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[Antioxidants for prophylaxis of eye
diseases]
Kaluzny J
Kliniki Okulistycznej AM w Bydgoszczy.
Klin Oczna (Poland) Feb 1996, 98 (2) p141-3
The contemporary literature has widely described the role
of free oxygen radicals and their antioxidants in pathogenesis
of some eye diseases, mainly cataract, age-related macular
degeneration, retinopathy of prematurity and cystic macular
oedema. This paper presents publications which stress the
importance of antioxidants use in prophylaxis of cataract and
age-related macular degeneration. Positive antioxidants role
was proved both in experimental research and in clinical
observations. (29 Refs.)
A prospective study of cigarette smoking and
age-related macular degeneration in women
Seddon JM, Willett WC, Speizer FE, Hankinson SE
Epidemiology Unit, Massachusetts Eye and Ear Infirmary,
Boston, MA 02114, USA.
Journal of the American Medical Association (USA), 1996,
276/14 (1141-1146)
Objective. - To evaluate the relationship between cigarette
smoking and incidence of age-related macular degeneration
(AMD) among women.
Design. - Prospective cohort study with 12 years of
follow-up (1980 to 1992), in which information on smoking
habits was updated every 2 years.
Setting. - Eleven states throughout the United States.
Participants. - A total of 31 843 registered nurses
enrolled in the Nurses' Health Study who were aged 50 to 59
years in 1980 and did not report a diagnosis of cancer or AMD
at the beginning of the study. Additional women entered the
analytic cohort as they reached 50 years of age.
Main Outcome Measure. - Incidence of AMD with visual
loss.
Results. - During 556 338 person-years of follow-up, 215
women were newly diagnosed as having AMD. After adjusting for
other risk factors for AMD, women who currently smoked 25 or
more cigarettes per day had a relative risk (RR) of AMD of 2.4
(95% confidence interval (CI), 1.4-4.0) compared with women
who never smoked. Past smokers of this amount also had a
2-fold increased risk (RR=2.0; 95% CI, 1.2-3.4) relative to
never smokers. Compared with current smokers, little reduction
in risk was suggested even after quitting smoking for 15 or
more years. Risk of AMD also increased with an increasing
number of pack-years smoked (P for trend <.001); among
women who smoked for 65 or more peck-years, the risk was 2.4
times the risk of never smokers (95% CI, 1.5-3.8). Analyses of
dry and exudative types of AMD and other alternative
definitions of AMD revealed similar results.
Conclusions. - Cigarette smoking is an independent and
avoidable risk factor for AMD among women. Because AMD is the
most common cause of severe visual impairment among the
elderly and treatment is not available or is ineffective for
most patients, reducing the risk of this disease is another
important reason to avoid smoking.
Multicenter ophthalmic and nutritional age-related
macular degeneration study-part 1: design, subjects and
procedures.
Richer S
Eye Clinic 112e, DVA Medical Center, North Chicago, IL 60064,
USA.
J Am Optom Assoc (United States) Jan 1996, 67 (1)
p12-29
BACKGROUND: A prospective 18 month, double-blind
case-controlled study was designed to determine whether a
specific over-the-counter multivitamin/mineral/antioxidant
nutrient capsule taken twice daily prevents the progression
of, or improves the outcome of non-exudative ARMD. Two
randomly assigned experimental ARMD groups are compared to
each other, to age matched ARMD-free case controls and to 1994
NHANES III nutritional data.
METHODS: Thirty-two dry ARMD patients assigned to group one
(placebo) and 39 dry ARMD patients were assigned to group two
(Ocuguard, a broad spectrum antioxidant capsule). A third age
and sex matched ARMD-free case control group of 13 patients
who met the same entrance criteria were also selected. All
participants underwent thorough visual and nutritional
evaluation prior to initiation of the study. Both ophthalmic
tests and dietetic assessments were also performed at 6, 12
and 18 months following a 2-week initiation period.
RESULTS: In comparison to NHANES-III age stratified
population data and the Recommended Daily Allowance (but not
case controls), the ARMD population manifested decreased
intake of nutrients vital to cardiovascular health: vitamin E,
magnesium, zinc, vitamin B6 and folic acid. The two randomly
assigned experimental groups were well matched, with little
difference in baseline demographic, ocular, hematologic and
pre-intervention symptoms. There were differences in
nutritional intake between the two groups, due primarily to
significantly higher percent ideal body weight in group
two.
Multicenter ophthalmic and nutritional age-related
macular degeneration study--part 2: antioxidant intervention
and conclusions.
Richer S
Eye Clinic 112e, DVA Medical Center, North Chicago, IL 60064,
USA.
J Am Optom Assoc (United States) Jan 1996, 67 (1)
p30-49
BACKGROUND: The experimental design, subjects, procedures
and baseline data for the prospective double blind dry
ARMD-antioxidant intervention study have been described in
Part 1.
METHODS: At eight DVA medical centers, 32 patients (group
one) were assigned a placebo and 39 patients (group two) a
"broad spectrum" antioxidant capsule. Data was collected in
five areas: demographic; ophthalmic; dietary analysis of daily
food intake; serum analysis; and adverse gastrointestinal
symptoms. Data was serially acquired at baseline, 6 months, 12
months and 18 months, and was analyzed by univariate repeated
factors ANOVA, p = 0.05.
RESULTS: Group two (antioxidant po BID) maintained their
distance LogMAR visual acuity (p = 0.03), while there was a
trend toward both stabilized near M print (p = 0.07) and 6
cycle/degree contrast sensitivity (p approximately 0.10), in
left eyes. However, group two (antioxidant) also had increased
cortical opacification of the right lens (p = 0.04), compared
to group one (placebo). Self perceived stabilization of vision
was reported by subjects in group two and supported the
objective data (Pearson chi square; p = 0.05).
CONCLUSIONS: A specific 14 component antioxidant capsule
taken twice daily stabilized but did not improve dry ARMD
over the study period of 1.5 years. The ARMD stabilized eyes
had less advanced disease functionally but not by fundus
appearance. Decreased intake of cardioprotective nutrients
(vitamin E, zinc, magnesium, B6 and folate) in ARMD patients
remained constant over the course of the trial.
Radial distribution of tocopherols in rhesus monkey
retina and retinal pigment epithelium-choroid.
Crabtree DV, Adler AJ, Snodderly DM
Schepens Eye Research Institute, Harvard Medical School,
Boston, MA 02114, USA.
Invest Ophthalmol Vis Sci (United States) Jan 1996, 37 (1)
p61-76
PURPOSE. To map vitamin E as a function of distance from
the foveal center in the primate retina and retinal pigment
epithelium (RPE)-choroid.
METHODS. Eyecups from rhesus monkeys were dissected with
circular trephines so that the innermost disc, centered on the
fovea, was in the center of a series of concentric rings. Two
different types of dissection were performed. For one type,
the authors used circular trephines with diameters of 1, 4, 8,
and 10 mm (1,4-D), whereas for the other type the diameters
were 2, 5, 8, and sometimes 10 mm (2,5-D). When possible, the
neural retina was separated from the RPE-choroid. Tissues were
analyzed for vitamin E, retinyl palmitate, and protein.
RESULTS. Surface area, volume, and protein were used as
indexes of the amount of tissue analyzed. Distributions of
vitamin E in neural retina were dependent on the tissue metric
used and type of dissection performed. However, regardless of
the tissue metric used, the central 1-mm disc of the 1,4-D
was, on average, higher in vitamin E content than was the
central 2-mm disc of the 2,5-D. This was particularly true
when volume was the tissue metric. From the average values of
vitamin E in a series of concentric discs, a composite plot of
the vitamin E concentration in the neural retina was generated
that took into consideration both types of dissection. That
plot displayed a local maximum in the fovea and then
precipitously declined to a minimum in the region between 0.5
and 1.0 mm eccentricity (near the foveal crest); at greater
eccentricities, the vitamin E concentration rose to a value
similar to that in the fovea, i.e., the composite plot
indicated that vitamin E has a V-shaped distribution in the
central neural retina. Vitamin E distribution in the
RPE-choroid, with surface area as the tissue metric, also was
measured. For this tissue, the foveal region displayed a local
maximum.
CONCLUSIONS. By combining the results of two different
types of dissection, the authors found that in the neural
retina, vitamin E displayed a minimum near the foveal crest.
This minimum correlated //anatomically with the site at which
areolar (geographic) atrophy frequently occurs in retinal
pigment epithelial cells in the human disease, age-related
macular degeneration.
Treatment of senile macular degeneration with
Ginkgo biloba extract. A preliminary double-blind, drug versus
placebo study
Lebuisson D.A.; Leroy L.; Rigal G.
Centre Medico-Chirurgical Foch, F 92151 Suresnes Cedex
France
Presse Med. (France), 1986, 15/31 (1556-1558)
Senile macular degeneration is a frequent cause of
blindness for which there is no satisfactory medical
treatment. A double-blind trial comparing Ginkgo biloba
extract with placebo was conducted in 10 out-patients at the
Hopital Foch. Drug effectiveness was assessed on the results
of fundoscopy and of measurements of visual acuity and visual
field. In spite of the small population sample, a
statistically significant improvement in long distance visual
acuity was observed after treatment with Ginkgo biloba
extract. The assumed pathogenesis of senile macular
degeneration is discussed with emphasis on free oxygenated
radicals.
Hydergine - a new promise in neuro-retinal
disorders
Shukla M.
A.M.U. Institute of Ophthalmology, Aligarh, U.P. India
Afro-Asian J. Ophthalmol. (India), 1989, 8/1
(28-30)
Hydergine (co-dergocrine mesylate) was clinically evaluated
in 161 eyes of 96 patients suffering from different types of
neuro-retinal disorders which included various forms of optic
atrophy, retinitis pigmentosa, pathological myopia, dry senile
macular degeneration and heredomacular degeneration. While all
the patients received this treatment with tablets, 32
patients, in addition, received this therapy in injectable
form also. Beneficial results in terms of improvement in
visual acuity were noticed in 52 (32.30%) eyes after three
months of treatment. Long-term visual improvement or
stabilisation of visual acuity was seen in 40 eyes at 6 months
and 29 eyes between six months-one year respectively. The best
visual results were obtained in pathological myopia, anterior
ischaemic optic neuropathy, primary optic atrophy and typical
retinitis pigmentosa. While the initial results of Hydergine
treatment are quite encouraging in the treatment of certain
neuro-retinal disorders primarily with a neuronal transmission
defect and/or vascular ischaemic pathology, the cost factor is
a positive drawback particularly cases requiring long-term
treatment.
Inhibition of glutathione reductase by flavonoids.
A structure-activity study
Elliott A.J.; Scheiber S.A.; Thomas C.; Pardini R.S.
Department of Biochemistry, University of Nevada, Allie M.
Lee Lab. of Cancer Research, Mail Stop 330, Reno, NV 89557
USA
Biochem Pharmacol. 1992 Oct 20;44(8):1603-8.
A structure-activity study of fourteen chemically related
flavonoids was conducted to evaluate their abilities to
inhibit glutathione reductase (GR). By comparing the I50
values of flavonoids from different classes possessing an
identical hydroxyl configuration, we determined the following
order of potency for inhibition of GR: anthocyanidin >
dihydroflavonol = chalcone > flavonol > catechin. Enzyme
inhibition by delphinidin chloride and myricetin was partially
prevented in a N2 atmosphere which implicates a role for
oxygen in the mechanism of inhibition. To determine the role
of oxygen species in enzyme inhibition, GR was preincubated
with either mannitol, diethylenetriaminepenta-acetic acid
(DETAPAC), superoxide dismutase (SOD), catalase (CAT), or SOD
and CAT prior to assays for enzyme inhibition by flavonoids.
Enzyme inhibition by delphinidin chloride and myricetin was
suppressed by the addition of SOD, suggesting that superoxide
(O2.-) is involved. However, inhibition by quercetin and morin
was not sensitive to antioxidants. To further investigate the
role of O2.- in GR inhibition, a superoxide generating system
was utilized in the presence and absence of flavonoid. The
O2.- generating system failed to inhibit GR in the absence of
flavonoid but enhanced the inhibition by myricetin, indicating
that the O2.- did not directly inhibit GR but reacted directly
with certain flavonoids to form a reactive intermediate which,
in turn, inhibited GR. These findings suggest that the
mechanism of inhibition of GR by flavonoids is complex and may
have oxygen-dependent and oxygen-independent components.
Flavonoids, a class of natural products of high
pharmacological potency
Havsteen B.
Biochem Pharmacol 1983 Apr 1;32(7):1141-8
A review has been presented of the biochemistry and
pharmacology of a class of natural products, the flavonoids.
These substances which are widely distributed in the plant
kingdom and present in considerable quantities in common food
products, spices and beverages have in a concentrated form
(Propolis) been used since ancient times by physicians and
laymen to treat a great variety of human diseases but they
have yet to pass the tests of modern, controlled, clinical
experimentation. An attempt has been made to present the
fundamental evidence from the basic biological sciences which
is required to stimulate the interest of the clinicians in
this new field. The few existing reports on the careful
pharmacodynamic, pharmacokinetic and clinical studies which
have been made have been summarized to provide a basis for a
full-scale investigation of the therapeutic potential of
flavonoids.
Results with anthocyanosides from Vaccinium
myrtillus equivalent to 25% of anthocyanidines in the
treatment of haemorrhagic diathesis due to defective primary
haemostasis
Piovella F.; Almasio P.; Ricetti M.M.; et al.
Ist. Clin. Med. I Adolfo Ferrata, Univ. Pavia Italy
Gazz. Med. Ital. (Italy), 1981, 140/10 (445-449)
No abstract.
Studies on vaccinium myrtillus anthocyanosides. I.
Vasoprotective and antiinflammatory activity
Lietti A.; Cristoni A.; Picci M.
Res. Lab. Inverni della Beffa, Milan Italy
Arzneimittelforschung 1976;26(5):829-32
A Vaccinium myrtillus anthocyanoside preparation
(equivalent to 25% anthocyanidin) demonstrated significant
vasoprotective and antioedema properties in experimental
animals. In rabbits, the skin capillary permeability increase,
due to chloroform, was reduced both after i.p. (25-100 mg/kg)
and oral administration (200-400 mg/kg) of anthocyanosides.
Their activity was more lasting in comparison to rutin or
mepyramine and this did not seem to be due to a specific
antagonism towards inflammatory process mediators such as
histamine or bradykinin. Experiments carried out in rats
demonstrated that Vaccinium myrtillus anthocyanosides were
effective both in skin permeability test and on vascular
resistance of rats fed a P factor deficient diet. In the
former test effective doses were in the range of 25-100 mg/kg
(by oral route). In both animal species investigated,
anthocyanosides were twice as active as the flavonoid rutin.
Vaccinium myrtillus anthocyanosides by oral route inhibited
carrageenin paw oedema in rats showing a dose response
relationship. An antioedema activity was detected also after
i.v. or topical application.
Atrophic macular degeneration. Rate of spread of
geographic atrophy and visual loss
Schatz H.; McDonald H.R.
Retina Research Fund of St. Mary's Hospital and Medical
Center, San Francisco, CA USA
Ophthalmology. 1989 Oct;96(10):1541-51.
The authors studied 50 eyes with atrophic (dry) macular
degeneration (geographic atrophy of age-related macular
degeneration (GAMD), in 50 consecutive patients for 2 to 6
years (average, 3.4 years). There were 35 women and 15 men
ranging in age from 60 to 89 years (average, 73 years). The
areas of atrophy tended to follow the disappearance or
flattening of soft drusen, pigment epithelial detachment, or
reticular mottling of the retinal pigment epithelium. The
atrophic areas were multifocal in 20 of the 50 eyes. Atrophy
of the retinal pigment epithelium was followed by atrophy of
the choriocapillaris. The atrophic areas tended to expand
(average rate in one direction, 139 microm per year) and cause
gradual loss of central visual acuity. The rate of significant
visual loss (from 20/50 or better to 20/100 or worse) was 8%
of eyes per year. There was a tendency toward resistance of
the spread of atrophy into the fovea. The atrophy tended to
expand faster in patients under age 75 and slower in patients
aged 75 and over. Subretinal neovascularization developed in
ten of the 50 eyes.
Study of aging macular degeneration in China
Wu LH
Zhongshan Ophthalmic Center, Sun Yat-sen University of
Medical Sciences, Guangzhou, China.
Jpn J Ophthalmol 1987;31(3):349-67
Studies of the epidemiology, pathogenetic factors and
visual function of aging macular degeneration (AMD) show that
it has become an ocular disease worth noticing in China.
Although most AMD cases were of the dry type and the patients
had rather good visual acuity, various determinations of
visual function showed different degrees of impairment.
Controlling light exposure and improving trace metal
metabolism may be helpful for early prevention and treatment
of AMD. It will also be an important factor in the prevention
of blindness in Asian nations.
Subretinal neovascularization in senile macular
degeneration
Berkow J.W.
Department of Ophthalmology, Greater Baltimore Medical
Center, Baltimore, MD
Am J Ophthalmol 1984 Feb;97(2):143-7
When fluorescein angiograms from 563 patients with senile
macular degeneration examined at a large community hospital
during a 9.5-year period were retrospectively reviewed, 200
patients were found to have a dry atrophic type of senile
macular degeneration, consisting of drusen and retinal pigment
epithelial changes. Of the 363 patients with exudative senile
macular degeneration, 244 had subretinal neovascular
membranes. Seventy-eight membranes were less than 1 disk
diameter in size. Most of the large (157 of 224) and small (44
of 78) membranes showed a predilection for the fovea. Only 13
large and six small neovascular membranes were 200 mum or more
from the center of the foveal avascular zone.
Delayed macular choriocapillary circulation in age
related macular
Zhao J.; Frambach D.A.; Lee P.P.; Lee M.; Lopez P.F.
Doheny Eye Institute, Department of Ophthalmology, Univ.
Southern California Sch. Med., 1450 San Pablo Street, Los
Angeles, CA 90033 USA
Int Ophthalmol 1995;19(1):1-12
Purpose. To investigate the macular choriocapillary
circulation (MCC) in eyes with age-related macular
degeneration (ARMD) and to correlate these findings with the
associated clinical and angiographic drusen
characteristics.
Methods. Scanning laser ophthalmoscope fluorescein
videoangiography was performed on 34 eyes with age-related
macular degeneration and eight age-matched normal volunteers.
Drusen characteristics were assessed using the Wisconsin
age-related maculopathy grading scale.
Results. A delayed macular choriocapillary circulation
(DMCC) was defined as a macular choriocapillary filling time
greater than 3 standard deviations from the normal mean
(greater than 5 seconds). Nine (26%) of the 34 eyes with ARMD
were found to have a DMCC. After age adjustment, eyes with
DMCC were more likely to have geographic atrophy of the
retinal pigment epithelium (p = 0.003) or choroidal
neovascularization p = 0.07) than were eyes with a normal MCC.
Regional differences in choriocapillary filling times were
present in the eyes with a DMCC, including nasal-to-temporal,
central-to-peripheral, and inferior-to-superior gradients of
progressively less choriocapillary filling delay. The DMCC
correlated with the location, number, size, confluence, and
fluorescein staining characteristics of the associated
drusen.
Conclusion. DMCC occurs in some eyes with ARMD. This
finding may not only assist in defining eyes at risk for
progressive disease but may also help to elucidate the
pathogenesis of age-related macular degeneration.
Cystoid macular degeneration in experimental branch
retinal vein occlusion
Wallow I.H.L.; Danis R.P.; Bindley C.; Neider M.
Department of Ophthalmology, University of Wisconsin School
of Medicine
Ophthalmology 1988 Oct;95(10):1371-9
Macular edema and collateral vessels were examined
clinically and histopathologically up to 48 months after
branch retinal vein occlusion in six eyes of five cynomolgus
monkeys. In all six, central macular swelling and fluorescein
leakage from the retinal vasculature were confined to the
acute stage. However, histopathologically, at the chronic
stage, only two maculas were completely recovered and
unremarkable, whereas the other four showed variable degrees
of cystoid degeneration and photoreceptor cell loss. In the
two recovered maculas, six to eight normal-sized capillaries
separated the fovea from the nearest cluster of capillary
collaterals. In three maculas with cystic degeneration,
collaterals incorporated the circumfoveal capillaries. In the
fourth macula with cystic degeneration, collaterals were
separated from the center by two normal-sized capillaries but
were also associated with large areas of capillary
nonperfusion partially due to occlusion of the macular
arteriole.
The clinical picture of retinal thrombosis
Niesel P.
Univ.-Augenklin., Bern Switzerland
Klin Monatsbl Augenheilkd 1977 Feb;170(2):186-92
Besides acute arterial occlusion and simple venous
thrombosis, the clinical symptomatology may include signs of
chronic arterial insufficiency, i.e. progressive blurring of
vision, absolute visual field defects, cotton wool exudates,
capillary occlusion and increased retinal circulation time.
The poor visual prognosis is caused by progressive macular
degeneration. In the case of acute arterial thrombosis,
fragmentation of the blood column and absence of arterial
pulsation are indicative of pronounced retinal ischemia. The
ophthalmoscopic aspect of a visible embolus may be a hint for
the prognosis of eventual recanalisation.
[Findings of fluorescence angiography studies of
the posterior eye pole]
Baurmann H.
Ber Zusammenkunft Dtsch Ophthalmol Ges
1975;(73):56-9
The main findings during fluorescence angiography of the
macular area are classified on the basis of topographic points
of view. Macular changes are schematically presented in 5
stages: vitreoretinal boundary area; puckering syndrome;
retinal circulation; perimacular capillary changes; sensory
epithelium; not visualized in the angiogram; pigment
epithelium and Bruch's membrane; central retinal detachment;
deposits in the macular area; macular degeneration, secondary
maculopathies; haemorrhages below the pigment epithelium;
disorders of the pigment epithelium; Bruch's membrane and
other levels (inflammations, scars, macular defects); choroid;
folds, scars, atrophies, tumors.
The evoked cortical potential in macular
degeneration
Orpin J.A.; Orpin E.; McCulloch C.
Dept. Ophthalmol., Univ. Toronto Canada
J Am Geriatr Soc 1974 Dec;22(12):536-7
Macular degeneration causes a profound loss of visual
acuity due to inadequate blood circulation in the capillaries
of the choroid plexus and pigment epithelium of the important
pattern recognizing area of the retina. This disease is the
cause of half the blindness in people over the age of 65, and
of nearly one third of all blindness. In this study, an
important new technique was added to 6 tests already in use,
to assess retinal disease. Data on 10 patients were collected
by the following methods: optic disc photography; fluorescein
angiography; visual acuity testing; visual fields; foveal
sensitivity; electroretinography with automatic analysis of
the record by use of an electronic sampling filter and a
specially built computer to measure the total electrochemical
energy released by the retina; and the evoked cortical
response (as indicated in the electroencephalogram) to the
stimulus of an alternating chess board pattern. This new
technique tests the total system for visual pattern
recognition. The results indicate that the evoked cortical
response is the best objective test of visual acuity.
The development of neovascularization of senile
disciform macular degeneration
Teeters V.W.; Bird A.C.
Inst. Ophthalmol., London United Kingdom
Am J Ophthalmol 1973 Jul;76(1):1-18
Ninety five eyes with senile disciform macular degeneration
were evaluated for the presence of neovascularization, using
biomicroscopy and fluorescein angiography. The disciform
lesions were classed as avascular, neovascular, and advanced
cicatricial. Four to 27 mth later these disciform lesions were
reassessed. At that time, 67% of the initially avascular
disciform lesions had developed new blood vessels in the
subpigment epithelial vessels and 12% of fellow eyes with
drusen and pigment epithelial changes had developed disciform
processes. The patterns of neovascularization observed on
follow up examination conformed to two general types: early
vascular patterns usually with a capillary plexus in the
submacular position, and advanced vascular patterns consisting
of large vessels seen with the biomicroscope supplying a
plexus of capillaries usually eccentric to the macula. In the
early lesions, the neovascular complexes demonstrated marked
growth, frequently with development of eccentric capillaries
and large vessels. Lesions initially with large vessels
demonstrated slower growth, and in general the large vessel
was considered a sign of maturity of the lesion. Treatment of
the neovascular disciform lesion should be directed to the
capillary plexus which is responsible for exudation and
bleeding with secondary detachment of the macula.
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