Diabetic Retinopathy Ocular Diseases

organs,฀including฀the฀vascular฀wall,฀kidneys฀and฀retina฀ [143] .฀Recent฀research฀indicates฀ that฀smoking฀inluences฀these฀glycation฀processes฀ [143] . An฀older฀study฀in฀a฀sample฀of฀181฀diabetic฀patients฀with฀diabetic฀retinopathy฀already฀ showed฀that฀the฀progression฀of฀the฀disease฀in฀smokers฀increases฀as฀a฀function฀of฀pack-years฀ of฀smoking฀and฀the฀duration฀of฀diabetes฀ [144,฀145] ,฀with฀prevalence฀among฀men฀reportedly฀ being฀higher฀than฀among฀women฀ [145,฀146] .฀This฀association฀has฀not฀been฀conirmed฀in฀ studies฀involving฀larger฀number฀of฀patients฀ [147–149] .฀Instead,฀it฀is฀believed฀that฀the฀for- mation฀of฀glycohaemoglobin฀as฀a฀result฀of฀smoking฀tends฀to฀encourage฀nephropathy฀rather฀ than฀retinopathy฀ [148,฀150] .฀Elsewhere,฀an฀association฀was฀suspected฀only฀in฀men฀with฀a฀ younger฀onset฀of฀disease฀ [151] ,฀or฀the฀relations฀between฀cigarette฀smoking฀and฀retinopathy฀ or฀nephropathy฀were฀variable฀depending฀on฀the฀statistical฀models฀used฀ [152] .฀The฀recently฀ published฀EURODIAB฀IDDM฀Complications฀Study฀also฀found฀an฀increased฀risk฀for฀the฀ development฀of฀diabetic฀retinopathy฀in฀smokers฀only฀where฀there฀was฀an฀early฀onset฀of฀ IDDM฀together฀with฀a฀genetic฀component฀for฀hypertension฀ [153] .

7.2.2 Cataract and Lens Opacity

The฀ 86 rubidium฀eflux฀technique฀rubidium฀is฀a฀mimic฀of฀potassium฀has฀been฀used฀in฀ani- mal฀experiments฀to฀study฀the฀inluence฀of฀tobacco฀smoke฀on฀cultured฀rat฀lenses,฀which฀are฀ metabolically฀active฀and฀have฀functional฀defence฀systems.฀It฀was฀found฀that฀the฀smoke฀ particles฀are฀actively฀transported฀into฀the฀lens฀and฀are฀not฀absorbed฀as฀a฀result฀of฀increased฀ permeability;฀ histologically,฀ the฀ lenses฀ also฀ exhibited฀ morphological฀ changes฀ such฀ as฀ hyperplasia,฀hypertrophy฀and฀multi-layering฀of฀epithelial฀cells฀ [154] .฀In฀addition,฀the฀heavy฀ metals฀copper,฀lead฀and฀cadmium฀inhaled฀from฀cigarette฀smoke฀accumulate฀in฀the฀lens฀and฀ are฀possibly฀involved฀in฀cataract฀development฀ [155] .฀Moreover,฀the฀inhaled฀nitrous฀gases฀ and฀NO,฀which฀accumulate฀in฀the฀anterior฀chamber฀during฀ocular฀inlammation,฀lead฀to฀ changes฀in฀a-crystallin฀indicative฀of฀oxidative฀damage฀which฀show฀up฀as฀increased฀luo- rescence฀ l -kynurenine฀may฀be฀an฀intermediate฀causative฀agent฀ [156] . A฀clinical฀study฀in฀838฀watermen฀investigated฀the฀occurrence฀of฀nuclear฀or฀cortical฀lens฀ opacities,฀and฀a฀dose-dependent฀association฀was฀found฀in฀smokers฀between฀nuclear฀opacity฀ and฀pack-years฀of฀smoking฀ [157] ,฀a฀inding฀that฀has฀been฀conirmed฀in฀other฀studies฀ [149,฀ 158–160] .฀These฀lens฀opacities฀regressed฀partially฀on฀smoking฀cessation฀ [157] .฀A฀10-year฀ prospective฀study฀in฀17,824฀physicians,฀in฀whom฀557฀incident฀cataracts฀were฀conirmed฀ during฀5฀years฀of฀follow-up,฀demonstrated฀that฀the฀risk฀of฀cataract฀in฀heavy฀smokers฀20฀ cigarettesday฀was฀doubled฀compared฀with฀never-smokers฀RR฀=฀2.16;฀CI:฀1.46–3.20,฀ with฀nuclear฀sclerotic฀changes฀being฀observed฀in฀particular฀RR฀=฀2.24;฀CI:฀1.47–3.41฀ [161] .฀Past฀smokers฀had฀an฀elevated฀risk฀of฀posterior฀subcapsular฀cataract฀RR฀=฀1.44,฀ whereas฀ current฀ smokers฀ of฀ 20฀ cigarettesday฀ did฀ not฀ have฀ an฀ increased฀ cataract฀ risk฀ [161] .฀The฀association฀between฀pipe฀smoking฀and฀nuclear฀cataract฀OR฀=฀3.1;฀CI:฀1.5–8.2฀ was฀stronger฀than฀the฀association฀with฀cigarette฀฀smoking ฀[162] . Additional฀ moderate฀ alcohol฀ intake฀ £4฀ drinksday฀ lowered฀ cataract฀ prevalence,฀ whereas฀heavy฀alcohol฀consumption฀potentiated฀the฀effects฀of฀cigarette฀smoking฀OR฀com- pared฀with฀non-drinkers฀=฀3.9;฀CI:฀0.9–16.6฀ [162,฀163] .฀The฀incidence฀of฀cataracts฀in฀ diabetic฀patients฀was฀not฀signiicantly฀affected฀by฀additional฀smoking฀ [164] .฀Cataract฀oper- ations฀lens฀nucleus฀extraction฀in฀female฀smokers฀were฀associated฀with฀a฀risk฀of฀more฀ frequent฀complications฀ [165] .

7.2.3 Graves’ Ophthalmopathy

Graves’฀ophthalmopathy,฀a฀condition฀commonly฀encountered฀in฀hyperthyroidism,฀is฀criti- cally฀inluenced฀by฀the฀release฀of฀interleukin-1฀IL-1฀ [166] ,฀and฀smoking฀is฀known฀to฀ increase฀the฀production฀of฀IL-1,฀and฀of฀IFN-g฀and฀TNF-a฀ [166,฀167] . The฀increased฀risk฀for฀Graves’฀ophthalmopathy฀associated฀with฀cigarette฀smoking฀is฀2.4฀ CI:฀1.12–5.18,฀and฀Europeans฀have฀a฀substantially฀greater฀risk฀of฀developing฀this฀compli- cation฀than฀have฀Asians฀ [168] .฀These฀results฀are฀conirmed฀by฀a฀study฀conducted฀in฀Taiwan฀ [169] .฀Cigarette฀smoking฀also฀encourages฀the฀progression฀of฀the฀disease,฀and฀the฀effective- ness฀of฀radiotherapy฀and฀of฀glucocorticoids฀is฀reduced฀ [170] .

7.2.4 Macular Degeneration

Age-related฀macular฀degeneration฀causes฀blindness฀in฀thousands฀of฀patients,฀particularly฀in฀ the฀USA,฀and฀the฀medical฀treatment฀options฀are฀limited฀at฀best฀ [171] . It฀is฀therefore฀understandable฀that฀several฀studies฀have฀attempted฀to฀establish฀an฀asso- ciation฀with฀cigarette฀smoking.฀One฀meta-analysis฀assessed฀data฀from฀three฀studies฀con- ducted฀ in฀ 14,752฀ patients฀ with฀ age-related฀ macular฀ degeneration.฀ Since฀ the฀ population฀ originated฀from฀three฀continents,฀there฀were฀geographical฀differences฀but฀no฀gender฀differ- ences฀in฀disease฀prevalence฀ [172] .฀This฀study฀also฀clearly฀showed฀the฀harmful฀effects฀of฀ smoking฀in฀terms฀of฀the฀development฀of฀macular฀degeneration฀ [172] . The฀risk฀for฀macular฀degeneration฀has฀been฀shown฀to฀be฀associated฀with฀cigarette฀smok- ing฀ and฀ raised฀ serum฀ cholesterol฀ levels฀ [173] .฀ Compared฀ with฀ ex-smokers฀ or฀ never-฀ smokers,฀ the฀ relative฀ odds฀ for฀ age-related฀ macular฀ degeneration฀ in฀ females฀ who฀ were฀ current฀smokers฀has฀been฀reported฀as฀2.50฀95฀CI:฀1.01–6.20;฀for฀males฀it฀was฀3.29฀ 95฀CI:฀1.03–10.50.฀In฀both฀cases,฀the฀exudative฀form฀predominated฀ [174] .฀Macular฀ pigment฀density฀in฀smokers฀was฀substantially฀reduced฀compared฀with฀that฀in฀non-smokers฀ 0.16฀vs.฀0.34;฀p฀฀0.0001;฀an฀inverse฀correlation฀was฀identiied฀between฀macular฀pigment฀ density฀and฀pack-years฀of฀smoking฀ [175] .฀Investigations฀in฀6,174฀persons,฀55฀years฀and฀ older,฀have฀also฀shown฀that,฀compared฀with฀non-smokers,฀the฀risk฀for฀age-related฀macular฀ degeneration฀is฀increased฀6.6-fold฀in฀current฀smokers฀10฀pack-years฀of฀smoking฀and฀ 3.2-fold฀ in฀ ex-smokers.฀ Arteriosclerotic฀ changes฀ did฀ not฀ alter฀ the฀ association฀ between฀ smoking฀and฀macular฀degeneration฀ [176] .฀Among฀women฀who฀currently฀smoked฀the฀rela- tive฀risk฀for฀macular฀degeneration฀was฀2.4฀compared฀with฀women฀who฀had฀never฀smoked฀ [177] ,฀although฀the฀association฀was฀less฀strong฀than฀in฀men฀ [178] .฀It฀should฀be฀emphasised฀ that฀the฀risk฀for฀macular฀degeneration฀increases฀dramatically฀above฀a฀consumption฀of฀20฀ cigarettesday฀ [179] ฀ and฀ that฀ neovascularisation฀ has฀ been฀ detected฀ in฀ addition฀ [180] .฀