Apolipoprotein A-I and B distribution in the human cornea.

PURPOSE: To determine the presence and localization of apolipoprotein A-I, a marker for high density lipoprotein, and apolipoprotein B, a marker for low density lipoprotein, in human cornea; to examine the relationship of these lipoprotein markers with areas of lipid accumulation in the cornea. METHODS: A-I and B apolipoproteins were localized in frozen sections of human corneas with specific monoclonal antibodies using avidin-biotin immunoperoxidase labelling. Corneal lipid was colocalized with apolipoproteins by oil red 0 staining of immunostained sections. RESULTS: Staining data showed that apolipoprotein B and lipid accumulated in the extracellular spaces of peripheral corneal stroma. However, their distributions were not coincident. The posterior region of peripheral corneal stroma (including Descemet's membrane) often contained lipid without immunodetectable apolipoprotein B. Unexpectedly, apolipoprotein A-I was associated with many keratocytes throughout the cornea in addition to an extracellular distribution heaviest in peripheral cornea. CONCLUSIONS: Lipid deposits lacking apolipoprotein B in peripheral cornea suggest that if accumulated corneal arcus lipid is derived from extracellular deposition of plasma low density lipoprotein, the low density lipoprotein is altered such that it looses its immunoreactive apolipoprotein B. The unexpected association of apolipoprotein A-I with keratocytes suggests that these cells are either taking up or synthesizing a protein sharing an immunoreactive epitope with apolipoprotein A-I.

Anterior corneal dystrophy with dyscollagenosis (Reis-Bücklers type?).

Anterior corneal dystrophies involving Bowman's membrane and anterior stroma include several subtypes of uncertain etiology: the Reis-Bückler, Thiel-Behnke, Grayson-Wilbrandt, and "honeycomb" dystrophies. The clinical and pathologic features of these dystrophies overlap to such a degree that they may represent variations of the same entity. Typically, they all present symptoms beginning in childhood, have a dominant pattern of heredity, and manifest painful, recurrent corneal erosions. Some cases have also been interpreted as representing macular and granular dystrophy. In the present report, we describe a pedigree of affected patients whose corneal dystrophy shared many of the clinical and pathologic features of the Reis-Bücklers and allied subtypes but which differ from all in causing visual symptoms late in life and with minimal signs of recurrent erosion. Histopathology revealed a thickening of the anterior stroma by the addition of a partially disorganized and degenerating tissue in which collagen Type III (fetal or repair collagen) is intermixed with the normal (mature) Type I collagen in the entire stroma. This is accompanied by irregular swelling of the basal epithelial cells and hyperplasia of the basement membrane (collagen Type IV, laminin and fibronectin), suggesting an aberrant influence of the epithelium on collagen synthesis.

Corneal opacity in LCAT disease.

Deficiency of lecithin:cholesterol acyltransferase, LCAT disease, is one of the dyslipoproteinemias with characteristic lipid deposits in the cornea. The present report documents the clinicopathologic abnormalities of one case in which a full-thickness corneal specimen was obtained at the time of corneal transplantation. The characteristic clinical abnormality was a progressive corneal opacification with a peripheral arcus that extended into the sclera. The pathologic abnormality consisted of vacuoles prevalent in the anterior corneal stroma by light microscopy and containing extracellular, membranous deposits by electron microscopy. These observations confirm and supplement the previous six pathologic reports of corneal changes in LCAT disease and demonstrate, for the first time, histopathologic evidence of unesterified cholesterol in the corneal stroma of LCAT disease.

Apparent unilateral visual neglect in MPTP-hemiparkinsonian monkeys is due to delayed initiation of motion.

Monkeys made hemiparkinsonian by infusion of a solution of MPTP into one carotid artery appeared to ignore food presented from the contralateral side. Initial observations suggested neglect of visual stimuli presented as fruit treats by automated delivery system in the half-field contralateral to MPTP treatment. Further studies in which fruit treats were left in the 'neglected' visual field indicated that this apparent neglect, unlike neglect attending cortical lesions, was rather a marked delay in initiating movements (unilateral hypokinesia). These observations may explain apparent subcortical neglect and are consistent with the known role of nigrostriatal dopaminergic neurones in movement regulation. This is a useful animal model in which difficulties in initiation of movement (hypokinesia). a cardinal symptom of Parkinson's disease, can be studied separately from other deficits in motor performance.

[Paraneoplastic retinopathy simulating cone dystrophy with achromatopsia]. / Paraneoplastiche Retinopathie unter dem klinischen Bild einer Zapfendystrophie mit Achromatopsie.

A 72-year-old woman developed recurrent blindness on exposure to bright light (sunlight). Examination revealed total achromatopsia; bilateral central scotomas, predominant suppression of the cone response by electroretinography, and narrowing of the retinal arteries on ophthalmoscopy. The general examination revealed a pelvic tumor that later proved to be a pleomorphic carcinoma of presumed uterine origin. The patient died of metastatic disease 9 months after the ocular symptoms developed. Histopathologic examination of the eyes revealed loss of the photoreceptors, most extensive in the macular regions, and selective loss of the cones from the rest of the retinas. No ocular metastases of inflammation were found. The changes described are interpreted as paraneoplastic retinopathy of autoimmune origin.

Clinical spectrum of Niemann-Pick disease type C.

Analysis of the neurologic symptomatology in 22 patients with Niemann-Pick disease type C revealed 3 phenotypes: (1) an early-onset, rapidly progressive form associated with severe hepatic dysfunction and psychomotor delay during infancy and later with supranuclear vertical gaze paresis, ataxia, marked spasticity, and dementia; (2) a delayed-onset, slowly progressive form heralded by the appearance, usually in early childhood, of mild intellectual impairment, supranuclear vertical gaze paresis, and ataxia, and later associated with dementia and, variably, seizures and extrapyramidal deficits; (3) a late-onset slowly progressive form distinguished from the 2nd pattern by later age of onset (adolescence or adulthood) and a much slower rate of progression. The existence of the 1st and 2nd phenotypes within the same sibship suggests that they are variant expressions of the same clinicopathologic disorder. Niemann-Pick disease type C should be considered not only in infants and children who present with organomegaly and a progressive neurodegenerative course, but also in adolescents and adults who have insidiously progressive neurologic dysfunction and only slight organomegaly. Associated with the disease is a marked deficiency in the ability of cultured fibroblasts to esterify exogenously supplied cholesterol. Assay of this deficiency is particularly useful for confirming the diagnosis in patients with atypical presentation.

Late corneal opacities in the syndrome of interstitial keratitis and vestibulo-auditory symptoms.

Progressive clouding of the cornea may be a delayed complication of the interstitial keratitis-vestibuloauditory syndrome. Two illustrative cases are presented. The first case illustrates progressive opacification about aberrant vessels in the deep stroma presenting a characteristic dendritiform pattern. The second case shows that the opacification is due, in this case at least, to formation of connective tissue with inclusion of lipid crystals and fat along with the blood vessels. Descemet's membrane is also thickened several fold.

Asymmetry in congenital ocular motor apraxia.

A 10-month-old girl presented with apparently unilateral ocular motor apraxia (OMA). Electro-oculography confirmed an inability to generate a saccade for fixation or in response to an optokinetic or vestibular evoked stimulus to the right. Fixation and optokinetic saccades and vestibular evoked nystagmus were present to the left. Magnetic resonance imaging revealed a small cerebellar vermis but no localizing unilateral abnormality or tumour. Subsequent review of video recordings of 16 children with congenital OMA revealed that 5 demonstrated asymmetry in the generation of fixation saccades. Two of the five also demonstrated asymmetry of vestibular evoked nystagmus, and an additional child had optokinetic asymmetry.

Lest we forget: notes on reading Verhoeff's early correspondence.

Dr. Verhoeff's life and work are reexamined by the author in the light of his early correspondence. The letters remind us of the significant contributions of Dr. Verhoeff to ophthalmic pathology in America. His personal qualities, such as candor, ingenuity and intellectual honesty are recalled by his successor in the Howe Laboratory.

Prevention of ocular toxicity of carmustine (BCNU) with supraophthalmic intracarotid infusion.

Intracarotid administration of carmustine (BCNU) is an increasingly accepted therapeutic modality for primary brain tumors. Its beneficial effect on prolonging survival, however, is countered by its frequent delayed complication of retinal toxicity and severe visual loss, which reportedly occurs in approximately 70% of the patients. Since this complication probably results from increased flow of the drug into the ophthalmic artery, the authors have attempted to infuse BCNU via a small intracarotid catheter advanced beyond the origin of the ophthalmic artery. In a series of nine patients (average follow-ups, 10.7 months), the authors were successful in treating six patients with exclusively supraophthalmic infusions. None of these patients developed any ocular toxicity. From the remaining three patients, two patients received one infraophthalmic infusion with no retinal toxicity. The third patient, however, who received three infraophthalmic infusions, developed ipsilateral retinopathy. These results suggest that retinopathic complications of intracarotid BCNU can be avoided if the infusion catheter is advanced beyond the origin of the ophthalmic artery.

Near-evoked nystagmus in spasmus nutans.

Near-evoked nystagmus was evident in two children with spasmus nutans by clinical observation and electro-oculographic recording. In one child the nystagmus appeared to be evoked by fusional convergence and in the other by convergence-accommodation. These cases represent an atypical form of spasmus nutans in which the nystagmus is modulated by centers controlling visuomotor changes with near viewing.

Accessory cells in vessels of the paranatal human retina.

Retinas of the paranatal period contain two types of cell clusters that are generally believed to play a role in the developing vasculature. The more posterior cluster consists of angioblastic cells, which undergo lumenization to form the definitive vessels. Anterior to this cluster and separated from it by a distinct boundary are clusters of spindle cells extending a variable distance toward the periphery. These clusters of spindle cells maintain a fixed position relative to the angioblastic masses, without any admixture of the two. The precise function of the spindle cells in the vascularizing process has been a subject of controversy. We found evidence to identify them as glia and to suggest that their role is to provide an energy source for the developing retina as the hyaloid vessels recede and until the retinal vessels take over this function. It further appears that congenital failure of the vessels to develop may result in a persistence of these spindle cells, in the form of hyperplastic glia in the inner layers of the retina. Our study included normal eyes from full-term and premature infants and eyes from patients with retinopathy of prematurity (oxygen-related retinopathy), anencephaly, and other congenital anomalies.

Ex Errato Lux. Concept and development of the Verhoeff Society.

With a history of 39 years, Verhoeff Society is one of the oldest subspecialty groups in ophthalmology. The society was formed to establish a forum to discuss ophthalmic pathology. This paper details the original inception of the Society, its current activities and its influence in the development of ophthalmic pathology clubs in the U.S. and across the world.

Ocular signs in thiamine-deficient monkeys and in Wernicke's disease in humans.

Thiamine deficiency in the monkey is the animal counterpart of Wernicke's disease in humans. In the present study, thiamine deficiency was induced in 11 monkeys while three monkeys were given paired feedings supplemented by thiamine hydrochloride and three monkeys were maintained on regular chow. The typical clinical symptoms were apathy, inattention to peripheral stimuli, ataxia, ptosis, mydriasis progressing to pupillary areflexia, nystagmus, and ophthalmoparesis progressing to total ophthalmoplegia. With thiamine treatment, recovery was prompt and complete in mild to moderate cases but delayed and incomplete in severe cases. The animals were killed six or more months after discontinuance of the experiments to determine the chronic effects of treated thiamine deficiency. The significant abnormalities in the brain stem were symmetric gliosis and neuronal loss in the inferior colliculi, the regions of the third and sixth nerve nuclei, and the medial vestibular nuclei. White matter was characteristically spared. With the exception of the inferior colliculi, the target sites for neuropathologic changes were the centers for ocular motor control.

Visual disturbances with focal progressive dementing disease.

Symptoms referable to the visual system may be the earliest and most prominent signs of idiopathic dementing disease (Alzheimer's type) despite the lack of objective signs in the eyes or visual system. Three such patients are described. The first patient, who had ultimately proven Alzheimer's disease, initially complained of poor vision and spatial disorientation. Her course was characterized by progressive topographic agnosia during a ten-year period. The second patient first sought ophthalmic consultation for blurring of vision that subsequently progressed during a six-year period to alexia without agraphia and spatial disorientation. The third patient, who had presumed Alzheimer's disease, initially complained of reading difficulties that prompted several ophthalmic consultations. Her problem was initially one of increasing visual agnosia which, together with other perceptive disturbances, gradually deepened during a period of several years.