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Age-related macular degeneration : a review of experimental treatments.

[Dynamics of accumulation and degradation of lipofuscin in retinal pigment epithelium in senile macular degeneration] [Autofluorescence characteristics of lipofuscin components in different forms of late senile macular degeneration] Cigarette smoking and age-related macular degeneration. enetic association of apolipoprotein ! with age-related macular degeneration. Age-related macular degeneration. Can we stem this worldwide pu"lic health crisis# $oderate wine consumption is associated with decreased odds of developing age-related macular degeneration in %&A%!'-( )reatment of macular degeneration* according to +angerter. [,adiotherapy and age-related macular degeneration: a review of the literature] 'un exposure and age-related macular degeneration. An Australian case-control study. [Antioxidants and angiogenetic factor associated with age-related macular degeneration -exudative type.] /xidative protector0 en1ymes in the macular retinal pigment epithelium of aging eyes and eyes with age-related macular degeneration. Alternative therapies in exudative age related macular degeneration. 2inc as a treatment for age-related macular degeneration. 3hotodynamic therapy with verteporfin for choroidal neovasculari1ation caused "y age-related macular degeneration: ,esults of a single treatment in a phase ( and 4 study.

Age-related macular degeneration : a review of experimental treatments. Ciulla )A5 Danis ,35 &arris A 6ndiana 7niversity $acular Degeneration Clinic and ,esearch Center* Department of

/phthalmology* 6ndiana 7niversity 'chool of $edicine* 6ndianapolis* 7'A. 'urv /phthalmol -%etherlands. 'ep-/ct (889* :; -4. p(;:-:< Age-related macular degeneration -A$D. is the leading cause of irreversi"le visual loss in the 7'A. =aser photocoagulation of choroidal neovascular mem"ranes -C%>$s. in exudative A$D is currently the only well-studied and widely accepted treatment modality. 6t is "eneficial for only a small minority of patients who show well-demarcated ?classic? C%>$s* and it destroys normal retinal tissue* creates a scotoma* and is associated with an unaccepta"ly high C%>$ persistence and recurrence rate. Conse@uently* investigators have attempted to develop new modalities for treatment of C%>$s. )hese treatment modalities can "e grouped into four maAor categories: photodynamic therapy5 pharmacologic inhi"ition of C%>$ formation with antiangiogenic agents5 surgical intervention* including excision of su"foveal C%>$s5 and radiation therapy. All of these experimental treatment modalities are directed toward destroyiing C%>$s* the end result of the exudative process* and all have limitations. )he ideal treatment of the future must "e "ased on the pathogenesis of the disease at a stage well "efore C%>$s develop. 6nvestigations in nonexudative A$D are currently focusing on several maAor areas. !pidemiologic factors* such as genetics* sunlight* and nutrition* are "eing evaluated in several large studies* including the Age-,elated !ye Disease 'tudy* with the possi"ility of ultimately limiting the risk of A$D through "ehavior modification. =aser treatment of drusen is "eing evaluated as a means of limiting the risk of C%>$ formation* although mixed results have "een reported in the small num"er of studies to date. Choroidal perfusion a"normalities have "een descri"ed in A$D* and some investigators postulate that altering "lood flow may limit the risk of C%>$ formation. %o perfusion-treatment trials have "een completed to date. -(9; ,efs..

[Dynamics of accumulation and degradation of lipofuscin in retinal pigment epithelium in senile macular degeneration] von ,uckmann A5 'chmidt B 5 Cit1ke CD5 +ird AC5 Eaco"i BD 6nstitute of /phthalmology* 7niversitats-Augenklinik* iessen. Blin $onats"l Augenheilkd - ermany. Eul (889* 4(; -(. p;4-F +ACB ,/7%D: 6t is thought that lipofuscin plays a central role in the pathogenesis of age-related macular degeneration -A$D.. )he lack of histopathological material has "een a severe limitation in our knowledge on lipofuscin in this disease. A new techni@ue has "een developed that allows in vivo imaging of fundus autofluorescence derived from lipofuscin in the retinal pigment epithelium -,3!. using a confocal =aser 'canning /phthalmoscope -='/.. De studied the dynamics of lipofuscin accumulation and degradation in patients with A$D. $A)!,6A=' A%D $!)&/D': 'erial examinations of the spatial distri"ution of fundus autofluorescence were performed in (:9 eyes of F: patients with A$D using a ='/ over

a period of (-;.G years. ,!'7=)': Cundus autofluorescence changed over time in almost all eyes studied. Areas of increased autofluorescence occurred progressively during follow up in eyes with drusen and hyperpigmentation. )he si1e of pathologic autofluorescence increased over time in almost all eyes with geographic atrophy* su"retinal neovascularisations and disciform scars. 6rregular autofluorescence was seen over most su"retinal neovascularisations. Autofluorescence intensity decreased in old su"retinal neovascularisations and disciform scars over time. C/%C=7'6/%': Changes of the distri"ution of autofluorescence occur in eyes with A$D over time. Cundus autofluorescence imaging allows in vivo analysis of the dynamics of accumulation and degradation of lipofuscin in the ,3! in eyes with A$D and documentation of meta"olic activity of the ,3!.

[Autofluorescence characteristics of lipofuscin components in different forms of late senile macular degeneration] 'pital 5 ,adermacher $5 $uller C5 +rumm 5 =ommat1sch A5 3auleikhoff D Augena"tlg. 't. Cran1iskus &ospital* $unster. Blin $onats"l Augenheilkd - ermany. Eul (889* 4(; -(. p4;-;( +ACB ,/7%D: =ipofuscin is the main fluorophore of the human fundus. +ecause lipofuscin is the result of the accumulation of meta"olic de"ris in pigmentepithelial cells -,3!.* the autofluorescence can "e interpreted as a clinical sign for the meta"olic activity of the ,3!. 6n order to get informations of ,3!-function in different types of late A$D* the autofluorescence patterns in patients with late A$D were analy1ed. $A)!,6A= A%D $!)&/D: A prospective examination of the fundus-autofluorescence of <: eyes of G4 patients with different types of late A$D was performed using a confocal scanning-laser-opthalmoscope. )he autofluorescence images were categori1ed in respect to the type of late A$D according to the opthalmoscopic and fluoresceineangiographic findings. ,!'7=)': ,educed autofluorescence was found in the centre of occult -F9.<H. and classic -(IIH. choroidal neovascularisations -%>. as well as in the occult %> of ,3! detachments. A loss of autofluorescence was related to the ,3! free area of ,3!-tears -(IIH. and to ,3!-atrophy -99.8H. with sometimes increased autofluorescence at the rim. 6ncreased autofluorescence could "e seen at the surface of ,3!-detachments -F(.:H.* in the area of the shrink age of ,3! in ,3!-tears -(IIH. as well as at ,3!proliferations in small occult %> -(IIH.. Disciforme scars showed varia"le patterns of autofluorescence.

C/%C=7'6/%: )he autofluorescence of the ,3! can "e analy1ed clinically with the descri"ed method. Different patterns of autofluorescence could "e revealed in different types of late A$D. 6ncreased autofluorescence was found in lesions with proliferative or phagocytotic meta"olic activity of the ,3! like ,3!-detachments* shrinked ,3! in ,3!tears or occult %> with ,3!-proliferations. )he reduced autofluorescence in occult or classical choroidal %> can "e interpreted as a sign of decompensation of the ,3! and was also seen in areas with ,3!-loss.

Cigarette smoking and age-related macular degeneration. Chan D 6llinois College of /ptometry* Chicago <I<(<* 7'A. /ptom >is 'ci -7nited 'tates. Eul (889* FG -F. p:F<-9: +ACB ,/7%D: Age-related macular degeneration -A,$D. is one of the leading causes of severe visual impairment among older Americans. 'everal hypotheses have "een proposed regarding the pathogenesis of A,$D. )he possi"le association of cigarette smoking and A,$D remains controversial. $!)&/D': 'tudies concerning the relationship "etween cigarette smoking and A,$D are identified through the use of >ision Articles /nline and 3u"$ed. Articles pu"lished since (8FI are reviewed. ,!'7=)': )he literature reviewed strongly supports a link "etween smoking and A,$D. C/%C=7'6/%': )he identification of smoking as a risk factor can lead to early intervention. 'uch intervention may lessen visual loss from this disease* which has limited medical treatment options. -84 ,efs..

enetic association of apolipoprotein ! with age-related macular degeneration. Blaver CC5 Bliffen $5 van DuiAn C$5 &ofman A5 Cruts $5 ro""ee D!5 van +roeckhoven C5 de Eong 3) Department of !pidemiology* !rasmus 7niversity $edical 'chool* ,otterdam* )he %etherlands. Am E &um enet -7nited 'tates. Eul (889* <; -(. p4II-< Age-related macular degeneration -A$D. is the most common geriatric eye disorder leading to "lindness and is characteri1ed "y degeneration of the neuroepithelium in the macular area of the eye. Apolipoprotein ! -apo!.* the maAor apolipoprotein of the C%'

and an important regulator of cholesterol and lipid transport* appears to "e associated with neurodegeneration. )he apo! gene -A3/!. polymorphism is a strong risk factor for various neurodegenerative diseases* and the apo! protein has "een demonstrated in disease-associated lesions of these disorders. &ypothesi1ing that variants of A3/! act as a potential risk factor for A$D* we performed a genetic-association study among 99 A$D cases and 8I( controls derived from the population-"ased ,otterdam 'tudy in the %etherlands. )he A3/! polymorphism showed a significant association with the risk for A$D5 the A3/! epsilon: allele was associated with a decreased risk -odds ratio I.:; [8GH confidence interval I.4(-I. 99].* and the epsilon4 allele was associated with a slightly increased risk of A$D -odds ratio (.G [8GH confidence interval I.9-4. 94].. )o investigate whether apo! is directly involved in the pathogenesis of A$D* we studied apo! immunoreactivity in (G A$D and (I control maculae and found that apo! staining was consistently present in the disease-associated deposits in A$D-maculae-that is* drusen and "asal laminar deposit. /ur results suggest that A3/! is a suscepti"ility gene for A$D.

Age-related macular degeneration. Can we stem this worldwide pu"lic health crisis# 'tarr C!5 uyer D,5 Jannu11i =A $assachusetts !ye and !ar 6nfirmary* &arvard $edical 'chool* +oston* 7'A. 3ostgrad $ed -7nited 'tates. $ay (889* (I; -G. p(G;-<* (<(-: Age-related macular degeneration* the leading cause of legal "lindness in people over age <I worldwide* represents a pu"lic health crisis that deserves the attention and understanding of all physicians. )he dry form of the disease is more common than the wet* "ut the wet form causes the most severe vision loss. /ther than vision aids -e.g.* glasses* magnifiers.* no treatments or preventive measures are currently availa"le for patients with dry macular degeneration* and laser photocoagulation with fluorescein angiography is the only clinically proven therapy for neovascular disease. 6ndocyanine green angiography is a promising new imaging tool that may improve detection of patients likely to "enefit from laser therapy. 7ntil "etter diagnostic and treatment options are availa"le* early screening and patient education offer the "est hope for reducing the widespread devastation caused "y this disease. -;4 ,efs..

$oderate wine consumption is associated with decreased odds of developing agerelated macular degeneration in %&A%!'-( /"isesan )/5 &irsch ,5 Bosoko /5 Carlson =5 3arrott $ Department of 6nternal $edicine* &oward 7niversity &ospital* Dashington* DC 4II<I* 7'A.

E Am eriatr 'oc -7nited 'tates. Ean (889* :< -(. p(-F /+E!C)6>!: )o determine the association "etween alcohol intake and the risk of developing age-related macular degeneration -A$D.. D!'6 %: Case control study. 3A,)6C63A%)': )he sample consisted of ;IF4 adults :G to F: years of age with macular changes indicative of A$D who participated in a nationally representative sample of the first %ational &ealth %utrition and !xamination 'urvey -%&A%!'-(. "etween (8F( and (8FG: -a. the ophthalmology data set and -". the medical history @uestionnaire. $A6% /7)C/$! $!A'7,!': Alcohol intake and the risk of developing A$D were measured. A$D was determined "y staff at the %ational !ye 6nstitute "y fundoscopy examination using standardi1ed protocol. ,!'7=)': /verall* (9: individuals -<H. had A$D. De o"served a statistically significant "ut negative association "etween A$D and the type of alcohol consumed in a "ivariate model -/, I.9<5 8GH C6 I.F;* I.88.. 6n the same model* age maintained a consistently strong association with A$D -/, (.I95 8GH C6 (.I<-(.((5 3 K .II(.. Among the different types of alcohol consumed in %&A%!'-( -"eer* wine* and li@uor.* the effect of wine* either alone -/, I.<<5 8GH C6 I.GG-I.F8. or in com"ination with "eer -/, I.<<5 8GH C6 I.GG-I.F8. or li@uor -/, I.F:5 8GH C6 I.<;-I.9<.* dominated the negative association o"served "etween A$D and alcohol type. Additionally* a statistically significant and negative association "etween wine and A$D was noted after adAusting for the effect of age* gender* income* history of congestive heart failure* and hypertension -/, I.9(5 8GH C6 I.<F-I.88.. C/%C=7'6/%: $oderate wine consumption is associated with decreased odds of developing A$D. &ealth promotion and disease prevention activities directed at cardiovascular disease may help reduce the rate of A$D-associated "lindness among older people. )he nature and pathophysiology of this association warrant further investigation.

)reatment of macular degeneration* according to +angerter. )eichmann BD Bing Bhaled !ye 'pecialist &ospital 3./. +ox ,iyadh F(8(* ,iyadh (( :<4 Bingdom of 'audi Ara"ia LL8<< (M:94 (4;: LL8<< (M:94 (8I9. !ur E $ed ,es - ermany. /ct ;I (88F* 4 -(I. p::G-G: Age-related macular degeneration -A$D. is a common cause of visual loss among elderly

patients. Although some risk factors have "een determined* the ultimate cause of the disease is not known. Cor a long time* therapeutic nihilism has "een the rule among ophthalmologists confronted with such patients. +angerter has not shared this attitude* especially since the time that he incidentally discovered* more than :I years ago* the "eneficial effects of radiotherapy* in discouraging the growth of new vessels at the posterior pole of the eye. A variety of approaches are com"ined and used "y +angerter in the treatment of the different types of A$D* including retro"ul"ar inAections of either vasodilating medications -in the dry - or atrophic - type. or corticosteroids -in the wet - or exudative - type.* general medical measures aimed at improving meta"olic and vascular functions such as supplementation with trace elements* antioxidants* and vitamins5 o1one therapy5 advice to increase physical fitness* improve nutrition* and a"stain from smoking5 and protection from excessive light exposure. +eing convinced of the usefulness of his type of com"ination treatment* he has always reAected undertaking controlled clinical trials* of only single aspects of the therapy* as unethical and invalid. Cor this reason* scientific Aournals have not proven cooperative in several attempts at pu"lishing his results* as collected in retrospective surveys. ,ecently* however* some of the several approaches com"ined "y +angerter in treating A$D have "een pronounced effective "y other investigators. De present here an overview of his treatment approaches* as few people are aware of them* to clear up misconceptions and to set records straight. -G8 ,efs..

[,adiotherapy and age-related macular degeneration: a review of the literature] 'chwart1 =&5 'chmitt )5 +encha"oun $5 Caputo 5 Chauvaud D5 +alosso E5 Caivre C5 Crancais C5 Boenig C 'ervice de radiotherapie* hopital 'aint-=ouis* 3aris* Crance. Cancer ,adiother -Crance. (88F* ( -;. p4I9-(4 $acular degeneration is a maAor health pro"lem. =ess than (IH of the cases can "e successfully treated "y laser therapy. =ow dose radiation therapy -in the range of 4I y. appears to decrease neovascularisation. )hese early results need to "e confirmed through a randomi1ed trial. -;9 ,efs..

'un exposure and age-related macular degeneration. An Australian case-control study. Dar1ins 35 $itchell 35 &eller ,C $c$aster 7niversity* Division of eriatric $edicine* &amilton* /ntario* Canada. /phthalmology -7nited 'tates. $ay (88F* (I: -G. pFFI-< +ACB ,/7%D: )he notion that sun exposure is a risk factor for age-related macular

degeneration -A$D. is widespread* "ut studies have not shown this conclusively. $!)&/D': )o test the hypothesis that A$D cases have greater ocular sun exposure than control su"Aects* the authors compared :I8 cases with 49< control su"Aects resident in %ewcastle* Australia. 'ensitivity to sun and glare of the participants was characteri1ed. 'un exposure was estimated from detailed histories and was validated against sun-seeking or avoidance "ehavior expected* given sun sensitivity and history of treatment for skin neoplasia. ,!'7=)': Contrary to the authors0 hypothesis* control su"Aects had greater median annual ocular sun exposure -9<G hours. than cases -F4; hours.* $ann-Dhitney 7 -7. N :GFI:* 1 N -:.8* 3 O I.III(. Cases had poorer tanning than did control su"Aects -mean 4 N (9.4* : df* 3 N I.II(. and as young adults were more sensitive to glare* odds ratio -/,.* 4.G5 8GH confidence intervals -C6s.* (.9 to ;.G. After stratifying "y tanning a"ility* in the poor-tanning group* the median annual sun exposure of control su"Aects -<9G hours. exceeded that of cases -<(8 hours.* 7 N <GG<* 1 N -(.8* 3 N I.I<. Among people who tanned well* control su"Aects also had significantly greater annual sun exposure than did cases -8:I vs. FFI hours.* 7 N (<4<;* 1 N -;.F* 3 N I.III4. C/%C=7'6/%': 'ensitivity to glare and poor tanning a"ility are markers of increased A$D risk. 'un sensitivity confounds study of the postulated A$D-sunlight link. Despite analyses stratified "y sun sensitivity* sun exposure was greater in control su"Aects than in cases with A$D.

[Antioxidants and angiogenetic factor associated with age-related macular degeneration -exudative type.] 6shihara %5 Ju1awa $5 )amakoshi A Department of /phthalmology* %ihon 7niversity 'chool of $edicine* )okyo* Eapan. %ippon anka akkai 2asshi -Eapan. $ar (88F* (I( -;. p4:9-G( )o confirm the hypothesis that antioxidants and angiogenetic factors may "e associated with the development of age-related macular degeneration -exudative type.* we compared serum levels of vitamins A* C* and ! and carotinoid* 1inc* selenium and "-C C -"asicfi"ro"last growth factor. in ;G patients with age-related macular degeneration -exudative type. with the levels in << controls. )he average serum 1inc level was significantly lower in the patient group than in the control group. 'erum vitamin !-alpha levels also tended to "e lower. $ost serum "-C C levels were "elow the standard value in each group. +ased on the a"ove results* we conclude that su"normal levels of 1inc and vitamin ! may "e associated with the development of age-related macular degeneration.

/xidative protector0 en1ymes in the macular retinal pigment epithelium of aging eyes and eyes with age-related macular degeneration Crank ,.%. Dr. ,.%. Crank* Bresge !ye 6nstitute* Dayne 'tate 7niv. 'ch. of $edicine* Detroit* $6 7nited 'tates )ransactions of the American /phthalmological 'ociety -7nited 'tates. (889* 8<M- -<;G<98. %o a"stract.

Alternative therapies in exudative age related macular degeneration Chong %.&.>.5 +ird A.C. %.&.>. Chong* 3rofessorial 7nit* 6nstitute of /phthalmology -7C=.* $oorfields !ye &ospital* City ,oad* =ondon !C(> 43D 7nited Bingdom +ritish Eournal of /phthalmology -7nited Bingdom. (889* 94M(4 -(::(-(::;. %o a"stract.

2inc as a treatment for age-related macular degeneration /lson ,.E.5 De+ry 3. Dr. ,.E. /lson* Department of /phthalmology* 7niversity 7tah &ealth 'ciences Ctr.* Eohn A. $oran !ye Center* GI %orth $edical Drive* 'alt =ake City* 7) 9:(4: 7nited 'tates Eournal of )race !lements in !xperimental $edicine -7nited 'tates. (889* ((M4-; -(;F(:G. !vidence continues to increase that antioxidants are an important factor in the progress and development of age-related macular degeneration. Dhile 1inc supplementation fits nicely in this thesis as a mineral co-factor of vital antioxidant en1ymes* the clinical evidence for oral 1inc supplementation is mixed and presently inconclusive.

3hotodynamic therapy with verteporfin for choroidal neovasculari1ation caused "y age-related macular degeneration: ,esults of a single treatment in a phase ( and 4 study $iller E.D.5 'chmidt-!rfurth 7.5 'icken"erg $.5 3ournaras C.E.5 =a@ua &.5 +ar"a1etto 6.5 2ografos =.5 3iguet +.5 Donati .5 =ane A.-$.5 +irngru"er ,.5 >an den +erg &.5 'trong

&.A.5 $anAuris 7.5 ray ).5 Csadni $.5 +ressler %.$.5 ragoudas !.'. Dr. E.D. $iller* =aser ,esearch =a"oratory* ,etina 'ervice* $assachusetts !ye and !ar 6nfirmary* 4:; Charles 't* +oston* $A I4((: 7nited 'tates AwmillerPmeei.harvard.edu Archives of /phthalmology -7nited 'tates. (888* ((FM8 -((<(-((F;. /"Aective: )o 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 neovasculari1ation -C%>. from agerelated macular degeneration. Design: %onrandomi1ed* multicenter* open-la"el* clinical trial using G dosage regimens. 'etting: Cour ophthalmic centers in %orth America and !urope providing retinal care. 3articipants: 3atients with su"foveal C%> caused "y age-related macular degeneration. $ethods: 'tandardi1ed 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. Collow-up was planned through ; months in 8F patients and for less than ; months in ;( other patients. ,esults: )he mean visual acuity change -and range of change. from "aseline at the followup examination at week (4 after a single treatment with regimens ( through G was -I.4 --; to L4.* -I.8 --8 to LG.* -(.< --8 to L4.* LI.: --9 to LF.* and LI.( --9 to L8. lines* respectively. /nly the highest light dose -(GI EMcmsup 4. in regimens 4 and ;* which produced angiographic nonperfusion of neurosensory retinal vessels* caused marked vision loss. 'ome cessation of fluorescein leakage from C%> was achieved without loss of vision when the light dose used was less than (GI EMcmsup 4. 'ystemic adverse events were rare. Cessation of fluorescein leakage from C%> was noted in all regimens "y ( week after photodynamic therapy. Cluorescein leakage from at least a portion of the C%> reappeared "y : to (4 weeks after treatment in almost all cases. 3rogression of classic C%> "eyond the area of C%> identified "efore treatment was noted in :4 -G(H. of the 9; eyes with classic C%> followed up for ; months after a single treatment. !yes in which the area of any C%> leakage at (4 weeks was less than at "aseline had a significantly "etter visual acuity outcome -LI.9 line. than eyes in which C%> leakage progressed --I.9 line.. Conclusions: 3hotodynamic therapy with verteporfin achieved short-term cessation of fluorescein leakage from C%> without loss of vision or growth of classic C%> in some patients with age- related macular degeneration. !xcept for nonperfusion of neurosensory retinal vessels at a light dose of (GI EMcmsup 4* no other adverse events were of concern. ,andomi1ed clinical trials to investigate whether this new modality can preserve vision in patients with C%> secondary to age-related macular degeneration are Austified. [Antioxidants for prophylaxis of eye diseases]

Balu1ny E Bliniki /kulistyc1neA A$ w +ydgos1c1y. Blin /c1na -3oland. Ce" (88<* 89 -4. p(:(-; )he contemporary literature has widely descri"ed 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. )his paper presents pu"lications which stress the importance of antioxidants use in prophylaxis of cataract and age-related macular degeneration. 3ositive antioxidants role was proved "oth in experimental research and in clinical o"servations. -48 ,efs..

A prospective study of cigarette smoking and age-related macular degeneration in women 'eddon E$* Dillett DC* 'pei1er C!* &ankinson '! !pidemiology 7nit* $assachusetts !ye and !ar 6nfirmary* +oston* $A I4((:* 7'A. Eournal of the American $edical Association -7'A.* (88<* 4F<M(: -((:(-((:<. /"Aective. - )o evaluate the relationship "etween cigarette smoking and incidence of agerelated macular degeneration -A$D. among women. Design. - 3rospective cohort study with (4 years of follow-up -(89I to (884.* in which information on smoking ha"its was updated every 4 years. 'etting. - !leven states throughout the 7nited 'tates. 3articipants. - A total of ;( 9:; registered nurses enrolled in the %urses0 &ealth 'tudy who were aged GI to G8 years in (89I and did not report a diagnosis of cancer or A$D at the "eginning of the study. Additional women entered the analytic cohort as they reached GI years of age. $ain /utcome $easure. - 6ncidence of A$D with visual loss. ,esults. - During GG< ;;9 person-years of follow-up* 4(G women were newly diagnosed as having A$D. After adAusting for other risk factors for A$D* women who currently smoked 4G or more cigarettes per day had a relative risk -,,. of A$D of 4.: -8GH confidence interval -C6.* (.:-:.I. compared with women who never smoked. 3ast smokers of this amount also had a 4-fold increased risk -,,N4.I5 8GH C6* (.4-;.:. relative to never smokers. Compared with current smokers* little reduction in risk was suggested even after @uitting smoking for (G or more years. ,isk of A$D also increased with an increasing num"er of pack-years smoked -3 for trend K.II(.5 among women who smoked for <G or more peck-years* the risk was 4.: times the risk of never smokers -8GH C6* (.G-;.9.. Analyses of dry and exudative types of A$D and other alternative definitions of A$D revealed similar results.

Conclusions. - Cigarette smoking is an independent and avoida"le risk factor for A$D among women. +ecause A$D is the most common cause of severe visual impairment among the elderly and treatment is not availa"le or is ineffective for most patients* reducing the risk of this disease is another important reason to avoid smoking.

$ulticenter ophthalmic and nutritional age-related macular degeneration studypart (: design* su"5ects and procedures. ,icher ' !ye Clinic ((4e* D>A $edical Center* %orth Chicago* 6= <II<:* 7'A. E Am /ptom Assoc -7nited 'tates. Ean (88<* <F -(. p(4-48 +ACB ,/7%D: A prospective (9 month* dou"le-"lind case-controlled study was designed to determine whether a specific over-the-counter multivitaminMmineralMantioxidant nutrient capsule taken twice daily prevents the progression of* or improves the outcome of non-exudative A,$D. )wo randomly assigned experimental A,$D groups are compared to each other* to age matched A,$D-free case controls and to (88: %&A%!' 666 nutritional data. $!)&/D': )hirty-two dry A,$D patients assigned to group one -place"o. and ;8 dry A,$D patients were assigned to group two -/cuguard* a "road spectrum antioxidant capsule.. A third age and sex matched A,$D-free case control group of (; patients who met the same entrance criteria were also selected. All participants underwent thorough visual and nutritional evaluation prior to initiation of the study. +oth ophthalmic tests and dietetic assessments were also performed at <* (4 and (9 months following a 4-week initiation period. ,!'7=)': 6n comparison to %&A%!'-666 age stratified population data and the ,ecommended Daily Allowance -"ut not case controls.* the A,$D population manifested decreased intake of nutrients vital to cardiovascular health: vitamin !* magnesium* 1inc* vitamin +< and folic acid. )he two randomly assigned experimental groups were well matched* with little difference in "aseline demographic* ocular* hematologic and pre-intervention symptoms. )here were differences in nutritional intake "etween the two groups* due primarily to significantly higher percent ideal "ody weight in group two.

$ulticenter ophthalmic and nutritional age-related macular degeneration study-part 4: antioxidant intervention and conclusions. ,icher ' !ye Clinic ((4e* D>A $edical Center* %orth Chicago* 6= <II<:* 7'A. E Am /ptom Assoc -7nited 'tates. Ean (88<* <F -(. p;I-:8

+ACB ,/7%D: )he experimental design* su"Aects* procedures and "aseline data for the prospective dou"le "lind dry A,$D-antioxidant intervention study have "een descri"ed in 3art (. $!)&/D': At eight D>A medical centers* ;4 patients -group one. were assigned a place"o and ;8 patients -group two. a ?"road spectrum? antioxidant capsule. Data was collected in five areas: demographic5 ophthalmic5 dietary analysis of daily food intake5 serum analysis5 and adverse gastrointestinal symptoms. Data was serially ac@uired at "aseline* < months* (4 months and (9 months* and was analy1ed "y univariate repeated factors A%/>A* p N I.IG. ,!'7=)': roup two -antioxidant po +6D. maintained their distance =og$A, visual acuity -p N I.I;.* while there was a trend toward "oth sta"ili1ed near $ print -p N I.IF. and < cycleMdegree contrast sensitivity -p approximately I.(I.* in left eyes. &owever* group two -antioxidant. also had increased cortical opacification of the right lens -p N I.I:.* compared to group one -place"o.. 'elf perceived sta"ili1ation of vision was reported "y su"Aects in group two and supported the o"Aective data -3earson chi s@uare5 p N I.IG.. C/%C=7'6/%':A specific (: component antioxidant capsule taken twice daily sta"ili1ed "ut did not improve dry A,$D over the study period of (.G years. )he A,$D sta"ili1ed eyes had less advanced disease functionally "ut not "y fundus appearance. Decreased intake of cardioprotective nutrients -vitamin !* 1inc* magnesium* +< and folate. in A,$D patients remained constant over the course of the trial.

,adial distri"ution of tocopherols in rhesus monkey retina and retinal pigment epithelium-choroid. Cra"tree D>* Adler AE* 'nodderly D$ 'chepens !ye ,esearch 6nstitute* &arvard $edical 'chool* +oston* $A I4((:* 7'A. 6nvest /phthalmol >is 'ci -7nited 'tates. Ean (88<* ;F -(. p<(-F< 37,3/'!. )o map vitamin ! as a function of distance from the foveal center in the primate retina and retinal pigment epithelium -,3!.-choroid. $!)&/D'. !yecups 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. )wo different types of dissection were performed. Cor one type* the authors used circular trephines with diameters of (* :* 9* and (I mm -(*:-D.* whereas for the other type the diameters were 4* G* 9* and sometimes (I mm -4*G-D.. Dhen possi"le* the neural retina was separated from the ,3!-choroid. )issues were analy1ed for vitamin !* retinyl palmitate* and protein.

,!'7=)'. 'urface area* volume* and protein were used as indexes of the amount of tissue analy1ed. Distri"utions of vitamin ! in neural retina were dependent on the tissue metric used and type of dissection performed. &owever* regardless of the tissue metric used* the central (-mm disc of the (*:-D was* on average* higher in vitamin ! content than was the central 4-mm disc of the 4*G-D. )his was particularly true when volume was the tissue metric. Crom the average values of vitamin ! in a series of concentric discs* a composite plot of the vitamin ! concentration in the neural retina was generated that took into consideration "oth types of dissection. )hat plot displayed a local maximum in the fovea and then precipitously declined to a minimum in the region "etween I.G and (.I mm eccentricity -near the foveal crest.5 at greater eccentricities* the vitamin ! concentration rose to a value similar to that in the fovea* i.e.* the composite plot indicated that vitamin ! has a >-shaped distri"ution in the central neural retina. >itamin ! distri"ution in the ,3!-choroid* with surface area as the tissue metric* also was measured. Cor this tissue* the foveal region displayed a local maximum. C/%C=7'6/%'. +y com"ining the results of two different types of dissection* the authors found that in the neural retina* vitamin ! displayed a minimum near the foveal crest. )his minimum correlated MManatomically with the site at which areolar -geographic. atrophy fre@uently occurs in retinal pigment epithelial cells in the human disease* agerelated macular degeneration.

)reatment of senile macular degeneration with inkgo "ilo"a extract. A preliminary dou"le-"lind* drug versus place"o study =e"uisson D.A.5 =eroy =.5 ,igal . Centre $edico-Chirurgical Coch* C 84(G( 'uresnes Cedex Crance 3resse $ed. -Crance.* (89<* (GM;( -(GG<-(GG9. 'enile macular degeneration is a fre@uent cause of "lindness for which there is no satisfactory medical treatment. A dou"le-"lind trial comparing inkgo "ilo"a extract with place"o was conducted in (I out-patients at the &opital Coch. Drug effectiveness was assessed on the results of fundoscopy and of measurements of visual acuity and visual field. 6n spite of the small population sample* a statistically significant improvement in long distance visual acuity was o"served after treatment with inkgo "ilo"a extract. )he assumed pathogenesis of senile macular degeneration is discussed with emphasis on free oxygenated radicals.

&ydergine - a new promise in neuro-retinal disorders 'hukla $. A.$.7. 6nstitute of /phthalmology* Aligarh* 7.3. 6ndia Afro-Asian E. /phthalmol. -6ndia.* (898* 9M( -49-;I.

&ydergine -co-dergocrine mesylate. was clinically evaluated in (<( eyes of 8< 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. Dhile all the patients received this treatment with ta"lets* ;4 patients* in addition* received this therapy in inAecta"le form also. +eneficial results in terms of improvement in visual acuity were noticed in G4 -;4.;IH. eyes after three months of treatment. =ong-term visual improvement or sta"ilisation of visual acuity was seen in :I eyes at < months and 48 eyes "etween six months-one year respectively. )he "est visual results were o"tained in pathological myopia* anterior ischaemic optic neuropathy* primary optic atrophy and typical retinitis pigmentosa. Dhile the initial results of &ydergine treatment are @uite encouraging in the treatment of certain neuroretinal disorders primarily with a neuronal transmission defect andMor vascular ischaemic pathology* the cost factor is a positive draw"ack particularly cases re@uiring long-term treatment.

6nhi"ition of glutathione reductase "y flavonoids. A structure-activity study !lliott A.E.5 'chei"er '.A.5 )homas C.5 3ardini ,.'. Department of +iochemistry* 7niversity of %evada* Allie $. =ee =a". of Cancer ,esearch* $ail 'top ;;I* ,eno* %> 98GGF 7'A +iochem 3harmacol. (884 /ct 4I5::-9.:(<I;-9. A structure-activity study of fourteen chemically related flavonoids was conducted to evaluate their a"ilities to inhi"it glutathione reductase - ,.. +y comparing the 6GI values of flavonoids from different classes possessing an identical hydroxyl configuration* we determined the following order of potency for inhi"ition of ,: anthocyanidin O dihydroflavonol N chalcone O flavonol O catechin. !n1yme inhi"ition "y delphinidin chloride and myricetin was partially prevented in a %4 atmosphere which implicates a role for oxygen in the mechanism of inhi"ition. )o determine the role of oxygen species in en1yme inhi"ition* , was preincu"ated with either mannitol* diethylenetriaminepenta-acetic acid -D!)A3AC.* superoxide dismutase -'/D.* catalase -CA).* or '/D and CA) prior to assays for en1yme inhi"ition "y flavonoids. !n1yme inhi"ition "y delphinidin chloride and myricetin was suppressed "y the addition of '/D* suggesting that superoxide -/4.-. is involved. &owever* inhi"ition "y @uercetin and morin was not sensitive to antioxidants. )o further investigate the role of /4.- in , inhi"ition* a superoxide generating system was utili1ed in the presence and a"sence of flavonoid. )he /4.- generating system failed to inhi"it , in the a"sence of flavonoid "ut enhanced the inhi"ition "y myricetin* indicating that the /4.- did not directly inhi"it , "ut reacted directly with certain flavonoids to form a reactive intermediate which* in turn* inhi"ited ,. )hese findings suggest that the mechanism of inhi"ition of , "y flavonoids is complex and may have oxygen-dependent and oxygen-independent components.

7lavonoids* a class of natural products of high pharmacological potency &avsteen +. +iochem 3harmacol (89; Apr (5;4-F.:((:(-9 A review has "een presented of the "iochemistry and pharmacology of a class of natural products* the flavonoids. )hese su"stances which are widely distri"uted in the plant kingdom and present in considera"le @uantities in common food products* spices and "everages have in a concentrated form -3ropolis. "een used since ancient times "y physicians and laymen to treat a great variety of human diseases "ut they have yet to pass the tests of modern* controlled* clinical experimentation. An attempt has "een made to present the fundamental evidence from the "asic "iological sciences which is re@uired to stimulate the interest of the clinicians in this new field. )he few existing reports on the careful pharmacodynamic* pharmacokinetic and clinical studies which have "een made have "een summari1ed to provide a "asis for a full-scale investigation of the therapeutic potential of flavonoids.

,esults with anthocyanosides from 8accinium myrtillus e9uivalent to 4:; of anthocyanidines in the treatment of haemorrhagic diathesis due to defective primary haemostasis 3iovella C.5 Almasio 3.5 ,icetti $.$.5 et al. 6st. Clin. $ed. 6 Adolfo Cerrata* 7niv. 3avia 6taly a11. $ed. 6tal. -6taly.* (89(* (:IM(I -::G-::8. %o a"stract.

'tudies on vaccinium myrtillus anthocyanosides. 6. 8asoprotective and antiinflammatory activity =ietti A.5 Cristoni A.5 3icci $. ,es. =a". 6nverni della +effa* $ilan 6taly Ar1neimittelforschung (8F<54<-G.:948-;4 A >accinium myrtillus anthocyanoside preparation -e@uivalent to 4GH anthocyanidin. demonstrated significant vasoprotective and antioedema properties in experimental animals. 6n ra""its* the skin capillary permea"ility increase* due to chloroform* was reduced "oth after i.p. -4G-(II mgMkg. and oral administration -4II-:II mgMkg. of anthocyanosides. )heir activity was more lasting in comparison to rutin or mepyramine and this did not seem to "e due to a specific antagonism towards inflammatory process

mediators such as histamine or "radykinin. !xperiments carried out in rats demonstrated that >accinium myrtillus anthocyanosides were effective "oth in skin permea"ility test and on vascular resistance of rats fed a 3 factor deficient diet. 6n the former test effective doses were in the range of 4G-(II mgMkg -"y oral route.. 6n "oth animal species investigated* anthocyanosides were twice as active as the flavonoid rutin. >accinium myrtillus anthocyanosides "y oral route inhi"ited 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. ,ate of spread of geographic atrophy and visual loss 'chat1 &.5 $cDonald &.,. ,etina ,esearch Cund of 't. $ary0s &ospital and $edical Center* 'an Crancisco* CA 7'A /phthalmology. (898 /ct58<-(I.:(G:(-G(. )he authors studied GI eyes with atrophic -dry. macular degeneration -geographic atrophy of age-related macular degeneration - A$D.* in GI consecutive patients for 4 to < years -average* ;.: years.. )here were ;G women and (G men ranging in age from <I to 98 years -average* F; years.. )he areas of atrophy tended to follow the disappearance or flattening of soft drusen* pigment epithelial detachment* or reticular mottling of the retinal pigment epithelium. )he atrophic areas were multifocal in 4I of the GI eyes. Atrophy of the retinal pigment epithelium was followed "y atrophy of the choriocapillaris. )he atrophic areas tended to expand -average rate in one direction* (;8 microm per year. and cause gradual loss of central visual acuity. )he rate of significant visual loss -from 4IMGI or "etter to 4IM(II or worse. was 9H of eyes per year. )here was a tendency toward resistance of the spread of atrophy into the fovea. )he atrophy tended to expand faster in patients under age FG and slower in patients aged FG and over. 'u"retinal neovasculari1ation developed in ten of the GI eyes.

'tudy of aging macular degeneration in China Du =& 2hongshan /phthalmic Center* 'un Jat-sen 7niversity of $edical 'ciences* uang1hou* China. Epn E /phthalmol (89F5;(-;.:;:8-<F 'tudies of the epidemiology* pathogenetic factors and visual function of aging macular degeneration -A$D. show that it has "ecome an ocular disease worth noticing in China. Although most A$D 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 meta"olism may "e helpful for early prevention and treatment of A$D. 6t will also "e an important factor in the prevention of "lindness in Asian nations.

'u"retinal neovasculari1ation in senile macular degeneration +erkow E.D. Department of /phthalmology* reater +altimore $edical Center* +altimore* $D Am E /phthalmol (89: Ce"58F-4.:(:;-F Dhen fluorescein angiograms from G<; patients with senile macular degeneration examined at a large community hospital during a 8.G-year period were retrospectively reviewed* 4II patients were found to have a dry atrophic type of senile macular degeneration* consisting of drusen and retinal pigment epithelial changes. /f the ;<; patients with exudative senile macular degeneration* 4:: had su"retinal neovascular mem"ranes. 'eventy-eight mem"ranes were less than ( disk diameter in si1e. $ost of the large -(GF of 44:. and small -:: of F9. mem"ranes showed a predilection for the fovea. /nly (; large and six small neovascular mem"ranes were 4II mum or more from the center of the foveal avascular 1one.

Delayed macular choriocapillary circulation in age related macular 2hao E.5 Cram"ach D.A.5 =ee 3.3.5 =ee $.5 =ope1 3.C. Doheny !ye 6nstitute* Department of /phthalmology* 7niv. 'outhern California 'ch. $ed.* (:GI 'an 3a"lo 'treet* =os Angeles* CA 8II;; 7'A 6nt /phthalmol (88G5(8-(.:(-(4 3urpose. )o investigate the macular choriocapillary circulation -$CC. in eyes with agerelated macular degeneration -A,$D. and to correlate these findings with the associated clinical and angiographic drusen characteristics. $ethods. 'canning laser ophthalmoscope fluorescein videoangiography was performed on ;: eyes with age-related macular degeneration and eight age-matched normal volunteers. Drusen characteristics were assessed using the Disconsin age-related maculopathy grading scale. ,esults. A delayed macular choriocapillary circulation -D$CC. was defined as a macular choriocapillary filling time greater than ; standard deviations from the normal mean -greater than G seconds.. %ine -4<H. of the ;: eyes with A,$D were found to have a D$CC. After age adAustment* eyes with D$CC were more likely to have geographic atrophy of the retinal pigment epithelium -p N I.II;. or choroidal neovasculari1ation p N I.IF. than were eyes with a normal $CC. ,egional differences in choriocapillary filling

times were present in the eyes with a D$CC* including nasal-to-temporal* central-toperipheral* and inferior-to-superior gradients of progressively less choriocapillary filling delay. )he D$CC correlated with the location* num"er* si1e* confluence* and fluorescein staining characteristics of the associated drusen. Conclusion. D$CC occurs in some eyes with A,$D. )his finding may not only assist in defining eyes at risk for progressive disease "ut may also help to elucidate the pathogenesis of age-related macular degeneration.

Cystoid macular degeneration in experimental "ranch retinal vein occlusion Dallow 6.&.=.5 Danis ,.3.5 +indley C.5 %eider $. Department of /phthalmology* 7niversity of Disconsin 'chool of $edicine /phthalmology (899 /ct58G-(I.:(;F(-8 $acular edema and collateral vessels were examined clinically and histopathologically up to :9 months after "ranch retinal vein occlusion in six eyes of five cynomolgus monkeys. 6n all six* central macular swelling and fluorescein leakage from the retinal vasculature were confined to the acute stage. &owever* histopathologically* at the chronic stage* only two maculas were completely recovered and unremarka"le* whereas the other four showed varia"le degrees of cystoid degeneration and photoreceptor cell loss. 6n the two recovered maculas* six to eight normal-si1ed capillaries separated the fovea from the nearest cluster of capillary collaterals. 6n three maculas with cystic degeneration* collaterals incorporated the circumfoveal capillaries. 6n the fourth macula with cystic degeneration* collaterals were separated from the center "y two normal-si1ed capillaries "ut were also associated with large areas of capillary nonperfusion partially due to occlusion of the macular arteriole.

)he clinical picture of retinal throm"osis %iesel 3. 7niv.-Augenklin.* +ern 'wit1erland Blin $onats"l Augenheilkd (8FF Ce"5(FI-4.:(9<-84 +esides acute arterial occlusion and simple venous throm"osis* the clinical symptomatology may include signs of chronic arterial insufficiency* i.e. progressive "lurring of vision* a"solute visual field defects* cotton wool exudates* capillary occlusion and increased retinal circulation time. )he poor visual prognosis is caused "y progressive macular degeneration. 6n the case of acute arterial throm"osis* fragmentation of the "lood column and a"sence of arterial pulsation are indicative of pronounced retinal ischemia. )he ophthalmoscopic aspect of a visi"le em"olus may "e a hint for the prognosis of eventual recanalisation.

[7indings of fluorescence angiography studies of the posterior eye pole] +aurmann &. +er 2usammenkunft Dtsch /phthalmol es (8FG5-F;.:G<-8 )he main findings during fluorescence angiography of the macular area are classified on the "asis of topographic points of view. $acular changes are schematically presented in G stages: vitreoretinal "oundary area5 puckering syndrome5 retinal circulation5 perimacular capillary changes5 sensory epithelium5 not visuali1ed in the angiogram5 pigment epithelium and +ruch0s mem"rane5 central retinal detachment5 deposits in the macular area5 macular degeneration* secondary maculopathies5 haemorrhages "elow the pigment epithelium5 disorders of the pigment epithelium5 +ruch0s mem"rane and other levels -inflammations* scars* macular defects.5 choroid5 folds* scars* atrophies* tumors.

)he evoked cortical potential in macular degeneration /rpin E.A.5 /rpin !.5 $cCulloch C. Dept. /phthalmol.* 7niv. )oronto Canada E Am eriatr 'oc (8F: Dec544-(4.:G;<-F $acular degeneration causes a profound loss of visual acuity due to inade@uate "lood circulation in the capillaries of the choroid plexus and pigment epithelium of the important pattern recogni1ing area of the retina. )his disease is the cause of half the "lindness in people over the age of <G* and of nearly one third of all "lindness. 6n this study* an important new techni@ue was added to < tests already in use* to assess retinal disease. Data on (I patients were collected "y the following methods: optic disc photography5 fluorescein angiography5 visual acuity testing5 visual fields5 foveal sensitivity5 electroretinography with automatic analysis of the record "y use of an electronic sampling filter and a specially "uilt computer to measure the total electrochemical energy released "y the retina5 and the evoked cortical response -as indicated in the electroencephalogram. to the stimulus of an alternating chess "oard pattern. )his new techni@ue tests the total system for visual pattern recognition. )he results indicate that the evoked cortical response is the "est o"Aective test of visual acuity.

)he development of neovasculari1ation of senile disciform macular degeneration )eeters >.D.5 +ird A.C. 6nst. /phthalmol.* =ondon 7nited Bingdom Am E /phthalmol (8F; Eul5F<-(.:(-(9

%inety five eyes with senile disciform macular degeneration were evaluated for the presence of neovasculari1ation* using "iomicroscopy and fluorescein angiography. )he disciform lesions were classed as avascular* neovascular* and advanced cicatricial. Cour to 4F mth later these disciform lesions were reassessed. At that time* <FH of the initially avascular disciform lesions had developed new "lood vessels in the su"pigment epithelial vessels and (4H of fellow eyes with drusen and pigment epithelial changes had developed disciform processes. )he patterns of neovasculari1ation o"served on follow up examination conformed to two general types: early vascular patterns usually with a capillary plexus in the su"macular position* and advanced vascular patterns consisting of large vessels seen with the "iomicroscope supplying a plexus of capillaries usually eccentric to the macula. 6n the early lesions* the neovascular complexes demonstrated marked growth* fre@uently with development of eccentric capillaries and large vessels. =esions initially with large vessels demonstrated slower growth* and in general the large vessel was considered a sign of maturity of the lesion. )reatment of the neovascular disciform lesion should "e directed to the capillary plexus which is responsi"le for exudation and "leeding with secondary detachment of the macula.