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Action of thymoxamine on mydriasis induced by levodopa and dopamine.

Eye-drops of levodopa and dopamine induce pupillary dilatation which is inhibited by thymoxamine, an alpha-adrenergic blocking drug. This indicates that the mydriatic action of levodopa and dopamine involves excitation of alpha-adrenergic receptors of the dilator pupillae muscle. Such a conclusion is in accord with the previously expressed suggestion that levodopa is rapidly converted to dopamine, which displaces noradrenaline from adrenergic nerve endings.The findings that dopamine exerts alpha-adrenergic effects at the periphery may be construed as evidence in support of the view that the hypotensive action of levodopa is mediated via the central nervous system.

Adrenergic alpha-Antagonists↗

An unusual uveitis in Tanzanian children.

In 1982-7, 254 children with panuveitis were seen at Mvumi Hospital, Tanzania, representing 56% of all cases of uveitis seen. Half were aged under 2. No consistent abnormality accounted for the uveitis and it resolved spontaneously over 6-12 weeks. A trial of prednisolone was performed in 30 children: 18 showed improvement by four weeks compared with 20 of 35 controls given only topical steroids and mydriatics.

Child↗

Use of mobile screening unit for diabetic retinopathy in rural and urban areas.

OBJECTIVES: To compare the effectiveness of a mobile screening unit with a non-mydriatic polaroid camera in detecting diabetic retinopathy in rural and urban areas. To estimate the cost of the service. DESIGN: Prospective data collection over two years of screening for diabetic retinopathy throughout Tayside. SETTING: Tayside region, population 390,000, area 7770 km2. SUBJECTS: 961 patients in rural areas and 1225 in urban areas who presented for screening. MAIN OUTCOME MEASURES: Presence of diabetic retinopathy, need for laser photocoagulation, age, duration of diabetes, and diabetic treatment. RESULTS: Compared with diabetic patients in urban areas, those in rural areas were less likely to attend a hospital based diabetic clinic (46% (442) v 86% (1054), p < 0.001); less likely to be receiving insulin (260 (27%) v 416 (34%), p < 0.001 and also after correction for differences in age distribution); more likely to have advanced (maculopathy or proliferative retinopathy) diabetic retinopathy (13% (122) v 7% (89), p < 0.001); and more likely to require urgent laser photocoagulation for previously unrecognised retinopathy (1.4% (13) v 0.5% (6), p < 0.02). The screening programme cost 10 pounds per patient screened and 1000 pounds per patient requiring laser treatment. CONCLUSION: The mobile diabetic eye screening programme detected a greater prevalence of advanced retinopathy in diabetic patients living in rural areas. Patients in rural areas were also more likely to need urgent laser photocoagulation. Present screening procedures seem to be less effective in rural areas and rural patients may benefit more from mobile screening units than urban patients.

Diabetic Retinopathy↗

Action of dopamine on the human iris.

Dopamine eye drops produce marked dilatation of the pupil in man. This mydriatic effect is inhibited by pretreatment with guanethidine. It is therefore concluded that dopamine acts indirectly via adrenergic nerve endings, rather than exerting a direct effect on adrenergic receptors in the dilator pupillae muscle. In this respect dopamine resembles the phenyl-alkylamines, such as tyramine, rather than the catecholamines, adrenaline and noradrenaline.If dopamine acts by releasing noradrenaline from adrenergic nerve endings, high concentrations of dopamine could lead to depletion of noradrenaline stores, since synthesis might be unable to keep pace with release. This could be the explantion for the orthostatic hypotension found in patients taking L-dopa for Parkinsonism.

Adult↗

Impact of diabetic retinopathy screening on a British district population: case detection and blindness prevention in an evidence-based model.

OBJECTIVES: To quantify case detection and blindness prevention attainable through screening for diabetic retinopathy in a district population. DESIGN: Literature review including a pooled estimate of screening test sensitivity, and quantitative modelling, including sensitivity analyses. SETTING AND PATIENTS: The diabetic population of a typical district health authority or health board. MAIN RESULTS: Evidence suggests that in a British general practice based diabetic population, prevalence of retinopathy requiring treatment would be between 1% and 6%; annual incidence of blindness among diabetics with retinopathy requiring treatment would be between 6% and 9%; sensitivity of screening tests in detecting retinopathy requiring treatment would be between 50% and 88%; and treatment could prevent 77% of expected cases of blindness. Of those screened, about 4% would be correctly detected as requiring treatment during an initial screening round, but this yield could decrease to about 1% in subsequent annual screening rounds. Of those treated, about 6% would be prevented from going blind within a year of treatment and 34% within 10 years of treatment. CONCLUSIONS: Screening and early treatment of diabetic retinopathy can prevent substantial disability. The effectiveness and efficiency of screening could be enhanced by improving the performance of current tests or increasing use of mydriatic retinal photography, and by increasing uptake, particularly among diabetics at greatest risk.

Blindness↗

Generalised anhidrosis: different lesion sites demonstrated by microneurography and skin biopsy.

Generalised anhidrosis (GA) shows a uniform clinical picture whether the pathogenesis involves intrinsic abnormalities of sweat glands or postganglionic sympathetic cholinergic nerve dysfunction. We describe two patients who presented intolerance to heat and anhidrosis. In the first patient, symptoms started at 33 years of age, and were associated with absent tendon reflexes and a mydriatic right pupil unreactive to light. The other patient had been unable to sweat since birth. GA was diagnosed on the basis of clinical findings and thermoregulatory tests. Microneurography and morphological analysis of the skin and its innervation disclosed a different lesion site underlying GA in the two patients, and distinguished between a postganglionic autonomic nerve fibre lesion and sweat gland dysfunction.

Adult↗

People with Down's syndrome can be distinguished on the basis of cholinergic dysfunction.

The mydriatic response to eyedrops of the anticholinergic agent tropicamide at very low concentration (0.01%) has been studied in people with Down's syndrome. By comparison with healthy subjects people with Down's syndrome had responses approximately three times greater, suggesting a peripheral imbalance between cholinergic and adrenergic autonomic influences.

Adolescent↗

Pholedrine: a substitute for hydroxyamphetamine as a diagnostic eyedrop test in Horner's syndrome.

Mydriatic responses to eyedrops containing the indirect acting sympathomimetic amines tyramine, hydroxyamphetamine, and pholedrine have been compared in 10 healthy subjects. Pholedrine, the n-methyl derivative of hydroxyamphetamine, at a concentration of 1% had effects similar to those produced by 0.5% hydroxyamphetamine itself. Pretreatment with topical guanethidine attenuated its responses and in 13 patients with unilateral Horner's syndrome it distinguished clearly those five patients who had preganglionic from the eight with postganglionic lesions. It is concluded that 1% pholedrine may be substituted for 0.5% hydroxyamphetamine, which is no longer available, as a diagnostic agent for use in Horner's syndrome.

Adolescent↗

Uveitis associated with rifabutin and macrolide therapy for Mycobacterium avium intracellulare infection in AIDS patients.

OBJECTIVE: Uveitis has been increasingly recognised as a side effect of rifabutin regimens in the prophylaxis and treatment of Mycobacterium avium intracellulare (MAI) infection. This study describes the clinical features and analyses the factors associated with rifabutin induced uveitis. DESIGN: Retrospective observational study. SETTING: Tertiary care institution, The Royal Hospitals NHS Trust, London. PATIENTS: 68 HIV seropositive individuals receiving rifabutin for prophylaxis or treatment of MAI infection. RESULTS: 11 episodes of uveitis occurred in 10 different individuals at a median of 62 days. The disease was bilateral in four and unilateral in the remainder. All subjects experienced ocular pain and photophobia and 9 individuals had a significant reduction in visual acuity. Uveitis was treated with mydriatics and topical steroids and resolved in all cases when rifabutin was stopped. The risk of uveitis was significantly increased with concurrent clarithromycin therapy, Odds Ratio 13.08, 95% Confidence Interval 1.98 to 83.12. CONCLUSION: Rifabutin can cause a reversible uveitis. This risk is increased with concurrent clarithromycin therapy. Adverse drug interactions can be an important cause of morbidity in patients with advanced HIV disease.

AIDS-Related Opportunistic Infections↗

Iris movement mediates vascular apoptosis during rat pupillary membrane regression.

In the course of mammalian lens development, a transient capillary meshwork known as the pupillary membrane (PM) forms, which is located at the pupil area; the PM nourishes the anterior surface of the lens and then regresses to make the optical path clear. Although the involvement of apoptotic process has been reported in the PM regression, the initiating factor remains unknown. We initially found that regression of the PM coincided with the development of iris motility, and iris movement caused cessation and resumption of blood flow within the PM. Therefore, we investigated whether the development of the iris's ability to constrict and dilate functions as an essential signal that induces apoptosis in the PM. Continuous inhibition of iris movement with mydriatic agents from postnatal day 7 to day 12 suppressed apoptosis of the PM and migration of macrophage toward the PM, and resulted in the persistence of PM in rats. The distribution of apoptotic cells in the regressing PM was diffuse and showed no apparent localization. These results indicated that iris movement induced regression of the PM by changing the blood flow within it. This study suggests the importance of the physiological interactions between tissues-in this case, the iris and the PM-as a signal to advance vascular regression during organ development, and defines a novel function of the iris during ocular development in addition to the well-known function, that is, optimization of light transmission into the eye.

Animals↗

[Drowning in pediatric patients].

OBJECTIVE: Immersion accidents are still an important cause of morbidity and mortality in children. We performed a retrospective study to identify the prognostic factors associated with outcome in children who experience near-drowning, which could serve to guide decision-making. Our data were compared with other published data. PATIENTS AND METHODS: The medical records of children treated for near-drowning in our hospital from January 1995 to April 2003 were reviewed. The data analyzed referred to the patient, the accident, the patient's clinical status in the emergency unit, the unit to which the patient was admitted, and outcome. RESULTS: Sixty-two patients were included. Of these, outcome was bad in 12 (death in seven and irreversible sequelae in five). Statistically significant predictors of bad prognosis were age > or = 4 years, female sex, immersion time > or = 5 min, cyanosis in the emergency room, cardiac arrest, apnea or severe distress, hypothermia (core temperature < 35 degrees C), metabolic acidosis (pH < or = 7.10) and neurologic damage (Glasgow coma Scale score 3; Conn C; nonreactive and mydriatic pupils) on arrival at the hospital. CONCLUSIONS: Outcome is closely related to the patient's clinical status on arrival at the hospital. Although data that can serve as a guide to the final outcome of the nearly-drowned patient are available, early models to predict the final clinical results of each case, which could be used to guide initial resuscitation and subsequent treatment, are lacking.

Child, Preschool↗

Light scattering in normal and cataractous lenses of farmed Atlantic salmon (Salmo salar): a slit lamp and Scheimpflug photographic study.

To investigate normal light scattering and cataract formation, the anterior eye segments of farmed Atlantic salmon (Salmo salar) reared in fresh water and sea water were documented in vivo for the first time with a Topcon SL-45 Scheimpflug camera. A total of 40 fish from the fresh-water-rearing period, obtained from 2 groups of identical age but showing a different growth rate, and 24 fish from the sea-water-rearing period, sampled from 2 groups with identical age but being fed different food brands, were included in this study. The fish were anaesthetized before examination. Due to the naturally wide pupil, no mydriatic compound was applied. All fish were removed from the water for photography, which was performed for each eye in 0 degrees = vertical slit position. Images were recorded on Kodak Tmax 400 black-and-white film. Microdensitometric image analysis of all negatives was performed using a Joyce-Loebl online microdensitometer. In spite of the virtual absence of an anterior chamber gap between cornea and lens and very little light scattering in the normal fish lens, a small number of distinct layers could be reproducibly identified in the lens. While there was little abnormal light scattering which could point to cataract development in young fish from the fresh water period, the evaluation of the lenses from the 2 sea water groups showed the presence of specific forms of cataract especially in the cortical and supranuclear layers. There were significant differences between the groups fed different food brands at the sea water site. In conclusion, Scheimpflug photography proved to be applicable to eye research in fish in vivo. It is suggested that this method should be employed for reproducible documentation as an extension to slit lamp monitoring in experimental research to reveal causative factors for cataracts in farmed fish.

Animals↗

Corneal toxicity of xylazine and clonidine, in combination with ketamine, in the rat.

PURPOSE: To compare the corneal toxicity of xylazine (XYL)/ketamine (KET) with that of clonidine (CLO)/KET in the rat, in the presence or not of the alpha(2)-adrenergic antagonist yohimbine (YOH). METHODS: XYL (10 mg/kg) and CLO (0.15 mg/kg) were administered subcutaneously in the rat in combination with KET (50 mg/kg), in the presence or not of YOH (2 mg/kg). RESULTS: The corneas immediately lost transparency and luster, but recovered within 120 min. By both light and electron microscopy, a marked stromal edema and alterations of all layers were observed. In addition, XYL/KET altered the permeability of the cornea as indicated by the augmented levels of (14)C-indomethacin, topically administered 30 min after the anesthetic combination. CONCLUSIONS: The mechanism of the corneal toxicity of XYL and CLO in the rat is unclear but we speculate that: (a) proptosis and inhibition of normal blinking did not play a major role because topical application of hyaluronic acid did not protect against it; corneal decompensation, edema and opacification could be due to (b) osmotic or (c) mechanical endothelial stress: the first resulting from the sudden increase of the glucose concentration in the aqueous humor due to the well-known inhibition of insulin release by alpha(2)-adrenergic agonists, and the second from the acute elevation of intraocular pressure caused by these alpha(2)-adrenergic mydriatics in the rat; (d) addition, XYL and CLO could act by directly interacting with local alpha(2)- or, possibly, alpha(1)-adrenergic receptors, whose function is still not clear but probably essential for corneal homeostasis.

Adrenergic alpha-Agonists↗

Experimental evidence for interactive effects of chronic UV irradiation and nutritional deficiencies in the lens.

The eye lens is subjected to many risk factors over time, which contribute to changes in its transparency, finally leading in combination to cataract development. Ultra violet (UV) radiation is regarded as one of the widespread risk factors contributing to cataract formation, for example in combination with nutritional deficiencies. Both factors possibly contribute to the high number of cataracts in the sunbelt region of the world. In this study, two essential nutritional factors were investigated in Brown Norway rats, zinc and vitamin E deficiencies, alone and in combination with UV-A and UV-B irradiation. Young female Brown Norway rats were put on a special diet for 10 weeks, either highly deficient in Zinc or in vitamin E. The diet was otherwise identical to the control diet. Two weeks after putting the animals on the diet, UV irradiation was started in some of the groups with mydriatic pupils with 3 irradiation sessions per week (UV-A 1 J/cm2; UV-B 0.2 J/cm2). Irradiation was continued until the end of the diet treatment period. Body weight and food consumption were established at weekly intervals, as well as slitlamp microscopy to monitor changes in anterior eye segment morphology. In addition changes in transparency of the cornea and lens have been monitored and evaluated with a Scheimpflug camera (Topcon SL-45) at baseline, and after 4 and 8 weeks of irradiation. After sacrifice of the animals, the lens wet weight as well as the activity of superoxide dismutase (SOD) were determined. Zinc deficiency alone led to an almost complete arrest of body weight increase. In the cornea, UV-A in combination with zinc or vitamin E deficiency did not have any interactive effects. The combination of UV-B and zinc deficiency showed subtractive instead of additive effects on corneal transparency and neovascularization. In the lens both deficiencies positively interacted with UV-A and UV-B by increasing the density of the capsular and cortical layers. The lens fresh weight was significantly lower in zinc-deficient animals additionally irradiated with UV-A or UV-B. The activity of SOD was significantly lower in the lenses of zinc- or vitamin E-deficient animals additionally irradiated with UV-B. The experiments presented clearly demonstrate that dietary zinc and vitamin E deficiencies do interact with UV radiation damage in the cornea and lens of Brown Norway rats.

Animals↗

Investigation of the safety of an intraocular lens with reversibly adjustable optical power: the *Acri.Tec AR-1 PC/IOL.

PURPOSE: To report the safety of a newly developed intraocular lens (PC/IOL) with reversibly adjustable refractive power (*Acri.Tec AR-1 PC/IOL) after implantation into adult human eyes. The surgical setup and specially designed instruments required for implantation will be evaluated. The examined parameters included: stability of the IOL during implantation, positioning of the IOL, rotation of the IOL, integrity of the posterior lens capsule, central visual acuity, morphology of the eye, clinical signs of inflammation, intraocular pressure, refraction. METHODS: The study was carried out on 35 human eyes after using the Acri.Tec AR-1 PC/IOL after lens removal through phacoemulsification; as control, the implantation of conventional PC/IOL into the second eye of 29 patients was used. The mean follow-up was 9 + 6 months. An initial adjustment surgery of the *Acri.Tec AR-1 PC/IOL was carried out 2 weeks after implantation in 2 patients; the follow-up of these eyes was 3 and 6 months. RESULTS: Implantation was possible without any problem. Eyes healed normally. No difference between eyes containing the *Acri.Tec AR-1 PC/IOL and eyes containing conventional PC/IOLs could be detected with respect to visual acuity, stabilization of refractive error, signs of inflammatory reaction, slitlamp microscopic aspect of the eye and intraocular pressure. As intended, initial adjustment surgery successfully changed the mydriatic refraction from +1.0 resp. +0.75 dpt to 0 resp. -0.5 dpt. 26 bilaterally pseudophakic patients including 2 patients having had adjustment surgery had more than 3 months follow-up. Mean visual acuity in the AR-1 PC/IOL group at 3 months (0.76 +/-0.24) did not differ from mean visual acuity in the pseudophakic control group (0.74 +/-0.23). Adjusted eyes had a visual acuity of 1.0. No adverse effects occurred. CONCLUSION: Initial data suggest that the *Acri.Tec AR-1 PC/IOL can be safely implanted into the capsular bag of adult human eyes and can beadjusted after implantation, thereby achieving the desired change of refraction. Further exploration of the potential usefulness of this type of reversibly adjustable PC/IOL as a tool for refractive optimization is warranted.

Aged↗

Acetylcholine and alpha 1-adrenergic sensitivity in the separation of depression and anxiety.

Three relatively clear-cut diagnostic groups, namely primary major depressive disorder-endogenous subtype (PRI MDD-E), primary anxiety disorder with no depression (PRI ANX), and normal controls as well as two additional patient groups with mixed or coexisting anxious/depressive diagnoses were studied. Clinical assessment was made by routine psychiatric interview, Schedule of Affective Disorder and Schizophrenia (SADS) research interview, and obtaining family history of MDD. Subjects underwent both routine 'baseline' sleep EEG polygraphic arecoline, a muscarinic, cholinergic agonist infused during sleep. Cholinergic sensitivity was assessed by measuring the time to induction of REM sleep after arecoline infusion. In addition, a subgroup of MDD patients underwent pupillographic testing. Peripheral alpha-adrenergic responsivity was measured by the magnitude of pupillary mydriatic response after local ocular instillation of phenylephrine. Successful separation (83% correct classification) of the 'pure' groups (PRI MDD-E, PRI ANX, and normal) was achieved by discriminant function analysis of sleep EEG variables. Compared to PRI ANX and normal groups, patients with PRI MDD-E had supersensitive cholinergic REM-induction response, shorter REM latency, increased first REM density and REM percent. Separation of the PRI ANX and normal groups was by intermittent awake time, delta sleep percent, and total REM density. Classification of the mixed anxious/depressive groups was next attempted using the discriminant coefficients derived from the above analysis of 'pure' groups. We found that the presence of absence of family history of MDD in patients with mixed diagnosis offered the best prediction of classification into PRI MDD-E and PRI ANX groups, respectively. MDD patients with coexisting panic disorder were significantly subsensitive to phenylephrine-induced mydriasis compared to MDD patients without anxiety.

Acetylcholine↗

Automated detection of diabetic retinopathy in a fundus photographic screening population.

PURPOSE: To evaluate the performance of an automated fundus photographic image-analysis algorithm in high-sensitivity and/or high-specificity segregation of patients with diabetes with untreated diabetic retinopathy from those without retinopathy. METHODS: This was a retrospective cross-sectional study of 260 consecutive nonphotocoagulated eyes in 137 diabetic patients attending routine photographic retinopathy screening. Mydriatic 60 degrees fundus photography on 35-mm color transparency film was used, with a single fovea-centered field. Routine grading was based on visual examination of slide-mounted transparencies. Reference grading was performed with specific emphasis on achieving high sensitivity. Computer-assisted automated red lesion detection was performed on digitized transparencies. RESULTS: When applied in a screening population comprising patients with diabetes with untreated diabetic retinopathy in any eye and patients with diabetes without retinopathy, the automated lesion detection correctly identified 90.1% of patients with retinopathy and 81.3% of patients without retinopathy. A per-eye analysis for methodological purposes demonstrated that the automated lesion detection could be adapted to simulate various visual evaluation strategies. When adapted at high sensitivity, the automated system demonstrated sensitivity at 93.1% and specificity at 71.6%. When adapted at high specificity the automated system demonstrated sensitivity at 76.4% and specificity at 96.6%, closely matching routine visual grading at sensitivity 76.4% and specificity 98.3%. CONCLUSIONS: Automated detection of untreated diabetic retinopathy in fundus photographs from a screening population of patients with diabetes can be made with adjustable priority settings, emphasizing high-sensitivity identification of diabetic retinopathy or high-specificity identification of absence of retinopathy, covering opposing extremes of visual evaluation strategies demonstrated by human observers.

Aneurysm↗

Ocular complications in juvenile chronic arthritis (JCA).

Fifty-six children with JCA have attended the Rheumatology Clinic at the Royal Hospital for Sick Children, Glasgow, over the past five years. Eleven have monoarthritis, 21 pauciarthritis and 24 polyarthritis. Seven children with pauciarthritis and one with monoarthritis developed ocular complications. Of these six were girls. In six children the arthritis preceded the uveitis. In one child arthritis and uveitis presented at the same time and in another the uveitis preceded the arthritis by one year. All were treated with steroids (7 topically, 1 systemically) and topical mydriatic agents. After an initial response the uveitis persisted as a low-grade inflammation gradually leading to secondary complications and increasing loss of vision. Only two patients enjoy normal vision at present. The importance of routine slit-lamp microscopy in all children with JCA is stressed, especially in those with pauciarthritis and antinuclear antibodies.

Acute Disease↗