). Finally, posterior staphylomas and central scotomas may develop (stage 4). Developmental cataract, progressive myopia, and deterioration of visual fields and color vision are new findings in LCHAD deficiency. The chorioretinopathy and abnormal ERG precede the development of myopia and posterior staphyloma, which, in turn, coincide with the loss of macular vision. The authors postulate that the RPE or choriocapillaris is primarily affected. Awareness of the characteristic ocular features is important because of an opportunity for dietary treatment, genetic counseling, and prenatal diagnosis.

Autonomic neurotoxicity of jellyfish and marine animal venoms.

Venoms and poisons of jellyfish and other marine animals can induce damage to the human nervous and circulatory systems. Clues to the pathogenesis and clinical manifestations of these lesions can be obtained from data of human envenomations and animal experimentation. Because many investigators are unaware that marine animal venoms have autonomic actions, this paper aims to elucidate the broad antagonistic or toxic effects these compounds have on the autonomic nervous system. Marine venoms can affect ion transport of particularly sodium and calcium, induce channels or pores in neural and muscular cellular membranes, alter intracellular membranes of organelles and release mediators of inflammation. The box jellyfish, particularly Chironex fleckeri, in the Indo-Pacific region, is the world's most venomous marine animal and is responsible for autonomic disorders in patients. The symptoms induced by these venoms are vasospasm, cardiac irregularities, peripheral neuropathy, aphonia, ophthalmic abnormalities and parasympathetic dysautonomia. Cases of Irukandji syndrome, caused by the jellyfish Carukia barnesi, have symptoms that mimic excessive catecholamine release. Coelenterate venoms can also target the myocardium, Purkinje fiber, A-V node or aortic ring. Actions on nerves, as well as skeletal, smooth or cardiac muscle occur. Recent studies indicate that the hepatic P-450 enzyme family may be injured by these compounds. The multiplicity of these venom activities means that a thorough understanding of the sting pathogenesis will be essential in devising effective therapies.

Ophthalmologic Changes in Patients with Cerebral Palsy

Introduction and Objective:Ophthalmic changes in cerebral palsy (CP) are a frequent cause of visual deficits. The object of this study was to determine the frequency, type and characteristics of ophthalmic abnormalities in patients with cerebral palsy and to correlate these findings with the type and severity of the cerebral palsy present.Subjects and Methods:A prospective, cross sectional and observational study of 110 patients with a confirmed diagnosis of CP was designed. Patients were given a complete ophthalmologic examination including a cycloplegic refraction and a dilate fundus examination.Results:The most frequent ocular problems were: refractive problems in 109 (99%), ocular motility disturbances in 73 (66.3%), optic atrophy in eleven (14.2%) and anterior segment disturbances in six (7.7%). Correlation between the severity and type of CP showed that optic atrophy is more frequent in patients with spastic quadriparesis. We did not find any other correlations with the other ophthalmic abnormalities.Conclusion:Refractive errors, alterations in ocular motility and optic atrophy are characteristic ophthalmologic findings in patients with CP.

Ophthalmic Eponyms From the Mayo Clinic

Ophthalmic Eponyms From the Mayo Clinic

Multisystem Abnormalities in a Patient with Papillon-Lefevre Syndrome

Multisystem Abnormalities in a Patient with Papillon-Lefevre Syndrome

OPHTHALMIC DISORDERS IN CHILDREN WITH DOWN SYNDROME

The goal of this study was to determine the frequency of ophthalmic disorders in a group of young children with Down syndrome who were unselected for ophthalmic abnormalities, and to determine whether examination by a pediatric ophthalmologist should become standard practice. Of 77 children referred to a Down syndrome clinic at a teaching hospital and evaluated by a pediatric ophthalmologist, 61 per cent had ophthalmic disorders needing treatment and monitoring. Furthermore, the percentage of children with ophthalmic disorders increased with age, from 38 per cent in the two- to 12-month-old group to 80 per cent in the five- to 12-year-old group. The authors conclude that children with Down syndrome should be evaluated by a pediatric ophthalmologist in the first six months of life and annually thereafter.

Single missense mutation in the tyrosine kinase catalytic domain of the RET protooncogene is associated with multiple endocrine neoplasia type 2B.

Multiple endocrine neoplasia type 2B (MEN 2B) is a human cancer syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytomas, mucosal neuromas, ganglioneuromas of the intestinal tract, and skeletal and ophthalmic abnormalities. It appears both as an inherited disorder and as de novo disease. Sequence analysis of germ-line DNA from MEN 2B patients revealed the existence of the same point mutation in the RET protooncogene in 34 unrelated individuals. This sequence difference was not observed in 93 unaffected individuals, including the normal parents of 14 de novo MEN 2B patients. The mutation (ATG-->ACG) results in the replacement of methionine with threonine within the catalytic core region of the tyrosine kinase domain. We propose that this amino acid replacement effects substrate interactions and results in dominant oncogenic activity by the RET protein. Missense mutations in the extracellular ligand-binding domain of the RET protooncogene previously have been associated with two other disorders [MEN 2A and familial MTC (FMTC)] in which MTC is observed. MEN 2B represents the third form of heritable MTC known to be an allele of RET. Alterations in two different functional domains of the putative receptor protein tyrosine kinase are implicated in development of MTC.

Developmental changes in the optic nerve related to ethanol consumption in pregnant rats: Analysis of the ethanol‐exposed optic nerve

Visual impairment is one of the most common ophthalmic abnormalities in fetal alcohol syndrome. Pathologic changes in optic nerve development related to alcohol consumption could be involved in this dysfunction. In order to assess the consequences of pre- and postnatal exposure to alcohol on the developing optic nerve, we administered an ethanol-containing liquid diet (5% w/v) before and during gestation and throughout lactation to rats and their offspring. A group of control animals were kept on a pair-fed isocaloric diet. The optic nerves were obtained at key stages from fetuses (21 days of gestation) and pups (4, 7, 14, 21 and 28 postnatal days). Samples of the optic nerve cross-section, behind the eyeball, were processed for analysis of gliogenesis, myelinogenesis, axonal growth, and remodelling events, using light and electron microscopy. Qualitative, morphometric, and immunocytochemical analyses, alternatively using anti-GFAP and anti-MBP antibodies, were carried out. Optic nerve cross-sections from prenatal and postnatal alcohol-exposed rats showed a decrease in size. Ultrastructural alterations and retarded development in macroglial cells, optic axons, and myelin sheath were also observed. The most prominent abnormalities were: damage of cytoplasmic organelles and disorganization of cytoskeleton in astrocytes; a decrease in free ribosome density and nuclear membrane inclusions in oligodendrocytes; and fragmentation of lamellae, aberrant myelin sheaths and intralamellar inclusions in myelin. These findings suggest that alcohol abuse during pregnancy is teratogenic to the optic nerve and closely related to the altered visual function.

Complications of the naevoid basal cell carcinoma syndrome: results of a population based study.

There are many potential complications which have been reported in association with the naevoid basal cell carcinoma syndrome. We have been able to show the relative frequencies of these problems in a population based study of 84 cases in the north west of England. The major complications of basal cell carcinomas and jaw cysts occur in over 90% of patients by 40 years of age, but may both occur before 10 years of age. Less well described complications are ovarian calcification or fibroma (24%), medulloblastoma (5%), cardiac fibroma (3%), cleft palate (5%), and ophthalmic abnormalities such as squint or cataract (26%). This study more clearly defines the possible complications of the syndrome and gives clearer guidelines for counselling and screening affected and at risk persons.

Photorefraction Screening in Premature Infants

Photorefraction is a screening technique capable of detecting potentially amblyogenic ophthalmic abnormalities. This screening technique was included as part of a longitudinal outpatient follow-up program of premature infants. The purpose of this investigation is to test the applicability of this screening method in a population of infants at risk for visual compromise. One-hundred eighty-two premature infants older than 3 months chronologic age were screened using a commercially available, off-axis photorefraction device. Ophthalmic examinations were performed concomitant with each photorefraction. In most cases, photorefractions were performed before and after administration of cycloplegic medications. All photorefractions were analyzed by an observer masked to the results of the ophthalmic examination. For the 182 patients, the mean birth weight and mean gestational age were 1034.5 g and 28.2 weeks, respectively. The prevalence of ophthalmic abnormalities in the study population was 18%. Sensitivity and specificity rates for the overall screening were 77% and 90%, respectively. Photorefractions were analyzable in 77% of patients studied, with the remaining 23% of our study population unsuccessfully screened. Very young infants (younger than 3 months corrected age) were particularly difficult to photograph, as evidenced by the preponderance of these patients (85%) in the nonanalyzable group. The readability of photorefractions in black infants was improved when cycloplegia was used for the photorefraction. Photorefraction screening was an acceptable method of screening for ophthalmic abnormalities in a group of premature infants. Future studies of photorefraction screening techniques in premature infants will need to improve the success rate in young infants, perhaps by improving the fixation device.

Ophthalmic assessment of physically disabled children attending a rehabilitation centre

A retrospective analysis was conducted of 397 children, ranging in age from 2 to 19 years, attending the Regency Park Centre for Young Disabled in Adelaide. The disorders represented included cerebral palsy, head injury, spina bifida, severe speech and/or language disorders, muscular dystrophy and a number of less common conditions. The incidence of significant ophthalmic abnormalities in this population was 51%, with the highest incidence being 69 and 62% among children with head injury and cerebral palsy, respectively. Children with severe speech and language disorders had an incidence of 24%. Overall, routine examinations revealed previously unsuspected significant eye abnormalities in 31% of the children. A complete ophthalmic examination should be part of the evaluation of all physically disabled children to ensure early identification and treatment of abnormalities, and to optimize rehabilitation.

Ocular manifestations of Noonan syndrome.

Noonan syndrome is a genetic condition inherited in an autosomally dominant manner, characterised by congenital heart disease, short stature, abnormal facies and the somatic features of Turner's syndrome, but a normal Karyotype. The ophthalmological and orthoptic findings on 58 patients with Noonan syndrome are reported. External features were hypertelorism (74%), downward sloping palpebral apertures (38%), epicanthic folds (39%) and ptosis (48%). The orthoptic examination revealed strabismus in 48%, refractive errors in 61%, amblyopia in 33%, and nystagmus in 9% of cases. Sixty-three per cent of cases had anterior segment changes consisting of: Prominent corneal nerves (46%), anterior stromal dystrophy (4%), cataracts (8%) and panuveitis (2%). Fundal changes occurred in 20% of the study group, including optic nerve head drusen, optic disc hypoplasia, colobomas and myelinated nerves. Forty-seven per cent required non surgical treatment and a further 16% had undergone surgery for strabismus or ptosis. Only three patients had no visual defects. With such a high incidence of ophthalmic abnormalities it is clearly important that children with Noonan syndrome are screened by an ophthalmologist at an early age.

Spontaneous Ophthalmic Lesions in Young Sprague-Dawley Rats.

Eight hundred eight Sprague-Dawley rats were examined for ophthalmic abnormalities during a pretest period in various preclinical safety assessment studies. Persistent pupillary membrane, corneal crystal, healed minor trauma, synechia, coloboma of the iris, lens luxation, cataract, persistent hyperplastic primary vitreous, vitreous hemorrhage, coloboma of the optic disc or choroid, remnant of hyaloid arterial system, retinal hemorrhage, retinal detachment, retinal folding and choroidal defect were observed. The incidences of corneal crystal, synechia, and nuclear cataract in this survey were higher than those reported previously. On the other hand, retinal folding in this survey was less common than that reported previously. These results suggest that background data of eye problems in albino rats should be accumulated in each own laboratory colony. In addition, since spontaneous eye problems are common in young albino rats, elimination of rats with ophthalmic abnormalities from study groups by an ophthalmic examination during a pretest period would facilitate to evaluate toxicity potential of test compounds in safety assessment studies.

Hyperopia in Complicated Leber's Congenital Amaurosis

We studied the refractive status of 13 children with Leber's congenital amaurosis. Seven had the disease complicated by neurological or other systemic abnormalities, while the other 6 patients had only ophthalmic abnormalities. All 13 patients were hyperopic. The magnitude of hyperopia did not differ significantly between the complicated and uncomplicated groups. Therefore, one cannot, as previously suggested, use the presence of high hyperopia to differentiate an uncomplicated form of Leber's congenital amaurosis from one complicated by neurologic or other systemic abnormalities. The concurrence of hyperopia with Leber's congenital amaurosis should not steer the physician away from careful neurologic systemic or biochemical evaluation of the child.

Ocular and Systemic Findings in the Aarskog (Facial-digital-genital) Syndrome

The Aarskog (facial-digital-genital) syndrome is an X-linked disorder in which short stature is accompanied by hypertelorism, digital anomalies, and shawl scrotum. Except for hypertelorism and blepharoptosis, ophthalmic abnormalities have been rarely noted in this condition. We examined four patients who had Aarskog syndrome and unilaterally or bilaterally decreased vision on initial examination. Three family members had V-pattern esotropia, latent nystagmus, inferior oblique overaction, and amblyopia. A fourth patient had bilateral blepharoptosis and severe astigmatism. Other ocular features included hyperopia, anisometropia, deficient ocular elevation, blue sclerae, and posterior embryotoxon. These findings underscore the need for ophthalmic examination in asymptomatic patients with Aarskog syndrome to rule out treatable causes of visual loss.

The Ophthalmic Manifestations and Treatment of the Amniotic Band Syndrome

The amniotic band syndrome is an unusual cause of craniofacial deformities. The syndrome, which is initiated by rupture of the amnion, results in an unpredictable combination of compression deformities of the fetus, construction or amputation defects of the extremities, and craniofacial clefting deformities. The type and extent of ophthalmic abnormalities are dependent on the band location and timing. They include a combination of bony orbital clefts or hypertelorism; lid anomalies such as colobomas, ptosis, and ectropion; lacrimal outflow obstruction; and globe involvement. We review the clinical course of 14 patients diagnosed with, or suspected as having, this syndrome and describe the methods of treatment. In most instances, multiple surgical procedures were required to restore function. Satisfactory cosmesis proved more difficult to obtain.