|
Age-related macular degeneration : a review of
experimental treatments.
Ciulla TA; Danis RP; Harris A
Indiana University Macular Degeneration Clinic and Research
Center, Department of Ophthalmology, Indiana University School
of Medicine, Indianapolis, USA.
Surv Ophthalmol (Netherlands) Sep-Oct 1998, 43 (2)
p134-46
Age-related macular degeneration (AMD) is the leading cause
of irreversible visual loss in the USA. Laser photocoagulation
of choroidal neovascular membranes (CNVMs) in exudative AMD is
currently the only well-studied and widely accepted treatment
modality. It is beneficial for only a small minority of
patients who show well-demarcated "classic" CNVMs, and it
destroys normal retinal tissue, creates a scotoma, and is
associated with an unacceptably high CNVM persistence and
recurrence rate. Consequently, investigators have attempted to
develop new modalities for treatment of CNVMs. These treatment
modalities can be grouped into four major categories:
photodynamic therapy; pharmacologic inhibition of CNVM
formation with antiangiogenic agents; surgical intervention,
including excision of subfoveal CNVMs; and radiation therapy.
All of these experimental treatment modalities are directed
toward destroyiing CNVMs, the end result of the exudative
process, and all have limitations. The ideal treatment of the
future must be based on the pathogenesis of the disease at a
stage well before CNVMs develop. Investigations in
nonexudative AMD are currently focusing on several major
areas. Epidemiologic factors, such as genetics, sunlight, and
nutrition, are being evaluated in several large studies,
including the Age-Related Eye Disease Study, with the
possibility of ultimately limiting the risk of AMD through
behavior modification. Laser treatment of drusen is being
evaluated as a means of limiting the risk of CNVM formation,
although mixed results have been reported in the small number
of studies to date. Choroidal perfusion abnormalities have
been described in AMD, and some investigators postulate that
altering blood flow may limit the risk of CNVM formation. No
perfusion-treatment trials have been completed to date. (183
Refs.)
[Dynamics of accumulation and degradation of
lipofuscin in retinal pigment epithelium in senile macular
degeneration]
von Ruckmann A; Schmidt KG; Fitzke FW; Bird AC; Jacobi
KW
Institute of Ophthalmology, Universitats-Augenklinik,
Giessen.
Klin Monatsbl Augenheilkd (Germany) Jul 1998, 213 (1)
p32-7
BACKGROUND: It is thought that lipofuscin plays a central
role in the pathogenesis of age-related macular degeneration
(AMD). The lack of histopathological material has been a
severe limitation in our knowledge on lipofuscin in this
disease. A new technique has been developed that allows in
vivo imaging of fundus autofluorescence derived from
lipofuscin in the retinal pigment epithelium (RPE) using a
confocal Laser Scanning Ophthalmoscope (LSO). We studied the
dynamics of lipofuscin accumulation and degradation in
patients with AMD.
MATERIALS AND METHODS: Serial examinations of the spatial
distribution of fundus autofluorescence were performed in 148
eyes of 74 patients with AMD using a LSO over a period of
1-3.5 years.
RESULTS: Fundus autofluorescence changed over time in
almost all eyes studied. Areas of increased autofluorescence
occurred progressively during follow up in eyes with drusen
and hyperpigmentation. The size of pathologic autofluorescence
increased over time in almost all eyes with geographic
atrophy, subretinal neovascularisations and disciform scars.
Irregular autofluorescence was seen over most subretinal
neovascularisations. Autofluorescence intensity decreased in
old subretinal neovascularisations and disciform scars over
time.
CONCLUSIONS: Changes of the distribution of
autofluorescence occur in eyes with AMD over time. Fundus
autofluorescence imaging allows in vivo analysis of the
dynamics of accumulation and degradation of lipofuscin in the
RPE in eyes with AMD and documentation of metabolic activity
of the RPE.
[Autofluorescence characteristics of lipofuscin
components in different forms of late senile macular
degeneration]
Spital G; Radermacher M; Muller C; Brumm G; Lommatzsch A;
Pauleikhoff D
Augenabtlg. St. Franziskus Hospital, Munster.
Klin Monatsbl Augenheilkd (Germany) Jul 1998, 213 (1)
p23-31
BACKGROUND: Lipofuscin is the main fluorophore of the human
fundus. Because lipofuscin is the result of the accumulation
of metabolic debris in pigmentepithelial cells (RPE), the
autofluorescence can be interpreted as a clinical sign for the
metabolic activity of the RPE. In order to get informations of
RPE-function in different types of late AMD, the
autofluorescence patterns in patients with late AMD were
analyzed.
MATERIAL AND METHOD: A prospective examination of the
fundus-autofluorescence of 64 eyes of 52 patients with
different types of late AMD was performed using a confocal
scanning-laser-opthalmoscope. The autofluorescence images were
categorized in respect to the type of late AMD according to
the opthalmoscopic and fluoresceine-angiographic findings.
RESULTS: Reduced autofluorescence was found in the centre
of occult (78.6%) and classic (100%) choroidal
neovascularisations (NV) as well as in the occult NV of RPE
detachments. A loss of autofluorescence was related to the RPE
free area of RPE-tears (100%) and to RPE-atrophy (88.9%) with
sometimes increased autofluorescence at the rim. Increased
autofluorescence could be seen at the surface of
RPE-detachments (71.4%), in the area of the shrink age of RPE
in RPE-tears (100%) as well as at RPE-proliferations in small
occult NV (100%). Disciforme scars showed variable patterns of
autofluorescence.
CONCLUSION: The autofluorescence of the RPE can be analyzed
clinically with the described method. Different patterns of
autofluorescence could be revealed in different types of late
AMD. Increased autofluorescence was found in lesions with
proliferative or phagocytotic metabolic activity of the RPE
like RPE-detachments, shrinked RPE in RPE-tears or occult NV
with RPE-proliferations. The reduced autofluorescence in
occult or classical choroidal NV can be interpreted as a sign
of decompensation of the RPE and was also seen in areas with
RPE-loss.
Cigarette smoking and age-related macular
degeneration.
Chan D
Illinois College of Optometry, Chicago 60616, USA.
Optom Vis Sci (United States) Jul 1998, 75 (7)
p476-84
BACKGROUND: Age-related macular degeneration (ARMD) is one
of the leading causes of severe visual impairment among older
Americans. Several hypotheses have been proposed regarding the
pathogenesis of ARMD. The possible association of cigarette
smoking and ARMD remains controversial.
METHODS: Studies concerning the relationship between
cigarette smoking and ARMD are identified through the use of
Vision Articles Online and PubMed. Articles published since
1970 are reviewed.
RESULTS: The literature reviewed strongly supports a link
between smoking and ARMD.
CONCLUSIONS: The identification of smoking as a risk factor
can lead to early intervention. Such intervention may lessen
visual loss from this disease, which has limited medical
treatment options. (92 Refs.)
Genetic association of apolipoprotein E with
age-related macular degeneration.
Klaver CC; Kliffen M; van Duijn CM; Hofman A; Cruts M;
Grobbee DE; van Broeckhoven C; de Jong PT
Department of Epidemiology, Erasmus University Medical
School, Rotterdam, The Netherlands.
Am J Hum Genet (United States) Jul 1998, 63 (1)
p200-6
Age-related macular degeneration (AMD) is the most common
geriatric eye disorder leading to blindness and is
characterized by degeneration of the neuroepithelium in the
macular area of the eye. Apolipoprotein E (apoE), the major
apolipoprotein of the CNS and an important regulator of
cholesterol and lipid transport, appears to be associated with
neurodegeneration. The apoE gene (APOE) polymorphism is a
strong risk factor for various neurodegenerative diseases, and
the apoE protein has been demonstrated in disease-associated
lesions of these disorders. Hypothesizing that variants of
APOE act as a potential risk factor for AMD, we performed a
genetic-association study among 88 AMD cases and 901 controls
derived from the population-based Rotterdam Study in the
Netherlands. The APOE polymorphism showed a significant
association with the risk for AMD; the APOE epsilon4 allele
was associated with a decreased risk (odds ratio 0.43 [95%
confidence interval 0.21-0. 88]), and the epsilon2 allele was
associated with a slightly increased risk of AMD (odds ratio
1.5 [95% confidence interval 0.8-2. 82]). To investigate
whether apoE is directly involved in the pathogenesis of AMD,
we studied apoE immunoreactivity in 15 AMD and 10 control
maculae and found that apoE staining was consistently present
in the disease-associated deposits in AMD-maculae-that is,
drusen and basal laminar deposit. Our results suggest that
APOE is a susceptibility gene for AMD.
Age-related macular degeneration. Can we stem this
worldwide public health crisis?
Starr CE; Guyer DR; Yannuzzi LA
Massachusetts Eye and Ear Infirmary, Harvard Medical School,
Boston, USA.
Postgrad Med (United States) May 1998, 103 (5) p153-6,
161-4
Age-related macular degeneration, the leading cause of
legal blindness in people over age 60 worldwide, represents a
public health crisis that deserves the attention and
understanding of all physicians. The dry form of the disease
is more common than the wet, but the wet form causes the most
severe vision loss. Other than vision aids (e.g., glasses,
magnifiers), no treatments or preventive measures are
currently available for patients with dry macular
degeneration, and laser photocoagulation with fluorescein
angiography is the only clinically proven therapy for
neovascular disease. Indocyanine green angiography is a
promising new imaging tool that may improve detection of
patients likely to benefit from laser therapy. Until better
diagnostic and treatment options are available, early
screening and patient education offer the best hope for
reducing the widespread devastation caused by this disease.
(32 Refs.)
Moderate wine consumption is associated with
decreased odds of developing age-related macular degeneration
in NHANES-1
Obisesan TO; Hirsch R; Kosoko O; Carlson L; Parrott M
Department of Internal Medicine, Howard University Hospital,
Washington, DC 20060, USA.
J Am Geriatr Soc (United States) Jan 1998, 46 (1)
p1-7
OBJECTIVE: To determine the association between alcohol
intake and the risk of developing age-related macular
degeneration (AMD).
DESIGN: Case control study.
PARTICIPANTS: The sample consisted of 3072 adults 45 to 74
years of age with macular changes indicative of AMD who
participated in a nationally representative sample of the
first National Health Nutrition and Examination Survey
(NHANES-1) between 1971 and 1975: (a) the ophthalmology data
set and (b) the medical history questionnaire.
MAIN OUTCOME MEASURES: Alcohol intake and the risk of
developing AMD were measured. AMD was determined by staff at
the National Eye Institute by fundoscopy examination using
standardized protocol.
RESULTS: Overall, 184 individuals (6%) had AMD. We observed
a statistically significant but negative association between
AMD and the type of alcohol consumed in a bivariate model (OR
0.86; 95% CI 0.73, 0.99). In the same model, age maintained a
consistently strong association with AMD (OR 1.08; 95% CI
1.06-1.11; P < .001). Among the different types of alcohol
consumed in NHANES-1 (beer, wine, and liquor), the effect of
wine, either alone (OR 0.66; 95% CI 0.55-0.79) or in
combination with beer (OR 0.66; 95% CI 0.55-0.79) or liquor
(OR 0.74; 95% CI 0.63-0.86), dominated the negative
association observed between AMD and alcohol type.
Additionally, a statistically significant and negative
association between wine and AMD was noted after adjusting for
the effect of age, gender, income, history of congestive heart
failure, and hypertension (OR 0.81; 95% CI 0.67-0.99).
CONCLUSION: Moderate wine consumption is associated with
decreased odds of developing AMD. Health promotion and disease
prevention activities directed at cardiovascular disease may
help reduce the rate of AMD-associated blindness among older
people. The nature and pathophysiology of this association
warrant further investigation.
Treatment of macular degeneration, according to
Bangerter.
Teichmann KD
King Khaled Eye Specialist Hospital P.O. Box Riyadh 7191,
Riyadh 11 462 Kingdom of Saudi Arabia ++966 1/482 1234 ++966
1/482 1908.
Eur J Med Res (Germany) Oct 30 1997, 2 (10)
p445-54
Age-related macular degeneration (AMD) is a common cause of
visual loss among elderly patients. Although some risk factors
have been determined, the ultimate cause of the disease is not
known. For a long time, therapeutic nihilism has been the rule
among ophthalmologists confronted with such patients.
Bangerter has not shared this attitude, especially since the
time that he incidentally discovered, more than 40 years ago,
the beneficial effects of radiotherapy, in discouraging the
growth of new vessels at the posterior pole of the eye. A
variety of approaches are combined and used by Bangerter in
the treatment of the different types of AMD, including
retrobulbar injections of either vasodilating medications (in
the dry - or atrophic - type) or corticosteroids (in the wet -
or exudative - type), general medical measures aimed at
improving metabolic and vascular functions such as
supplementation with trace elements, antioxidants, and
vitamins; ozone therapy; advice to increase physical fitness,
improve nutrition, and abstain from smoking; and protection
from excessive light exposure. Being convinced of the
usefulness of his type of combination treatment, he has always
rejected undertaking controlled clinical trials, of only
single aspects of the therapy, as unethical and invalid. For
this reason, scientific journals have not proven cooperative
in several attempts at publishing his results, as collected in
retrospective surveys. Recently, however, some of the several
approaches combined by Bangerter in treating AMD have been
pronounced effective by other investigators. We present here
an overview of his treatment approaches, as few people are
aware of them, to clear up misconceptions and to set records
straight. (59 Refs.)
[Radiotherapy and age-related macular degeneration:
a review of the literature]
Schwartz LH; Schmitt T; Benchaboun M; Caputo G; Chauvaud D;
Balosso J; Faivre C; Francais C; Koenig F
Service de radiotherapie, hopital Saint-Louis, Paris,
France.
Cancer Radiother (France) 1997, 1 (3) p208-12
Macular degeneration is a major health problem. Less than
10% of the cases can be successfully treated by laser therapy.
Low dose radiation therapy (in the range of 20 Gy) appears to
decrease neovascularisation. These early results need to be
confirmed through a randomized trial. (38 Refs.)
Sun exposure and age-related macular degeneration.
An Australian case-control study.
Darzins P; Mitchell P; Heller RF
McMaster University, Division of Geriatric Medicine,
Hamilton, Ontario, Canada.
Ophthalmology (United States) May 1997, 104 (5)
p770-6
BACKGROUND: The notion that sun exposure is a risk factor
for age-related macular degeneration (AMD) is widespread, but
studies have not shown this conclusively.
METHODS: To test the hypothesis that AMD cases have greater
ocular sun exposure than control subjects, the authors
compared 409 cases with 286 control subjects resident in
Newcastle, Australia. Sensitivity to sun and glare of the
participants was characterized. Sun exposure was estimated
from detailed histories and was validated against sun-seeking
or avoidance behavior expected, given sun sensitivity and
history of treatment for skin neoplasia.
RESULTS: Contrary to the authors' hypothesis, control
subjects had greater median annual ocular sun exposure (865
hours) than cases (723 hours), Mann-Whitney U (U) = 45704, z =
-4.9, P > 0.0001. Cases had poorer tanning than did control
subjects (mean 2 = 18.2, 4 df, P = 0.001) and as young adults
were more sensitive to glare, odds ratio (OR), 2.5; 95%
confidence intervals (CIs), 1.8 to 3.5. After stratifying by
tanning ability, in the poor-tanning group, the median annual
sun exposure of control subjects (685 hours) exceeded that of
cases (619 hours), U = 6556, z = -1.9, P = 0.06. Among people
who tanned well, control subjects also had significantly
greater annual sun exposure than did cases (940 vs. 770
hours), U = 16263, z = -3.7, P = 0.0002.
CONCLUSIONS: Sensitivity to glare and poor tanning ability
are markers of increased AMD risk. Sun sensitivity confounds
study of the postulated AMD-sunlight link. Despite analyses
stratified by sun sensitivity, sun exposure was greater in
control subjects than in cases with AMD.
[Antioxidants and angiogenetic factor associated
with age-related macular degeneration (exudative type)]
Ishihara N; Yuzawa M; Tamakoshi A
Department of Ophthalmology, Nihon University School of
Medicine, Tokyo, Japan.
Nippon Ganka Gakkai Zasshi (Japan) Mar 1997, 101 (3)
p248-51
To confirm the hypothesis that antioxidants and
angiogenetic factors may be associated with the development of
age-related macular degeneration (exudative type), we compared
serum levels of vitamins A, C, and E and carotinoid, zinc,
selenium and b-FGF (basic-fibroblast growth factor) in 35
patients with age-related macular degeneration (exudative
type) with the levels in 66 controls. The average serum zinc
level was significantly lower in the patient group than in the
control group. Serum vitamin E-alpha levels also tended to be
lower. Most serum b-FGF levels were below the standard value
in each group. Based on the above results, we conclude that
subnormal levels of zinc and vitamin E may be associated with
the development of age-related macular degeneration.
Oxidative protector' enzymes in the macular retinal
pigment epithelium of aging eyes and eyes with age-related
macular degeneration
Frank R.N.
Dr. R.N. Frank, Kresge Eye Institute, Wayne State Univ. Sch.
of Medicine, Detroit, MI United States
Transactions of the American Ophthalmological Society (United
States) 1998, 96/- (635-689)
No abstract.
Alternative therapies in exudative age related
macular degeneration
Chong N.H.V.; Bird A.C.
N.H.V. Chong, Professorial Unit, Institute of Ophthalmology
(UCL), Moorfields Eye Hospital, City Road, London EC1V 2PD
United Kingdom
British Journal of Ophthalmology (United Kingdom) 1998, 82/12
(1441-1443)
No abstract.
Zinc as a treatment for age-related macular
degeneration
Olson R.J.; DeBry P.
Dr. R.J. Olson, Department of Ophthalmology, University Utah
Health Sciences Ctr., John A. Moran Eye Center, 50 North
Medical Drive, Salt Lake City, UT 84124 United States
Journal of Trace Elements in Experimental Medicine (United
States) 1998, 11/2-3 (137-145)
Evidence continues to increase that antioxidants are an
important factor in the progress and development of
age-related macular degeneration. While zinc supplementation
fits nicely in this thesis as a mineral co-factor of vital
antioxidant enzymes, the clinical evidence for oral zinc
supplementation is mixed and presently inconclusive.
Photodynamic therapy with verteporfin for choroidal
neovascularization caused by age-related macular degeneration:
Results of a single treatment in a phase 1 and 2 study
Miller J.W.; Schmidt-Erfurth U.; Sickenberg M.; Pournaras
C.J.; Laqua H.; Barbazetto I.; Zografos L.; Piguet B.; Donati
G.; Lane A.-M.; Birngruber R.; Van den Berg H.; Strong H.A.;
Manjuris U.; Gray T.; Fsadni M.; Bressler N.M.; Gragoudas
E.S.
Dr. J.W. Miller, Laser Research Laboratory, Retina Service,
Massachusetts Eye and Ear Infirmary, 243 Charles St, Boston,
MA 02114 United States
jwmiller@meei.harvard.edu
Archives of Ophthalmology (United States) 1999, 117/9
(1161-1173)
Objective: To evaluate the safety and short-term visual and
fluorescein angiographic effects of a single photodynamic
therapy treatment with verteporfin with the use of different
dosage regimens in patients with choroidal neovascularization
(CNV) from age-related macular degeneration.
Design: Nonrandomized, multicenter, open-label, clinical
trial using 5 dosage regimens.
Setting: Four ophthalmic centers in North America and
Europe providing retinal care.
Participants: Patients with subfoveal CNV caused by
age-related macular degeneration. Methods: Standardized
protocol refraction, visual acuity testing, ophthalmic
examination, color photographs, and fluorescein angiograms
were used to evaluate the effects of a single treatment of
photodynamic therapy with verteporfin. Follow-up was planned
through 3 months in 97 patients and for less than 3 months in
31 other patients.
Results: The mean visual acuity change (and range of
change) from baseline at the follow-up examination at week 12
after a single treatment with regimens 1 through 5 was -0.2
(-3 to +2), -0.9 (-9 to +5), -1.6 (-9 to +2), +0.4 (-8 to +7),
and +0.1 (-8 to +9) lines, respectively. Only the highest
light dose (150 J/cmsup 2) in regimens 2 and 3, which produced
angiographic nonperfusion of neurosensory retinal vessels,
caused marked vision loss. Some cessation of fluorescein
leakage from CNV was achieved without loss of vision when the
light dose used was less than 150 J/cmsup 2. Systemic adverse
events were rare. Cessation of fluorescein leakage from CNV
was noted in all regimens by 1 week after photodynamic
therapy. Fluorescein leakage from at least a portion of the
CNV reappeared by 4 to 12 weeks after treatment in almost all
cases. Progression of classic CNV beyond the area of CNV
identified before treatment was noted in 42 (51%) of the 83
eyes with classic CNV followed up for 3 months after a single
treatment. Eyes in which the area of any CNV leakage at 12
weeks was less than at baseline had a significantly better
visual acuity outcome (+0.8 line) than eyes in which CNV
leakage progressed (-0.8 line).
Conclusions: Photodynamic therapy with verteporfin achieved
short-term cessation of fluorescein leakage from CNV without
loss of vision or growth of classic CNV in some patients with
age- related macular degeneration. Except for nonperfusion of
neurosensory retinal vessels at a light dose of 150 J/cmsup 2,
no other adverse events were of concern. Randomized clinical
trials to investigate whether this new modality can preserve
vision in patients with CNV secondary to age-related macular
degeneration are justified.
|