Biometry of the crystalline lens in late onset diabetes:

Transcription

1 428 Nuffield Lbortory of Ophthlmology, University of Oxford J M Sprrow J ron N Phelps rown Deprtment of Public Helth nd Primry Cre, University of Oxford H W Neil Correspondence to: Dr John M Sprrow, Deprtment of Ophthlmology, University of Leicester, The Leicester Royl nfirmry, Leicester L1 5WW. ccepted for publiction 12 December 1991 ritish Journl ofophthlmology, 1992,76, iometry of the crystlline lens in lte onset dibetes: the importnce of dibetic type John M Sprrow, nthony J ron, Nichols Phelps rown, H W Neil bstrct Lenticulr nd nterior chmber biometry were studied in non-ctrctous eyes by mens of Scheimpflug photogrphy nd digitl imge nlysis. The study popultion consisted of 91 lte onset dibetic subjects nd 115 nondibetic nteroposterior xil lens thickness, corticl thickness, nucler thickness, nterior cler zone thickness, nterior chmber depth, nd nterior nd posterior lenticulr curvtures were ssessed. ge plyed n importnt role in determining lens biometry in ll subjects, nd smll but significnt differences were found between lte onset dibetics nd non-dibetics. n the lte onset dibetic subgroup, prt from ge, dibetic retinopthy ws the only significnt prmeter found which determined lens biometry. These biometric findings in lte onset dibetes re in mrked contrst to the lrge overll effect of dibetes nd the powerful effect of dibetic durtion which we previously reported in erly onset dibetes. Further nlysis of the dt from our previous study hs been provided, which clerly demonstrtes differences between the impct of erly nd lte onset dibetes on the biometry of the nterior oculr segment. Mitotic ctivity in the pre-equtoril lenticulr epithelium results in stedy growth of the humn crystlline lens throughout life.'-5 Overll lens growth is determined by dynmic blnce between externl ccretion of secondry lens fibres nd the centrl compction of older nucler or perinucler fibres.36 nteroposterior lens growth is proportionlly greter thn equtoril growth, nterior nd posterior lens curvtures therefore become steeper (shorter rdii of curvture) with incresing ge.5 7 Lenticulr biometry is disturbed in dibetes,58-1 with erly onset dibetics showing mrkedly bnorml lens growth with powerful dependency upon dibetic durtion.5 The nterior cler zone (first zone of disjunction) of the lens behves independently of the other lenticulr zones. This zone, which is neither ge dependent nor dependent upon dibetic durtion, hs been found to be mrkedly incresed in erly onset dibetics.5 The incresed nterior cler zone thickness nd the powerful dependency of other biometric prmeters on dibetic durtion imply tht the lenses of erly onset dibetics my not simply be over-hydrted, but tht they my be in stte of ccelerted growth, with either more (hyperplstic mechnism) or individully lrger (hypertrophic mechnism) secondry lens fibres being formed. ntrcellulr 'swelling' of individul lens fibres would be theoreticlly possible lthough such swelling would need to be confined to the newly formed (metboliclly ctive) fibres to be comptible with the powerful durtion effect observed in erly onset dibetes.5 n order for extrcellulr swelling of the lens to explin the observed effect of durtion it would be necessry to postulte tht such swelling incresed over time with dibetic durtion. This is conceivble, s ongoing cumultive dmge to membrne structures could tke plce over periods of yers. Previous studies hve not exmined specificlly the effect of lte onset dibetes on lenticulr biometry.5"9 ' The present study exmines biometry in cler lenses of lte onset dibetics nd controls, nd drws comprisons between the impct of dibetes on the lens in lte nd erly onset dibetes. Mteril nd methods SUJCTS totl of 91 lte onset dibetics (57 mles) nd 115 non-dibetic controls (64 mles) were included in the study. These ptients formed prt of popultion-bsed comprtive lens study." The dibetics were survivors of the Oxford Community Dibetes Study,'2 nd community-bsed controls were selected to group mtch the dibetics by ge nd sex. n the present study only the lte onset dibetics were included. Lte onset dibetics were regrded simply s ll those dibetics who did not fit the inclusion criteri used in our erlier study for erly onset dibetes. n effect this ment tht lte onset dibetics were defined s ny dibetic whose ge t onset ws more thn 3 yers regrdless of the type of dibetic tretment, or dibetics whose ge t onset ws 3 yers or less, but who did not require continuous insulin tretment. Controls were ll community bsed, nd were ccepted if they hd no history of dibetes or impired glucose tolernce, nd non-fsting whole venous blood glucose of less thn 7-8 mmol.'3 14 ndividul eyes of dibetics nd controls were included in the present study if the lenses were non-ctrctous, nd hd norml nterior oculr segments nd vision sufficiently good to hold fixtion during Scheimpflug photogrphy. Ctrctous lenses were excluded becuse such lenses my hve bnorml biometry, lthough certin minor opcities s defined by the Oxford Clinicl Ctrct Clssifiction nd Grding System'7 18 were ccepted: nucler brunescence nd white nucler sctter up to nd including Grde 2, spoke opcities nd wterclefts ofgrde 1, nd isolted vcuoles, retrodots nd focl dots. No nterior or posterior sub- r J Ophthlmol: first published s /bjo on 1 July Downloded from on 15 September 218 by guest. Protected by copyright.

2 iometry ofthe crystlline lens in lte onset dibetes: the importnce ofdibetic type Figure Frequency distribution ofthe ges oflte onset dibetics (cses) nd non-dibetics (controls). 4 - _ T Dibetics (n = 91) Controls (n = 115) ) C.) en ) Q,. z cpsulr opcities were permitted, s subcpsulr opcities were specificlly known to be ssocited with reduced lens size.'5 There were thus totl of 378 eligible eyes in 26 subjects; 188 were right eyes nd 19 were left eyes. The study ws pproved by the Centrl Oxford Reserch thics Committee (ref no 1211), nd informed consent ws obtined from prticipnts. PROCDUR The procedure followed hs been described.5 riefly, subjects were contcted nd recruited by the primry investigtor (JS). Following short history nd Snellen cuity testing pupils were dilted (tropicmide 1% nd phenylephrine 1%) with due regrd to the usul precutions. Lenses were ssessed for ctrct t the slit-lmp biomicroscope, nd Scheimpflug photogrphs were tken using rown Scheimpflug cmer.'921 iometric mesurements on digitised imges were performed by msked observer (JS) using the Oxford Modulr Ctrct mge nlysis System which ws developed by the uthors.22 s in our previous study of lens biometry in erly onset dibetes5 the biometric prmeters mesured were: nteroposterior xil lens thickness, corticl thickness, nucler thickness, nterior cler zone thickness, nterior chmber depth, nd nterior nd posterior lenticulr curvtures. Corticl thickness ws derived rithmeticlly s the difference between lens nd nucler thickness. STTSTCL MTHODS iometric mesurements were in generl obtined from both eyes, lthough certin ptients contributed mesurements on only one eye. preliminry nlysis ws performed by plotting the biometric dt ginst ge nd performing simple liner regression for the dibetic nd non-dibetic groups seprtely. n the min nlysis the within-subject intereye correltion ws ccounted for by employing the intrclss correltion model of Rosner for clculting significnce levels nd confidence intervls The dependent vribles were continuous nd were pproximtely normlly distributed. The min nlysis took the form of ge multiple liner regression nlysis with groups (fctors), the biometric mesures being used s dependent vribles in series of model fitting exercises. djustment for minor imblnces in the cse/control ge distribution ws chieved by treting ge s covrite in the relevnt nlyses. To fcilitte comprison with our erlier study of lens biometry in erly onset dibetes the nlyses were performed in brodly the sme mnner s in tht study.5 (The orders of the fitting of terms to the models re indicted in the tbles.) Using the dt from the previous study s well s the dt from the present study dditionl nlyses were performed compring the overll effects of erly nd lte onset dibetes with non-dibetic controls, nd compring erly nd lte onset dibetics directly. These nlyses provide the verge group differences (with 95% confidence intervls) between both types of dibetics nd controls, nd between erly nd lte onset dibetics, fter tking ccount of the (confounding) effects ofge nd sex. The nlysis ws performed using the Generlised Liner nterctive Modelling (GLM) System of the Numericl lgorithms Group (NG, Wilkinson House, Jordn Hill Rod, Oxford OX2 8DR). Results The ge distribution of the lte onset dibetics nd controls is presented in Figure 1. The ge/ durtion distributions for the dibetics lone re presented in Tble 1. Figures 2 to 8 illustrte the preliminry regression nlyses of biometry ginst ge. These grphs demonstrte the importnt effect of ge on nterior segment biometry. For certin of the biometric fetures studied there pper to be smll differences between the lte onset dibetics nd These impressions were investigted in the forml nlysis summrised in Tble 2. The 'lte onset dibetics nd controls' nlysis (26 subjects, 378 eyes) confirmed tht ge ws n importnt determinnt of biometry. Modest differences existed between dibetics nd nondibetics for xil lens thickness, corticl thickness, nd front rdius of curvture. These chnges were such tht lenses of dibetics were 'thicker' with steeper front curvtures. The significnt ge by dibetic sttus interction term (ge.st) for front rdius of curvture indicted tht the younger dibetics were reltively more ffected, this being well demonstrted in Figure 7 (regression lines non-prllel). substntil difference in nterior cler zone thickness between dibetics nd non-dibetics ws found, with dibetics hving incresed cler zone thick- Tble ge by dibetic durtion ofthe lte onset dibetes study popultion Dibetic durtion (yers) loto 2to ge (yers) <1 <2 <3 3+ Totl 3 to < to < to < to < to < Totl r J Ophthlmol: first published s /bjo on 1 July Downloded from on 15 September 218 by guest. Protected by copyright.

3 43 ( c : ) 5. U) ) x 4. o ness. Femle sex ws ssocited with decresed corticl thickness. n the lte onset dibetic subgroup (91 subjects, 161 eyes) ge ws n importnt determinnt of lens biometry for ll prmeters except nucler thickness nd nterior cler zone * Dibetics (-) o Controls ( ). L ge (yers) Figure 2 Plot ofnteroposterior xil lens thickness derivedfrom imge nlysis of Scheimpflug photogrphs ginst ge. Seprte liner regression linesfor dibetics nd 5 T 4. mm 3 - ) 2-._1 U - li 1- * * Dibetics (- ) Controls (- ) t tf ge (yers) Figure 3 Plot ofnteroposterior corticl thickness ofthe lens derivedfrom imge nly Scheimpflug photogrphs ginst ge. Seprte liner regression lines for dibetics nd 4 Dibetics Controls ( ).N i U i ge (yers) Figure 4 Plot ofnteroposterior nucler size of the lens derived from imge nlysis of Scheimpflug photogrphs ginst ge. Seprte liner regression lines for dibetics nd Sprrow, ron, Phelps rown, Neil thickness. Prolifertive dibetic retinopthy ws ssocited with incresed lens nd corticl thickness. Dibetic durtion, sex, or type of dibetic tretment (insulin, orl hypoglycemics, or diet) did not hve demonstrble effect on ny of the biometric prmeters studied. mong the controls (115 subjects, 217 eyes) ge ws n importnt determinnt of biometry, with femle sex ssocited with decresed xil length nd corticl thickness nd with incresed nucler thickness. The differences between the lte onset dibetics nd controls were observed to be less impressive thn those previously found for 153 erly onset dibetics nd 153 controls5 (the 115 controls in the present study being subset of the previous 153). For this reson further nlyses mking direct comprison between erly nd lte onset dibetics were performed. The first of these nlyses is summrised in Tble 3, nd demonstrted importnt differences between the two groups of dibetics (fter ccounting for confounding effects). The differences between the erly nd lte onset groups were such tht the lenses of the erly onset ptients were significntly lrger in their xil, corticl, nd nucler thicknesses, hd steeper front nd bck rdii of curvtures, nd were ssocited with shllower nterior chmbers. The interction terms between ge nd type of dibetes (ge.type) indicted certin differences in the slopes of the regression lines between the two groups. The regression lines for lens thickness (corticl thickness) nd front rdius of curvture were ech less steep in the lte onset dibetics thn in the erly onset dibetics, indicting tht the verge chnge per yer in biometry ws greter in the erly onset group. The mgnitudes of the observed effects (with 95% confidence intervls) re presented in Tble 4. These nlyses demonstrted the verge effects of lte onset nd erly onset dibetes on lens biometry compred with controls, nd lso compred erly nd lte onset dibetics directly. fter djustment for ge nd sex, the effect sizes in the erly nd lte onset dibetics compred with controls indicted tht the impct of lens biometry of erly onset dibetes ws between two nd three times tht found in lte onset dibetes. The finl group of nlyses in Tble 4 provide direct estimtes (djusted for ge nd sex) for the overll differences between erly nd lte onset dibetics. These estimtes show tht dibetics demonstrte prticulr pttern of disturbnce of nterior segment biometry, nd tht the mgnitude of this disturbnce is considerbly greter mong erly onset thn mong lte onset dibetics. ecuse the erly onset dibetics from our previous study' were on verge younger thn the lte onset dibetics in the present study, two further nlyses were performed to determine whether the observed differences might be due to differences in the ge structures of the two dibetic popultions. To exmine this point ttention ws directed to the impct of dibetic durtion, which, s hs been noted bove, ws powerful effect mong the erly onset dibetics,5 but which ppered to ply no role in the lte onset dibetics. Firstly, the erly onset group r J Ophthlmol: first published s /bjo on 1 July Downloded from on 15 September 218 by guest. Protected by copyright.

4 iometry ofthe crystlline lens in lte onset dibetes: the importnce ofdibetic type T- - n.-1 U-. T1 c 2 Co - *1._ * ws exmined to determine whether the powerful durtion effect persisted cross the entire ge rnge. For this the erly onset dibetics (ge rnge 1 to 74 yers) were grouped into ge qurtiles. The durtion effect for the biometric Dibetics ( ) o Controls (.-4 U " M &&glu M -. r-l* - - omo..n._ s-_ W ooo o * " M D, * o o prmeters ws then determined seprtely for ech ge qurtile in model which pre-fixed the ge effect to tht of the non-dibetic control group, nd mintined constnt y-intercept for the ge qurtiles. summry of this nlysis ppers in Tble 5, which gives the durtion estimtes (nd 95% confidence intervls) for ech qurtile. This nlysis demonstrted tht in generl the durtion effect mong the erly onset dibetics persisted cross ll the ge qurtiles. n the second nlysis ll the dibetics (erly nd lte onset) were grouped in deciles ccording to their ge t onset of dibetes. This pproch dispensed with the prior clssifiction of the dibetes into erly nd lte onset groups. fter djusting for ge nd sex ech 'onset decile' group ws exmined seprtely for n effect of dibetic durtion (Tble 6). These nlyses demonstrted tht for most prmeters the effect of dibetic durtion on biometry diminished drmticlly when ge t onset of dibetes exceeded 3 yers g (yers Figure 5 Plot ofnterior cler zone th; ickness ofthe lens derivedfrom imge nlysis of Scheimpflug photogrphs ginst ge. Seprte liner regression lines for dibetics nd Discussion The results of this study hve demonstrted 5 T 4' P -o CD3 C. + 2, U c o o importnt differences in the impct of lte onset nd erly onset dibetes on the biometry of the Dibetics ( ) nterior oculr segment. The impct of lte onset Controls (- ) dibetes on biometry ws modest, nd direct comprison between erly onset nd lte onset dibetics confirmed these biometric differences o between the two groups of dibetics. Como * prisons between ech dibetic type nd nono o dibetic controls reveled tht the impct on ;3. biometry of erly onset dibetes ws two to three >. times greter thn the impct of lte onset _ 8 ;t g dibetes. Furthermore, within the dibetic sub- &, groups, no effect of dibetic durtion ws found T * mong the lte onset dibetics, which ws in ' mrked contrst to the powerful effect of dibetic L durtion previously found in erly onset dibetes.5 Further nlysis of the dt from our 1 erlier study hs demonstrted tht the durtion effect in erly onset dibetes persists cross ll ge (yers) the ge qurtiles (ge rnge 1 to 74 yers). The Figure 6 Plot ofxil nterior chmbder depth ofthe eye derivedfrom imge nlysis of demonstrtion tht the durtion effect persists Scheimpflug photogrphs ginst ge. S'eprte liner regression linesfor dibetics nd 1-( co C.) C - 1o - 4),o o -U cross the ge qurtiles is importnt, becuse it illustrtes tht the bsence of durtion effect in the lte onset dibetics cnnot be ttributed to Dibetics ( ) the fct tht the lte onset dibetics were on o Controls(--) verge older thn the erly onset dibetics. When the clssifiction of dibetics into erly nd lte onset subjects ws dispensed with, ge t o onset of more thn 3 yers ws noted to be 9 g ssocited with mrked reduction in the effect :> * Jgi n nof dibetic durtion fter djustment for the ^- p-3 qi ^ effects of sex nd geing. These findings support --69 D the ide tht the response of the lens to erly onset dibetes is distinct, nd is not simply *t. w.4n Q s function of the ge of the ffected individul. t Ạ my be rgued tht the filure to demonstrte n effect of dibetic durtion in the lte onset dibetics could be due to the fct tht disese durtion is frequently not precisely known in ' such ptients. The disese durtion of such ge (yers) ptients however would in generl be under- ofthe lens derived from imge nlysis of Figure 7 Plot offront rdius ofcurvtzire estimted nd this would tend to mplify ny Scheimpflug photogrphs ginst ge. Seeprte liner regression lines for dibetics nd ctul ssocition with durtion. Our filure to identify ny ssocition with disese durtion in r J Ophthlmol: first published s /bjo on 1 July Downloded from on 15 September 218 by guest. Protected by copyright.

5 432 ~~~~~~~~~~~~~~~~~~~~~~~~~~Sprrow, ron, Phelps rown, Neil V3 1 U) 15-5 % Dibetics (~ Controls (---) ge (yers) tht ny durtion effect mong the lte onset Figure 8 Plot ofbck rdius ofcurvture ofthe lens derived from imge ntilysis of dibetics would hve hd to be smll (nd Scheimpflug photogrphs ginst ge. Seprte liner regression lines for dil5etics nd therefore of doubtful importnce) to hve been missed. Tble 2 Summry ofp vlues from nlysis of lens dimensions in lte onset dibetes nd Our definitions of erly onset dibetes s controls (cler lenses) Lens Cortex Nucleus CZ C F. Lte onset dibetics nd controls (subjects=26, eyes= 378, right= 188, left= 19) ge «lw 'z< <W < St NS -49 NS -i ge.st NS NS NS NS NS NS Sex NS -2 NS NS NS N R for model i Lte onset dibetes (subjects=91, eyes= 161, right=81, left=8) ge <1-6 <1-6 NS NS -1-1 Dur NS NS NS NS NS N Sex NS NS NS NS NS N Tret NS NS NS NS NS N GR NS NS NS NS NS Ns PLR NS NS NS N R for model Controls (subjects= 1 15, eyes=217, right= 17, left= 11) ge «<1-6 «< <W < Sex NS NS NS NS 1 R for model CZ=nterior cler zone thickness of lens; C=nterior chmber depth; FR=fro)nt rdius of curvture of lens; K=bck rdius of curvture of lens; St=dibetic or non-dib4etic sttus; Dur=dibetic durtion; Tret=dibetic tretment (diet, orl hypoglycemic or in; GR=bckground retinopthy; PLR=prolifertive retinopthy; p vlues clcult4 correltion model of Rosner.24 Tble 3 Summry ofp vlues from nlysis oflens dimensions in erly nd (cler lenses) Lens Cortex Nucleus CZ C F] rly nd lte onset dibetics (subjects=244, eyes=456, right=229; left=227) ge <<l-6 «16-33 NS «1-- «< Sex NS NS NS NS NS N. Type <W NS -1 -( ge.type -39 NS -52 NS NS - R for model ( CZ=nterior cler zone thickness of lens; C=nterior chmber depth; FR=fro] nt rdius of curvture of lens; K=bck rdius of curvture of lens; Type=type of dibetes (e p vlues clculted by-the intrclss correltion model of Rosner.2314 Tble 4 Comprison ofthe overll effects (±95% C) ofdibetes on lens bio between controls nd dibetics (lte nd erly onset seprtely), nd between e),rly nd lte onset dibetics, fter ccountingfor the (confounding) effects ofge nd sex (non-seql Lens Cortex Nucleus CZ C l lte onset ptients is therefore unlikely to rise from inccurte knowledge of true dibetic durtion mong lte onset dibetics. The sttisticl power of this study to detect 'medium' sized durtion effect mong the lte onset dibetics in multiple regression nlysis (13% of the vrince by Cohen's convention) t the 5% probbility level for 91 subjects is 87%, nd for 161 eyes is 99%.25 The true power of the study s nlysed by the intrclss correltion 3 ~~~model2324 will therefore lie between these upper nd lower limits, depending on the ctul withinsubject intereye correltion for ech prmeter under study. ven if the intereye correltion ws high it would be resonble to suppose tht the.~... power of this study to detect medium size effect 3 9 t the 5% level is t lest 9%, which confirms dibetes dignosed t or before 3 yers of ge R K nd requiring continuous insulin tretment, nd lte onset dibetes s ll other dibetics hve the 1--6 <1-6 effect of seprting off group of young subjects 17 NS woms etil ye1dee.ti yedee.ti s NS definition of Type 1 dibetes, lthough bsed,6-43 purely on clinicl fetures nd ge t onset, hs been used extensively in epidemiologicl 2 3 studies.27 prospective study of 268 newly s NS dignosed dibetic ptients clssified on the S NS bsis of clinicl criteri only found tht ll NS s NS ptients dignosed before the ge of 4 yers who were cliniclly ssessed s insulin-dependent, hd fsting C-peptide levels 18 months fter 1W <1o-, dignosis which were dignostic of insulin dependence.2 The clssifiction tht we used will therefore hve ensured tht erly onset ptients were correctly chrcterised s hving sulin); miniml endogenous insulin production, ed by the intrclss lthough the lte onset group is likely to hve contined smll number of misclssified lte onset dibetes ptients with true Type 1 (insulin-dependent) dibetes. This might confound comprisons R K between the erly nd lte onset groups, nd it is conceivble (lthough unlikely) tht the 'wek' lw <W effects of dibetes seen in our lte onset group re S NS (prtly) due to the misclssifiction nd inclusion 21 NS of smll number of truly Type 1 dibetics within group which should idelly contin only Type 2 ptients. Thirty (33%) of the lte onset irly or lte onset); dibetics were using insulin t the time of the study, 15 (16%) hving hd their dibetes dig- )metry (mm) nosed t ge <5 yers, nd 1(11%) t ge <4 yers. The number of potentil misclssifictions ruentil nlysis) ws therefore not very gret. K n the present study prolifertive dibetic Lte onset 12* -11* -3.26* ( ).7l-22 retinopthy ws found to be ssocited with vscontrols (--93) (-91) (-42) (-12) (11) (- 39)1-39)(-23) -23) greter lens nd corticl thickness, n effect (n=26) which is in generl consistent with our previous rly onset -37t -28t-.99* -49t [ vscontrols (-89) (-84) (-4) (-11) (-1) (- finding in erly onset -45) dibetics of incresed cler (-21) \-/ (n= 36) rly vs -43t-.31*.11* * 1.32* zone nd nucler thickness, nd steeper front lte onset (-14) (-13) (-59) (-19) (-15) (.-62) (-33) -.62* nd bck curvtures in ptients with retinopthy (n=244) (confounding vribles ccounted for in ech CZ=nterior cler zone thickness of lens; C=nterior chmber depth; FR=fror study). These ssocitions rise the possibility ntrdus of curvture of lens; K=bck rdius of curvture of lens; 95% C=95% confidence i * =p<o5;,ntervdiuo tht disturbnces in lens biometry could be due t = p< 14; confidence intervls nd p vlues clculted by the intrcls: ;scorreltion to the forwrd diffusion of n (ngiogenic) model of Rosner2' 24; ±ve vlues indicte tht the prmeter is greter in dibetics cf( two nlyses, nd tht the prmeter is greter in erly onset dibetics cf lte onset d. ibeticls in the 3irst growth fctor from the posterior oculr segment, nlysis. or they my simply imply tht ptients with r J Ophthlmol: first published s /bjo on 1 July Downloded from on 15 September 218 by guest. Protected by copyright.

6 iometry ofthe crystlline lens in lte onset dibetes: the importnce ofdibetic type Tble5 Slope estimtes(±95% C)forthe effect ofdibeticdurtion (mmlyer) on biometryin erly onset dibetics cross the ge qurtiles fter ccountingfor the (norml) effect ofge Durtion estimte (95% C) ge qurtile Lens Cortex Nucleus C FR K 1st -2* -19* * t --45* (-11) (-1) ( 54) (-13) (-55) (-28) 2nd -19t -16* t t - 3* (-7) (-7) ( 34) ( 8) (-33) (-17) 3rd -16t -13t -29* --16t --84t --16* ( 5) (-5) (-25) ( 6) (-25) (-13) 4th -18t -14t -38* -.11* --56* --13 ( 6) ( 6) (-26) (-7) (-29) (-17) 95% C=95% confidence intervl; C=nterior chmber depth; FR=front rdius of curvture of lens; K=bck rdius ofcurvture of lens; ge qurtiles: lst= 1 to <26; 2nd=26 to <42; 3rd=42 to <58; 4th= 58 to 74 yers; *=p<.5; t=p< 16; confidence intervls nd p vlues clculted by the intrclss correltion model of Rosner.2324 Tble 6 ffect ofdibetic durtion on lens biomteny in groups with different ge ofonset of dibetes fter ccounting for the (confounding) effects ofge nd sex ge t onset ofdibetes (number ofsubjects) Lens Cortex Nucleus C FR K to <1(43) <16* < loto<2(6) < to <3(43) -1-4 t to <4(19) NS NS -66 NS -68 NS 4 to <5(3) NS -38 NS NS NS -51 5to <6(29) NS NS NS NS NS NS 6+ (2) NS NS NS NS NS NS C=nterior chmber depth; FR=front rdius of curvture of lens; K=bck rdius of curvture of lens; *p vlues clculted by the intrclss correltion model of Rosner.2324 'worse' dibetic stte tend to be concurrently ffected by lens chnges nd retinopthy. s discussed in our previous publiction,5 disturbnce of the ctul growth of the lens (by either hyperplstic or hypertrophic mechnism or both) would be consistent with the finding in erly onset dibetes of powerful dibetic durtion effect. With the modest chnges found in lte onset dibetes, nd the bsence of ny demonstrble effect of dibetic durtion, it is necessry to question whether the mechnisms of the disturbnces to the lens re different in the two types of dibetes. The rgument in fvour of disturbnce of ctul lens growth in erly onset dibetes is prtly bsed upon the finding of powerful dibetic durtion effect in this group, nd is perhps supported indirectly by the observtion tht biometry is preferentilly disturbed in subjects with dibetic retinopthy. n the bsence of durtion effect the slightly incresed lens thickness in lte onset dibetes could be explined simply in terms of n ion/ wter imblnce with generlised (extrcellulr) lens swelling. The ide tht lenticulr swelling might increse over time (durtion) with cumultive membrne dmge in erly onset dibetes but not in lte onset dibetes seems intrinsiclly unstisfctory, nd rgues ginst 'progressive swelling' of the lens s the mechnism of disturbed biometry in erly onset dibetes. Differences between erly nd lte onset dibetics re well recognised, with prolifertive dibetic retinopthy.29 being commoner, nd end stge renl filure'434 being bout 15 times more common in Type 1 thn Type 2 dibetics. Crdiovsculr complictions on the other hnd re commoner mong Type 2 dibetics We conclude tht in the present study substntil differences in nterior oculr segment biometry hve been demonstrted between erly nd lte onset dibetics. These biometric findings 433 my reflect fundmentl pthophysiologicl differences between Type 1 nd Type 2 dibetes. The uthors re grteful to Dr D Hockdy, Dr J Mnn, Mr H Cheng, Mr P wdry, nd Mr Freedmn for llowing their ptients to be recruited to this study, nd to Dr J Thompson nd Dr J ithell for sttisticl dvice. This work ws supported by Oxford Regionl Helth uthority NHS Loclly Orgnised Reserch Grnt Number 85/19 nd by ritish Dibetic ssocition Reserch Grnt. 1 Wele R. The ging eye. London: HK Lewis, 1%3. 2 Weekers R, Delmrcelle Y, Luyckx-cus J, Collignon J. Morphologicl chnges of the lens with ge nd ctrct. n: lliot K, Fitzsimons DW, eds. The hunn lens in reltion to ctrct. C Foundtion Symposium 19, 1973; rown NP. Dting the onset of ctrct. Trns Ophthlmol Soc UK 1976; 96: Mrshll J, econsfield M, Rothery S. The ntomy nd development of the humn lens nd zonules. Trns Ophthlmol Soc UK 1982; 12: Sprrow JM, ron J, rown NP, Neil HW. iometry of the crystlline lens in erly-onset dibetes. rj Ophthlmol 199; 74: rown NP, Sprrow JM, ron J. Centrl compction in the process of lens growth s indicted by lmellr ctrct. rj Ophthlmol 1988; 72: rown NP. The chnge in lens curvture with ge. xp ye Res 1974; 19: Huggert. The ppernce of the bnd of disjunction of the lens in dibetes mellitus. ct Ophthlmol (Kbh) 1953; 31: rown NP, Hungerford J. The influence of the size of the lens in oculr disese. Trns Ophthlmol Soc UK 1982; 12: Fledelius HC, Miymoto K. Dibetic myopi - is it lensinduced? ct Ophthlmol (Kbh) 1987; 65: Sprrow JM. The lens in dibetes. D Phil Thesis, Lincre College, University of Oxford, Neil HW, Gtling W, Mther HM, Thompson V, Thorogood M, Fowler GH, et l. The Oxford community dibetes study: evidence for n increse in the prevlence of known dibetes in Gret ritin. Dibet Med 1987; 4: Dibetes mellitus. Report ofwho studygroup. WHO technicl report series 727. Genev: WHO, Jrrett JR. Dibetes mellitus. (Series in clinicl epidemiology). London, Sydney: Croom Helm, rown NP, Tripthy R. The loss of the nterior cler zone of the lens, prognostic significnce in ctrct formtion. Trns Ophthlmol Soc UK 1974; 94: Perkins S. Lens thickness in erly ctrct. rj Ophthlmol 1988; 72: Sprrow JM, ron J, rown NP, yliffe W, Hill R. The Oxford clinicl ctrct clssifiction nd grding system. nt Ophthlmol 1986; 9: Sprrow JM, yliffe W, ron J, rown NP, Hill R. nter-observer nd intr-observer vribility of the Oxford clinicl ctrct clssifiction nd grding system. nt Ophthlmol 1988; 11: rown NP. Slit-imge photogrphy. Trns Ophthlmol Soc UK 1969; 89: rown NP. n dvnced slit imge cmer. rj Ophthlmol 1972; 56: rown NP. Quntittive slit-imge photogrphy of the lens. Trns Ophthlmol Soc UK 1972; 92: Sprrow JM, rown NP, Shun-Shin G, ron J. The Oxford modulr ctrct imge nlysis system. ye 199; 4: Rosner. Sttisticl methods in ophthlmology: n djustment for the intrclss correltion between eyes. iometrics 1982; 38: Rosner. Multivrite methods in ophthlmology with pplictions to other pired dt situtions. iometrics 1984; 4: Cohen J. Sttisticl power nlysis for the behviorl sciences. Chpter 9, 2nd ed. London: Lwrence rlbum, Green, Hughe M, Holm NN, Rsch LL. pidemiologicl studies of dibetes mellitus in Denmrk.. prevlence study bsed on insulin prescriptions. Dibetologic 1981; 2: orch-johnson K, Kreiner S, Deckert T. Mortlity of Type 1 (insulin-dependent) dibetes in Denmrk. Dibetologic 1986; 29: gner T, Dnem P, inder C. Remission in insulin-dependent dibetes mellitus: prospective study of bsl C-peptide nd insulin dose in 286 consecutive ptients. Dibetes Cre 1987; 1: Klein R, Klein K. Vision disorders in dibetes. n: Dibetes in meric. Chpter X. US Deprtment of Helth & Humn Sciences, NH Publiction no , Hermn WH, Teutsch SM. Kidney disese ssocited with dibetes mellitus. n: Dibetes in meric. Chpter XV. US Deprtment of Helth & Humn Sciences, NH Publiction no , Pyorl K, Lkso M. Mcrovsculr disese in dibetes mellitus. n: Mnn J, Pyorl K, Teuscher, eds. Dibetes in epidemiologicl perspective. dinburgh: Churchill Livingstone, 1983; r J Ophthlmol: first published s /bjo on 1 July Downloded from on 15 September 218 by guest. Protected by copyright.