Octreotide, a somatostatin analogue, fails to inhibit hypoxia-induced retinal neovascularization in the neonatal rat.

OBJECTIVE: Octreotide, a somatostatin analogue, has been shown to prevent angiogenesis in diverse in vitro models. We evaluated its effect on retinal neovascularization in vivo, using a neonatal rat retinopathy model. METHODS: We used, on alternating days, hypoxia (10% O2) and hyperoxia (50% O2) during the first 14 days of neonatal rats, to induce retinal neovascularization. Half of the rats were injected subcutaneously with octreotide 0.7 microg/g BW twice daily. At day 18 the eyes were evaluated for the presence of epiretinal and vitreal hemorrhage, neovascularization and epiretinal proliferation. Octreotide pharmacokinetics and its effect on serum growth hormone (GH) and insulin-like growth factor I (IGF-I) were examined in 28 rats. RESULTS: Serum octreotide levels were 667 microg/l two hours after injection, 26.4 microg/l after nine hours and 3.2 microg/l after 14 hours. GH levels were decreased by 40% (p = 0.002) two hours after injection but thereafter returned to baseline. IGF-I levels were unchanged two hours after injection and were elevated by 26% 14 hours after injection (p = 0.02). Epiretinal membranes were highly associated with epiretinal hemorrhages (p < 0.001), while retinal neovascularization was notably associated with vitreal hemorrhages (p < 0.001). CONCLUSIONS: Twice-daily injections of octreotide failed to produce sustained decrease in serum GH, but produced rebound elevation of serum IGF-I. Accordingly, no statistically significant effect of injections on retinal pathology was noted. This finding, however, does not contradict our assumption that GH suppression may decrease the severity of retinopathy.

Gene expression of insulin-like growth factor-I, its receptor and binding proteins in retina under hypoxic conditions.

Hypoxia is the main stimulus for neovascularization in the retina. Insulin-like growth factor-I (IGF-I) is thought to be one of the mediators of this process. Severe persistent hypoxia, as occurs in central retinal artery occlusion, is associated with less retinal neovascularization than relative hypoxia. To study the influence of different types of hypoxia on the IGF system, we used a model of neonatal rat retina that responds with neovascularization to a relative hypoxic stimulus produced by alternating oxygen concentrations in the respired air. We studied the influence of 24-hour hypoxia (10% oxygen), 48-hour hyperoxia (75% oxygen), and relative hypoxia (shifting from 48 hours in 75% oxygen to 24 hours in room air) on the gene expression of IGF-I, IGF-I receptor (IGF-IR), and IGF binding protein-1 (IGFBP-1), IGFBP-2, and IGFBP-3 in retina using a solution hybridization RNase protection assay. Hypoxia induced a significant increase in retinal IGF-IR (178%), IGFBP-2 (227%), and IGFBP-3 (317%) mRNA; however, retinal IGF-I mRNA was reduced, as well as serum growth hormone (GH). Relative hypoxia caused a similar but less pronounced trend in the gene expression of IGF-IR and the binding proteins, whereas retinal IGF-I mRNA was unchanged and serum GH was elevated. Both hypoxia and relative hypoxia may cause IGF system stimulation in the retina through upregulation of IGF-IR and IGFBPs. This stimulation may result in neovascularization. However, during hypoxia, low levels of tissue oxygenation and reduced local production of IGF-I may impede the neovascularization process.

Electrophysiological studies on the effects on single cells of silver electrodes implanted in the visual cortex of cats.

We have studied whether the presence of an artificial metal conductor in the visual cortex has an effect on the responsiveness pattern of the cells there. The physiological properties of single cells have been characterized in the mammalian primary visual cortex, following the acute and chronic implantation of silver wire electrodes. The Experimental group was Chronic and Acute operated and implanted adult cats. The Control group consisted of operated, but not implanted, adult cats and intact (Normal) adult cats. A sagittal incision was unilaterally made in the primary visual cortex (area 17) and a silver wire was implanted. Single cells were extracellularly recorded in the pre- and postincision regions following anesthesia and paralysis, 4-8 weeks following the implantation in the Chronic and immediately in the Acute group. The responsiveness, ocular dominance, receptive field properties, orientation, and direction selectively of the cells were examined. The responsiveness level was different in the preincision (afferented) regions of all operated groups. I was consistently affected compared with their deafferented region. The main effect was found on the binocularity of cells in all operated groups. The following are the differences found between the preincision and postincision regions. Our findings show that although a metal wire conductor implanted in the mammalian visual cortex has an effect on the efficiency of the cells there, chemically inert metals may serve in the future as artificial conductors in the brain.

Histology of posterior scleral foramen in normal eyes: its possible role in optic nerve damage in chronic open angle glaucoma.

We examined the histologic features of the posterior scleral foramen in 27 enucleated eyes (16 during autopsy and 11 with choroidal malignant melanoma). The histologic findings of the posterior scleral foramen were similar to those in previous reports. The shape of the scleral foramen was either cylindrical or truncated, the latter occurring when the inner margin of the sclera projected with a crest-like edge pressing into the optic nerve. This configuration was encountered more frequently in the upper and lower temporal aspects of the scleral foramen in 10 eyes, while the nasal rim was free of such projection in all the eyes. We hypothesize that the effect of prolonged high intraocular pressure exerted on the axonal tissue against these crest-like edges of the non-distensible scleral foramen might be the major factor in the etiology of early arcuate nerve fiber bundle defects in primary open-angle glaucoma.

The Israeli ocular injuries study: incidence of legal blindness from ocular trauma.

A 3 year nationwide study of the incidence of hospitalized civilian ocular injuries was conducted in Israel between October 1981 and September 1984. Of the 2,276 hospitalized cases (2,416 eyes), 457 resulted in unilateral, and 6 in bilateral legal blindness. These figures represent an average annual incidence rate of legal blindness of 3.8/100,000 persons, which was highest among 6-17 year olds (4.9/100,000). Injuries sustained in road accidents were the most highly morbid, resulting in blindness in 34% of road accident victims. Sports injuries accounted for 5% of all injured eyes and led to blindness in 10% of the cases so injured. Blindness resulting from injury occurs among people of all ages, often leads to a lifelong disfiguring disability, and increases the risk of bilateral blindness. It is widely maintained that with proper education and adoption of proper safety standards, such injuries can be largely prevented.

[Prenatal diagnosis of albinism].

Prenatal diagnosis of oculocutaneous albinism (OCA) was made in 1 of 6 pregnancies at risk examined during the 20th week of gestation. A skin biopsy was taken from the fetal scalp under ultrasonic screening. Light and electron microscopy studies were performed in each case to demonstrate melanin pigment and melanosomal development in the melanocytes of the hair bulbs and the epidermis. In 1 fetus albinism was diagnosed by the absence of melanin pigment and by the demonstration that melanosomes were only present in stages I and II. In the other 5 fetuses melanin pigment and mature melanosomes (up to stage IV) were demonstrated. The pregnancy with the albino fetus was interrupted and the diagnosis of OCA was confirmed at autopsy.

Low-vision aids in Stargardt's disease.

Fifteen patients with juvenile macular degeneration fitted with low-vision aids were followed up for a period of two to three years. About 80% of the patients equipped with visual aids used their devices successfully. It appears that in Stargardt's disease, low-vision aids are more useful than in other maculopathies.

The Israeli Ocular Injuries Study. A nationwide collaborative study.

A nationwide study of patients hospitalized for ocular injuries was conducted in Israel during the years 1981 through 1983, with the participation of 17 ophthalmic departments. The study comprised 2276 patients (2416 eyes), 47% of whom were children. The male-female ratio was 4.3:1. Bilateral injuries occurred in 140 patients, with children sustaining the most severe injuries. Ocular injuries occurred most frequently at home, and children at play were most vulnerable. Most patients retained good vision, 3.7% lost vision totally, and 2% of the eyes had to be enucleated.

Zinc and copper metabolism in oculocutaneous albinism in the Caucasian.

Abnormalities in the zinc and copper metabolism have been described in some pigmentary retinopathies. In these eye disorders changes in the Retinal Pigment Epithelium are a common finding. Albinism is a manifestation of a metabolic disorder with abnormalities of pigment formation which also occurs in this mentioned retinal layer. Recently, we described abnormalities in the metabolism of these metals in black albino patients. In them, elevated values of ceruloplasmin were found. In the present study we performed a similar work among Caucasians. When both the Caucasian albino and control groups were compared, no statistical difference in the ceruloplasmin, serum zinc and copper and their concentration in urine was present. However, in 7 patients of the Caucasian albino group the serum zinc was distinctly elevated. The mean concentration of ceruloplasmin was high as well. No definitive correlation in regard to the positivity or negativity of tyrosinase was observed. Our findings may support our previous observations regarding albinism as a possible primary abnormality of zinc and copper metabolism.

Bilateral morning glory syndrome with midline brain lesion in an autistic child.

A ten-year-old autistic boy with high myopia and very poor vision presented a bilateral anomaly of the disc, diagnosed as morning glory syndrome. Further investigation showed an absence of the corpus callosum and probably herniation of an encephalocele into the third ventricle. The association of bilateral morning glory syndrome and very low visual acuity in both eyes with a midline brain lesion and autism has not been previously described.

Central retinal vein occlusions in young adults.

This study was a long term follow-up of 11 young adults aged 15-45 with central retinal vein occlusion (CRVO). Seven patients classified as the ischemic type of CRVO showed a poor visual acuity at the first examination and did not improve throughout the study. In addition, systemic diseases were found in all these patients. Four patients classified as venous stasis retinopathy type of CRVO, had, in contrast, fairly good visual acuity at the first examination and showed additional improvement during the follow-up period. No systemic diseases were detected. Physical examinations are recommended periodically for young adults with ischemic type of central retinal vein occlusion.

Female sex hormone and nephropathy in Cohen diabetic rat (genetically selected sucrose-fed).

In the Cohen diabetic rat (genetically-selected sucrose-fed) ovariectomy resulted in a significantly decreased incidence of nephropathy, while estradiol treatment to the ovariectomized animal increased the rate of nephropathy to the levels occurring in the uncastrated untreated diabetic female. In the male diabetic animal orchidectomy caused a slight decrease in the rate of nephropathy whereas estradiol treatment to the orchidectomized animal resulted in a slight increase in the rate. No difference was found between the ovariectomized and the uncastrated diabetic female as to the spontaneous blood glucose, plasma insulin, serum cholesterol or TG levels, but a significant difference was found in their plasma estradiol levels.

Prevalence and 15-year incidence of retinopathy and associated characteristics in middle-aged and elderly diabetic men.

We examined 178 men for the presence of diabetic retinopathy during 1978-80. They had been part of a group of 205 men from the Jerusalem area, diagnosed as being diabetic or having an abnormal glucose tolerance test in the Israel Ischaemic Heart Disease Project, a 5-year epidemiological investigation of Israeli male government employees. Seventy-four (42%) had diabetic retinopathy as determined by direct and indirect ophthalmoscopy, 3-mirror contact lens examination, and fundus photography. Those with and without retinopathy were compared for clinical, biochemical, behavioural, and biographical variables measured subsequently in 1963, 1965, and 1968. We found no significant differences between the 2 groups with respect to antecedent Quetelet index, blood pressure, peripheral vascular disease, blood lipids, haematocrits, smoking habits, area of birth, and education. Statistically significant differences between men with and without retinopathy were found for severity of carbohydrate metabolic intolerance at identification, duration of the metabolic abnormality, age, casual glucose values, and serum uric acid levels. Low serum uric acid appears to precede the incidence of diabetic retinopathy and to decline further as the disease progresses.

Control of blood glucose levels and development of diabetic microangiopathy: effect of glibornuride.

Genetically selected, sucrose-fed Cohen diabetic rats, aged 2 1/2 mo, were treated intragastrically with glibornuride, twice daily for 7 1/2 mo. The dose of 6 to 12.5 mg was adjusted according to the blood glucose level. Diabetic siblings with a similar metabolic derangement were used as a control group. Glibornuride treatment resulted in a significant reduction in blood glucose and an elevation in plasma insulin. A decreased incidence of diffuse glomerulosclerosis was noted in the treated group, in comparison with the control group (34.0 vs. 61.8%, P less than 0.02). The incidence of retinal lesions was also lower in the glibornuride-treated group (16.7 vs. 48.0%, P less than 0.02). Animals with diffuse glomerulosclerosis had significantly higher blood glucose and cholesterol levels and lower plasma insulin than did animals with normal kidneys.

Effects of experimental hyperlipoproteinaemia on the retina and optic nerve in rhesus monkeys.

Hyperlipoproteinaemia resulting from thyroid suppression and long-term ingestion of a high cholesterol diet caused prolonged lipaemia retinalis in 6 rhesus monkeys. No atherosclerotic deposits or other ophthalmoscopically visible changes of the retinal vasculature were detectable. In 2 animals histopathological examination revealed segmental atrophy and gliosis of the optic nerves bearing a resemblance to chronic ischaemic optic neuropathy. One monkey developed ophthalmoscopically visible temporal pallor of the optic discs. Emboli of fat laden cells in blood vessels of the brain in one of these 2 monkeys, and in a penicillated splenic artery in the other animal, were associated with signs of systemic embolic occlusion, suggesting a similar course in the development of optic nerve damage.

Cortical blindness in infancy: a follow-up study.

Clinical data of 6 cases of cortical blindness in infancy were analyzed. The underlying brain damage was a result of hypoxic events occurring in the pre- or perinatal period, or shortly after birth. The long-term follow-up of the children showed that some visual recovery occurred but capacity of recognition remained impaired. Early diagnosis of this entity and adequate education will help the visual and psychomotor development of the child.

Prevalence of trachoma among children in East Jerusalem in 1980.

In a ophthalmic survey conducted in East Jerusalem during 1980 comprising 8896 nursery and primary school children aged 3 to 12 years not a single case of active trachoma could be detected. A similar study carried out in 1968, encompassing the same geographical area, revealed a prevalence of 6.4% among the school children and of 12.5% among the nursery school infants, while a subsequent survey performed in 1971, including the same population age group, showed a sharp decrease in the incidence of trachoma to a level as low as l%. This gradual and continuous decline in the prevalence of the disease towards its end point of apparent eradication was preceded by a marked improvement in the socioeconomic status and personal and public hygiene of the general population.

Refractive power of premature children at infancy and early childhood.

We evaluated the refraction of 198 children born prematurely with birth-weights of 2,000 g or less, without any ocular disease. Between the ages of 6 months to 3 1/2 years these children had a mild hypermetropia. The refractive error did not change between the ages of 6 months and 3 1/2 years. The refraction of the prematurely born children was similar to that found in children born at full term.

Diabetic retinopathy in visual deprivation. A case report.

A case of asymmetric retinal involvement in a diabetic patient who has long been exposed to visual deprivation on one eye is described. The question implied by this condition is if a relationship could exist between the distinct exposure of each eye to different visual excitations, and the outcome of the different retinal diabetic involvement. The possibility that the retina in a resting state might be less prone to develop diabetic retinopathy than usual, and a possible functional hypothesis on the pathogenesis of this diabetic complication, are questioned.

Teratoid intraocular medulloepithelioma.

The right eye of a 1-year-old black infant with a painful blind eye was studied histologically. It contained a tumor at an advanced stage of growth. The tumor consisted of moderately large, round, and elongated undifferentiated cells and anaplastic cells with mitotic figures combined with multilayered, poorly differentiated epithelial cells that resembled the medullary epithelium of embryonic retina. Strap cells with cross striation typical of striated muscle were also present, together with islands of hyaline cartilage and areas of calcification.