[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.