Current management of Diabetic Maculopathy

By Oluleye TS Senior Lecturer, consultant vitreo retinal surgeon, retinal Unit, dept of ophthalmology, UCH Ibadan !aper presented at OS", #bu$a, September %&'&

Introduction (iabetic )ellitus is no* considered a pandemic disease The +orld Health Organi,ation reported that about '-. million people *orld*ide suffer from diabetes and that about t*o third of them are in the developing countries ' By the year %&/&, the number of people living *ith the disease *ill be more than double % In the past, diabetes *as thought to be foreign, but no*, there is a global trend to*ards increase of the incidence and prevalence of diabetes in #fricans / (iabetic retinopathy is a ma$or cause of blindness in the developed *orld Ho*ever, the changing lifestyle of people in developing countries is bringing this disease to the fore (iabetic retinopathy is no* a significant cause of blindness in developing countries such as India, 0 and "igeria.,1 Diabetic Maculopathy )a$ority of diabetic maculopathy occur in "on Insulin (ependent (iabetes )ellitus 2"I(()3, 4 )acular ischemia is more fre5uent in Insulin (ependent (iabetes )ellitus 2I(()3, 6 after %& years of 7no*n diabetes, the prevalence of diabetic macular edema 2()83 is appro9imately %6: in both type ' and type % diabetes (iabetic maculopathy consist of non; clinically significant macular edema, clinically significant macular edema < focal or diffuse 2spongiform, foveal detachment and vitreo macular traction3=, cystoid macular edema and ischemic maculopathy (iabetic )acular edema 2()83 is the leading cause of moderate

visual loss in people *ith diabetes >isual loss from ()8 is five times more than that from proliferative diabetic retinopathy 2!(?34 Pathophysiology of diabetic macular edema 10 The pathophysiology of diabetic macular edema is e9plained by micro angiopathies that occur in diabetics This includes retinal microvascular change, thic7ening of retinal capillary basement membranes and reduction in the number of pericytes There is loss of autoregulation, increased permeability, incompetence of retinal vasculature and edema The above mechanisms produce impaired o9ygen diffusion, *hich stimulate the production of vascular endothelial gro*th factor 2>8@A3
''

>8@A may

induce retinal vascular permeability through phosphorylation of the tight $unctional protein occludin, resulting in the dissolution of the $unctional comple9 '% Other pathogenetic mechanisms include endothelial cell apoptosis and retinal endothelial cell intercellular adhesion molecule;' and C( '6 induced Inflammation #ll the above mechanisms results in retinal vascular permeability and compromise of blood;retinal barrier leading to lea7age of fluid and plasma constituents in the surrounding retina

Aigure' Clinically significant macular edema 2Hard e9udates and edema *ithin .&&microns to center of fovea3

Aigure % Hard e9udates and diffuse macular edema, fundus flourescein angiography sho*ing diffuse lea7age and cystoids macular edema

Aigure / Cystoid macular edema, fundus flourescein angiography sho*ing cystoid changes

Macular Ischemia )acular ischemia is a devastating condition that causes irreversible visual loss It occur more in type I diabetes'/ !athogenesis of macular Ischemia include basement membrane thic7ening, increased viscosity of blood and endothelial cell damage This result in closure of perifoveal capillaries as evidenced by irregular *idening of fovea avascular ,one 2A#B3 and budding of capillaries into A#B on fundus flourescein angiography2 AA#3

Aigure 0 )acular ischemia 2 note occluded vessel, arro* 3, AA# sho*ing enlarged fovea avascular ,one arro*, and capillary non perfused areas, blue arro* Diagnosis of diabetic maculopathy Clinical e9amination of the retina *ith the slit lamp biomicroscopy using the 46 or -& diopter non contact fundus lens *ill sho* retinal elevation and s*elling This method of e9amination offer stereoscopic and magnified vie* of the retina Aundus flourescein angiography *ill sho* lea7age and capillary non

perfused areas and is indicated in diabetics *ith une9plained visual loss to rule out macular ischemia Optical coherence tomography is a non invasive diagnostic tool used to 5uantify macula edema It is also useful in patient education and monitoring follo* up response to treatment Treatment of diabetic Maculopathy The standard of treatment for diabetic macular edema should include glycemic control and optimal blood pressure control as demonstrated by the (iabetes Control and Complications Trial 2(CCT3 and the United Cingdom !rospective (iabetes Study 2UC!(S3 '0,'. #nemia and nephropathy should also be controlled

Laser photocoagulation The 8arly Treatment (iabetic ?etinopathy Study 28T(?S3 set the guidelines for the treatment of diabetic macular edema The study found that laser reduced the ris7 of moderate visual loss from diabetic macular edema by .&: '1

Aigure . Aocal laser2 blac7 spots3 around microaneurysms 2red dots3D @rid laser along a ECF pattern sparing the A#B2 fovea avascular ,one3 and the papillo; macular bundle Laser spot of '&&microns, !o*er of '&&)*, and at duration of '&&ms is recommended The slit lamp delivery method *ith a macular contact lens is preferred The laser spots are placed as sho*n in figure . The fovea avascular ,one is spared Complications of laser treatment include transient retina edema, accidental foveolar burns, paracentral scotomas, laser scar e9pansion, subretinal fibrosis and choroidal ne* vessles The complications associated *ith laser treatment can be devastating hence the need for alternative therapy Aor microaneurisms and macular edema affecting the center of fovea, laser treatment is not

suitable

Corticosteroids such as Triamcinolone has been given intravitreally 2at a dose of 0mg in

& 'mls3, and via the posterior subtenon route2 at a dose of %&mg3 *ith success '4 ?ecently slo* release steroids such as fluocinolone acetonide has been implanted into the vitreous cavity *ith reduction in the macular edema and improvement in vision '6 Complications of steroids such as cataract and raised intraocular pressure have limited their use The (iabetic Clinical ?esearch "et*or7 2(C?"et3 in a randomised trial found that laser *as superior to triamcinolone in the treatment of diabetic macular edema on the long term '- In Gune %&'&, (C?"et compared the anti >8@A ranibi,umab *ith laser and triamcinolone in a randomised trial and found ranibi,umab2 at a dose of & /mg3 to be superior to both laser and triamcinolone either alone or in combination *ith laser %& Bevaci,umab2 at a dose of

' %.mg3 , an anti>8@A similar to ranibi,umab has also been found to be superior to laser in The BOLT study, another randomised trial%' In developing nations li7e "igeria, bevaci,umab is preferred to ranibi,umab, in vie* of the prohibitive cost of the latter Ho*ever, the former is used as an off label drug The recent C#TT trial 2 Comparism of Age related maculopathy Treatment Trial3 has demonstrated that both medications have e5ual efficacy %% It is important to note that the anti>8@A in$ections *ere given monthly ?is7s such as endophthalmitis should be borne in mind )acular edema *ith vitreomacular traction has been sho*n by the (C?"et to benefit from vitrectomy%/ The treatment of macular ischemia has been disappointing #nti>8@A and laser treatments are contraindicated %0, %. Conclusion (iabetic maculopathy is an important cause of visual loss in diabetics Therefore all ne*ly diagnosed diabetics should have dilated fundoscopy *ith 46 or -&( e9amination of their macula #ll diabetic

patients *ith une9plained visual loss should have flourescein angiography to rule out macular ischemia 8arly recognition and prompt management of macular edema *ill prevent irreversible visual loss

R ! R "C # 1. The !revalence of (iabetic ?etinopathy #mong #dults in the United States $

The 8ye (isease !revalence ?esearch @roup #rch Ophthalmol. %&&0D'%%H..%;.1/ % +orld (iabetes AoundationH #nnual ?evie* %&&% #ccessed from *** *orld diabetes foundation org / Cing H, #ubert ?8, Herman +H @lobal burden of diabetes, '--.;%&%.H prevalence, numerical estimates, and pro$ections Diabetes Care, '--6, %'H '0'0;'0/' 0 (andona L, (andona ?, "aduvilath T G et al !opulation based assessment of diabetic retinopathy in an urban population in southern India Br J Ophthalmol '---D 6/263H-/4;0& . 1 4 6 "*osu S"" (iabetic ?etinopathy in "ne*i, "igeria Nig. J. Ophthamol "*osu S"" Lo* vision in "igerians *ith diabetes mellitus Doc. .';.4 (asT, ?ani # (iabetic 8ye (iseases "e* (elhi, Gaypee %&&1D .0;.. (as T, Galali S, >edantam >, )a$$i #B ?etinal vascular disorders Clinical !ractice of Ophthalmology "e* (elhi, G! Brothers %&&/D /.& Clein ?, Clein B8, )oss S8, et al The +isconsin 8pidemiologic Study of (iabetic ?etinopathy I> (iabetic macular edema Ophthalmology '-60D-'H'010I40 '& @raefes #rch Clin 89p Ophthamol,2 %&&63 %01H '%&/ '' #iello L!, #very ?L, #rrigg !@, et al " 8ngl G )ed (ec ' '--0D//'2%%3H'06&;4 '% #ntonetti (#, Barber #G, Chin S, et al (iabetes '--6D04H'-./I'/ (as T, Galali S, >edantam >, )a$$i #B ?etinal vascular disorders Clinical !ractice of Ophthalmology "e* (elhi, G! Brothers %&&/D /.& %&&&D62'3 H 4;'&

Ophthalmol.%&&&D'&'2'3 H

'0 (iabetes Control and Complications Trial ?esearch @roup " 8ngl G )ed /%-H-44I-61, '--/ '. UC !rospective (iabetes Study @roupH 2UC!(S /63 B)G /'4H4&/I4'/, '--6 '1 8arly Treatment (iabetic ?etinopathy Study ?eport "umber % 8arly Treatment (iabetic ?etinopathy Study ?esearch @roup Ophthalmology Gul '-64D-0243H41';40 '4 Gonas GB, #77oyun I, Creissig I, et al (iffuse diabetic macular edema treated by intravitreal triamcinolone acetonide Br G Ophthalmol %&&.D 6-H /%';1 '6 Sustained Ocular (elivery of Aluocinolone #cetonide by an Intravitreal Insert Ophthalmology ''4243 '/-/;'/-- e/ 2Guly %&'&3 '- (iabetic ?etinopathy Clinical ?esearch "et*or7 Ophthalmology %&&6D''.H'004I.%& (iabetic ?etinopathy Clinical ?esearch "et*or7 Ophthalmology %&'&D''4213H '&10;'&44 %' # !rospective ?andomi,ed Trial of Intravitreal Bevaci,umab or Laser Therapy in the )anagement of (iabetic )acular 8dema 2BOLT Study3H '%;)onth (ataH ?eport % Ophthalmology Gune %&'&, ''4213 '&46;'&61 e% %% C#TT ?esearch @roup, )artin (A, )aguire )@, Jing @S, @run*ald G8, Aine SL, Gaffe @G ?anibi,umab and bevaci,umab for neovascular age;related macular degeneration " 8ngl G )ed %&'' )ay '-D/102%&3H'6-4;-&6 8pub %&'' #pr %6 %/ (iabetic ?etinopathy Clinical ?esearch "et*or7 .>itrectomy for (iabetic )acular 8dema and >itreo macular Traction Ophthalmology %&'&D''4H'&64;'&-/ 24. Chung 8, ?oh ), C*on, O +oong C, Hyoung G 8ffects of )acular Ischemia on the Outcome of Intravitreal Bevaci,umab Therapy for (iabetic )acular 8dema ?etina %&&6D%6243H-.4;1/ %. ?ichardson 8, !atel G Hy7in @ ?educed visual acuity follo*ing standard 8T(?S macular laser for clinically significant 8ye %&&/D '4H 0/'I0//