[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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