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.)

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.

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.

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.)

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.

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.)

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.

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.)

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.)

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.

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.

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.

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.

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.

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.

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