Retinopati Diabetika

Abstrak Retinopati diabetika merupakan suatu gangguan pada mata yang disebabkan akibat penyakit diabetes mellitus yang diderita dalam waktu yang relatif lama . Jumlah insidens penderitanya yang cukup tinggi ditambah pula dengan manifestasi klinis tahap akhir berupa kebutaan ; keduanya merupakan tantangan tersendiri bagi para klinisi untuk mengoptimalkan penatalaksanaan bagi penderita diabetes mellitus sebelum mereka kehilangan daya penglihatannya . Terapi yang dilakukan hingga saat ini adalah mengontrol faktor penyebab dan laser terapi . Diperlukan telaah yang lebih dalam , agar dapat ditemukan suatu cara yang lebih optimal guna menghindari terjadinya retinopati diabetika ini pada penderita deabetes mellitus . Kata kunci : retinopati diabetika – diabetes mellitus – neuro oftalmologi Abstract Diabetic retinopathy is visual disorder cause by hiperglycemi and depend by time . Incidens for diabetic retinopathy is high, and its end stage clinical manifestation ( blind ) made this situation must become a caution for clinician to find the optimize way to prevent . So far, how to manage hiperglycemi and laser therapy are the best way that we could done . We need more courage and curious to find the better way to prevent hyperglycemi cause diabetic retinopathy . Keywords : diabetic retinopathy – diabetes mellitus – neuro ophthalmology Pendahuluan Diabetes mellitus merupakan gangguan dari metabolisme karbohidrat , dimana tepung dan gula tidak disimpan atau dipakai dengan semestinya . Hal ini menimbulkan gangguan pula pada nutrisi jaringan diseluruh tubuh, termasuk mata . Pengobatannya dengan diit dan insulin , dapat memperpanjang umur penderita diabetes mellitus , sehingga proses degenerasi dimata menjadi bertambah penting . Yang paling khas adalah penyulitnya di retina . (1,2) Retinopati diabetika biasanya timbul setelah penderita menderita diabetes mellitus selama 5 – 15 tahun. Dimana angka kejadian pada wanita lebih banyak daripada pria . Umur yang terbanyak menderita retinopati diabetika adalah 50 – 65 tahun .(3) Walaupun demikian Watkins memberikan batasan rentang umur yang lebih panjang lagi yaitu berkisar antara 30 – 69 tahun .(9) Retinopati ini merupakan penyulit yang paling penting dari diabetes mellitus , dengan frekuensi 40 – 50% dari penderita diabetes . Prognosanya kurang baik untuk penglihatan. Di Amerika Serikat , 5000 orang

pertahunnya menjadi buta oleh retinopati diabetika, sedang di Inggris , keadaan ini merupakan penyebab kebutaan nomor 4 dari seluruh penyebab kebutaan . Selain oleh karena kelainan endokrin, stresspun dapat menimbulkan diabetes mellitus .(3) Patogenesa Beberapa teori dikatakan dapat menyebabkan terjadinya retinopati diabetika . Namun terdapat 2 buah teori yang paling banyak menarik perhatian para pakar , yaitu (10) 1. Teori Enzim katalisis aldose reduktase . Enzim ini akan mengkatalisa perubahan glukosa menjadi sorbitol . Bila kadar glukosa intraselular meningkat , hal ini akan meningkatkan pula kadar sorbitor intraselular, yang kemudian akan menghambat sintesis mio-inositol yang terdapat pada glomerular dan jaringan saraf . Penurunan kadar mio-inositol ini akan menurunkan metabolisme fosfo-inositidin, yang kemudian akan menurunkan aktivitas dari Na-K-ATPase dan memperburuk kerusakan mikrovaskular .

2. Teori protein Aminoguanidin . Aminoguanidin ( suatu fraksi dari protein esensial ) , melalui mekanisme yang masih terus diselidiki , pada tikus tikus percobaan ternyata dapat memperlambat pertambahan mikroaneurisma kapiler di retina . Retinopati diabetika merupakan mikroangiopati , sebagai akibat dari gangguan metabolik , yaitu defisiensi insulin dan hiperglikemi . Peningkatan gula darah sampai ketinggian tertentu , mengakibatkan keracunan sel sel tubuh , terutama darah dan dinding pembuluh darah , yang disebut glikotoksisitas. Peristiwa ini merupakan penggabungan irreversibel dari molekul glukosa dengan protein yang disebut proses glikosilase protein .
(1,2,3)

dan penumpukan deposit protein pada kapiler

Dalam keadaan normal , proses glikosilase ini hanya sekitar 4-9% , sedang pada penderita diabetes mencapai 20% .(4) Glikosilase ini dapat mengenai isi dan dinding pembuluh darah , yang secara keseluruhan dapat menyebabkan meningkatnya viskositas darah , gangguan aliran darah , yang dimulai pada aliran didaerah sirkulasi kecil ,

kemudian disusul dengan gangguan pada daerah sirkulasi besar dan menyebabkan hipoksia jaringan yang diurusnya . Kelainan kelainan ini didapatkan juga didalam pembuluh pembuluh darah retina , yang dapat diamati dengan melakukan (2) 1. fundus fluorescein angiography 2. pemotretan dengan menggunakan film berwarna 3. oftalmoskop langsung dan tak langsung 4. biomikroskop dengan lensa kontak dari goldman Mula mula didapatkan kelainan pada kapiler vena, yang dindingnya menebal dan mempunyai affinitas yang besar terhadap fluoresein . Keadaan ini menetap untuk waktu yang lama tanpa mengganggu penglihatan . Dengan melemahnya dinding kapiler , maka akan menonjol membentuk mikroaneurisma . Mula mula keadaan ini terlihat pada daerah kapiler vena sekitar makula, yang tampak sebagai titik titik merah pada oftalmoskop . Adanya 1-2 mikroaneurisma sudah cukup mendiagnosa adanya retinopati diabetika .(2) Pada keadaan lanjut , mikroaneurisma didapatkan sama banyaknya pada kapiler vena maupun arteri . Baik kapiler yang abnormal maupun aneurisma menibulkan kebocoran , yang tampak sebagai edema, eksudat, perdarahan, di sekitar kapiler dan mikroaneurisma .
(8)

Adanya edema dapat mengancam ketajaman penglihatan bila terdapat di daerah makula, edema yang ringan dapat diabsorbsi, tetapi yang hebat dan berlangsung dalam waktu relatif lama akan menyebabkan degenerasi kistoid . Bila hal ini terjadi di daerah makula , ketajaman penglihatan yang terganggu, tak dapat dikembalikan kepada keadaan semula meskipun dilakukan fotokoagulasi pada pengobatan . (4,5) Perdarahan selain akibat kebocoran juga dapat disebabkan oleh karena pecahnya mikroaneurisma . Kebocoran lipoprotein , tampak sebagai eksudat keras , menyerupai lilin berkelompok yang berbentuk lingkaran di daerah makula, yang disebut bentuk sirsiner berwarna putih kekuning kuningan . Eksudat lemak ini didapatkan pada penderita yang gemuk dengan kadar lemak darah yang tinggi . (2,3 ) Akibat perubahan isi dan dinding pembuluh darah , dapat menimbulkan penyumbatan yang dimulai di kapiler, kearteriola, dan pembuluh darah besar ; karenanya timbul hipoksi, disusul dengan daerah iskemik kecil dan timbulnya kolateral kolateral . Hipoksi mempercepat timbulnya kebocoran, neovaskularisasi, dan mikroaneurisma yang

tetapi bila sudah terjadi pembentukan jaringan fibrovaskuler . Edema. yang merupakan bercak nekrose . Perdarahan yang timbul didalam badan kaca dapat menyebabkan glaukoma hemoragik . Letaknya intraretina dan menjalar menjadi preretina . perdarahan yang terdapat di daerah makula.(7) Timbulnya gangguan visus.(7. Neovaskularisasi ini diikuti kemudian diikuti dengan jaringan proliferasi . sehingga didapatkan perdarahan sepanjang pembuluh darah vena .8) Pembuluh darah vena melebar dengan lumen dan diameter yang tidak teratur. Gangguan aliran darah vena juga merangsang timbulnya pembuluh darah baru yang dapat timbul dari pembuluh darah yang ada di papil atau dimana saja . karena pecahnya rubeosis iris . (2) Neovaskularisasi juga timbul pada permukaan iris yang disebut rubeosis iris. Hal ini dapat menimbulkan penurunan ketajaman penglihatan sampai kebutaan . Manifestasi klinis Penurunan ketajaman pada penglihatan sentral berlangsung secara perlahan lahan . pada masa sebelum dibentuk jaringan fibrovaskuler.(9) Kelainan kelainan yang didapat pada retinopati diabetika : (2) (8) . Juga disini terjadi kebocoran dan penyumbatan. yang disebut makulopati. gangguan visus pasti menyusul . tergantung dari besar dan lokasi kelainan.(7) Perdarahan di dalam badan kaca juga diikuti dengan pembentukan jaringan fibrotik yang disertai neovaskularisasi . yang dapat menimbulkan glaukoma akibat tertutupnya sudut bilik mata oleh pembuluh darah baru tersebut dan juga akibat perdarahan . Bentuknya dapat berupa gulungan atau rete mirabile . cepat menimbulkan gangguan penglihatan. Akibat hipoksi timbul eksudat lunat yang disebut cotton wool patch . luas dan beratnya kelainan . bila tidak diambil tindakan . yang sangat sakit dan menimbulkan kebutaan . retinopati diabetika cepat atau lambat akan berakhir dengan kebutaan . yang juga dapat mengkerut dan menyebabkan ablasi retina dan kebutaan .baru . eksudat. Dengan demikian. Pada umumnya visus pada stadium ini masih baik. tergantung dari lokalisasi.(5) Bila jaringan fibrivaskular ini mengkerut dapat menimbulkan perdarahan dan tarikan pada retina sehingga menyebabkan ablasi retina dengan atau tanpa robekan .

Mula mula terdapat pada retina. akibat pengurangan aliran darah arteri karena obstruksi kapiler 5.000 kasus baru . Shunt arteri vena . yang merupakan tanda khas. Pelebaran vena . b. terjadi akibat kelainan sirkulasi . Pada angiografi fluoresin tampak sebagai kebocoran fluoresin diluar pembuluh darah . 9. Akibat proliferasi sel sel endotel . 6. Bila neovaskularisasi ini pecah dapat menimbulkan perdarahan di retina. akibat gangguan permeabilitas mikroaneurisma atau karena pecahnya kapiler . hard eksudat : berwarna kuning karena eksudasi plasma yang lama . berupa tonjolan dinding kapiler. tampak sebagai pembuluh darah yang berkelok kelok . tampak sebagai perdarahan bulat kecil didaerah papil dan makula . Obstruksi kapiler . kondisi ini merupakan penyebab utama dari gangguan penglihatan pada pasien pasien diabetes . Terutama terdiri dari lipid yang didapatkan pada hiperlipoproteinemia . Edema makula .1. kemudian menjalar ke preretina untuk kemudian masuk kedalam badan kaca. Berdasarkan kelainan diatas . dan juga didalam badan kaca . Neovaskularisasi preretina diikuti pula dengan proliferasi sel glia . timbul neovaskularisasi . tidak berbatas tegas. 7. cotton wool patch : berwarna putih . 8. lumennya tidak teratur. preretina. dihubungkan dengan iskemik retina . Eksudat berupa : a. Mikroaneurisma. Perdarahan bintik atau perdarahan bercak. dengan vena sedikit melebar dan . 2. Dapat disertai kelainan endotel dan eksudasi plasma . berkelok kelok. didapatkan 75. Mikroaneurisma . Dalam setahunnya di Amerika . yang merupakan tanda awal dari penyakit yang berat . 4. Merupakan tanda awal dari retinopati diabetika 3. yang menyebabkan berkurangnya aliran darah dalam kapiler retina. Daniel Vaughan membagi retinopati diabetes menjadi stadium : (2) I.

Stadium II + cotton wool patches.(6) Fotokoagulasi dengan Xenon Arc Fotokoagulator atau Argon Laserphoto Koagulator . Tujuan dari fotokoagulasi ini adalah menutup . dan terletak dilapisan pleksiform luar . tersebar . Kontrol gula yang ketat dapat menurunkan insidens dan perbutukan dari retinopati diabetika ini . arteriosklerosis dan hipertensi arteri 2. Derajat retinopati ini berhubungan erat dengan lamanya diabetes melitus diderita .(5) Diabetes pada orang muda . sebagai akibar iskemik pada arteriola terminal . Terapi Pengobatan dari diabetes melitusnya sendiri dengan diit dan pemberian obat obat anti diabetik . Pengobatan yang baik dapat memperlambat timbulnya retinopati . tampaknya tidak ada satu obatpun yang mampu mempengaruhi jalannya keadaan ini . dapat menyebabkan retinopati diabetes yang hebat dalam 20 tahun meskipun dikontrol dengan baik . II. terutama pada penderita diabetes IDDM . sianosis. Vena melebar . IV. Disusul dengan terjadinya retinitis proliferans . yang diakibarkan timbulnya jaringan fibrotik dan neovaskularisasi . Perdarahan besar di retina dan preretina. disertai sheating pembuluh darah .(7) Beberapa keadaan yang dapat memperberat retinopati diabetes adalah (2. sehingga mengurangi kebutuhan metabolisme dan berakibat regresinya neovaskularisasi . III.secara histologis didapatkan mikroaneurisma di kapiler bagian vena dilapisan nuklear luar . hipoglikemi 3. V. Vena vena melebar. terdapat pada semua lapisan retina dan preretina . tampak eksudat kecil kecil seperti lilin . Perdarahan nyata besar dan kecil.3) 1. kehamilan pada penderita diabetes juvenilis. Dimana sinar dari alat tersebut ditembakan secara tidak langsung sehingga menimbulkan jaringan parut di khorioretina. juga infiltrasi ke badan kaca . namun sekali timbul . hiperlipoproteinemi 4.

dan sangat berpotensi menyebabkan kecacatan Daftar Pustaka 1. Ocular Problem in Diabetes Mellitus . Prevention and treatment of the complication of Diabetes Mellitus. BMJ April 2002.com/fsumantri/retinopatidiabetika.htm .Clark CM.326:924-926 10. Clinical Evidence of Retinopathy Diabetic : Virectomy in people with maculopathy . ABC of diabetes retinopathy .327:1060-1061 7. mencegah timbulnya ablasi retina .(7) Kesimpulan : 1. Ryder B . Sudiana N . Kohner EM .333(12): 810 http://www. E medicine 2004 4. Ilmu Penyakit Mata.Aspirin for diabetic retinopathy . baik yang setuju ataupun tidak . Valero SO. BMJ 2003. . akan memperlambat perjalanan retinopati diabetika Terapi yang digunakan hingga saat ini adalah kontrol yang ketat dari diabetes melitus dan fotokoagulasi . Feman SS . Kohner E. NEJM July 329: 286-287 9. Christie B . Harding S.kebocoran . Perjalanan penyakit akan semakin memberat bila faktor penyebabnya yaitu diabetes melitus tidak diatasi . 5. Slack Incorporated New Jersey 2001. Neuro-ophthalmology Review Mannual 5th ed. mengurangi neovaskularisasi.freewebs. Kline LB. Penatalaksaan diabetes yang tepat . Retinopati diabetika merupakan salah satu penyulit yang paling penting pada penderita diabetes melitus berupa kebutaan . 3. Pembetian aspirin pada keadaan retinopati diabetika hingga saat ini masih mengundang berbagai pendapat . Watkins PJ . 155-6 2. Lee DA . Background of retinopathy Diabetic . NEJM 1995. dengan harapan dapat menghambat menurunnya visus. NEJM April BMJ 2003. E-medicine 2005 5. Scotland to start screening programme for diabetic retinopathy. merangsang penyerapan cairan . Bajandas FJ . 3. Trisakti Press . BMJ 1995.311:207-208 6. Screening for diabetic retinopathy . Droilhet JH . 2. 4.324:871 8. Jakarta 1990.

lapisan pembuluh dibelakang mata yang mendeteksi cahaya dan membantu mengirimkan gambar ke otak. . adalah tahap awal dari retinopati diabetika. Dalam tahap ini. Banyak orang dengan diabetes memiliki NPDR ringan. Kerusakan pada pembuluh darah di retina disebut sebagai retinopati diabetika. yang biasanya tidak mempengaruhi penglihatan mereka. Cairan tersebut menyebabkan kebengkakan pada retina atau menyebabkan penyumbatan yang disebut exudates. area kecil di tengah retina yang membuat kita melihat secara lebih detil. akan tetapi dalam kasus terburuk penglihatan periperal masih dapat berfungsi. pembuluh darah kecil di dalam retina mengalami kebocoran darah atau cairan. tubuh anda tidak dapat menggunakan dan menyimpan gula dengan benar. Hilangnya penglihatan bisa ringan atau parah. Edema macular adalah pembengkakan atau penebalan pada macula. Pembengkakan disebabkan oleh kebocoran cairan pada pembuluh darah retina. Ini adalah penyebab yang paling umum berkurangnya penglihatan karena diabetes. Ketika penglihatan terpengaruh itu adalah hasil dari edema macular. Jika anda memiliki diabetes mellitus. Level gula darah yang tinggi dapat merusak pembuluh darah di retina.Diabetes dapat mempengaruhi penglihatan. Mata Normal Jenis-jenis Retinopati Diabetika Terdapat 2 jenis diabetic retinopathy: Nonprofile(NPDR) dan PDR Mata dengan Retinopati Diabetika NPDR dikenal sebagai retinopathy latar belakang.

Retinopati diabetika Proliferatif dapat menyebabkan penglihatan dengan berbagai cara seperti berikut : hilangnya Vitreous Hemorrhage : Pembuluh darah baru yang rapuh dapat mengalami kebocoran sehingga darah masuk ke dalam vitreous. Kehilangan penglihatan yang parah dapat terjadi bila macula atau bagian besar retina terlepas. bulanan atau bahkan tahunan untuk dapat menyerap kembali darah yang berada pada vitreous. Traction Retinal Detachment : Ketika PDR muncul. mengkerut dan menarik retina dari posisi normal. Vitreous Hemmorhage sendiri tidak dapat menyebabkan hilangnya penglihatan secara permanen. Jika Vitreous Hemmorhage besar maka dapat menutupi seluruh penglihatan. Jika mata tidak dapat membersihkan darah tersebut pada waktunya. Glaukoma Neovaskular : terkadang. Penyebab utama dari PDR adalah banyaknya pembuluh darah retina yang tertutup sehingga aliran darah menjadi tidak lancar. Hal tersebut membutuhkan waktu harian. Penglihatan menjadi rabun dikarenakan macula tidak mendapat asupan darah yang cukup untuk bekerja dengan sempurna. PDR muncul ketika pembuluh darah baru yang abnormal (neovascularization) mulai tumbuh pada permukaan retina atau saraf optik. penutupan yang berlebihan pada pembuluh darah retina dapat menyebabkan munculnya pembuluh darah abnormal baru pada iris (bagian berwarna pada mata) dan menghalangi keluarnya cairan dari mata. Retina merespon dengan menumbuhkan pembuluh darah baru dengan maksud untuk menyuplai darah pada area dimana pembuluh darah asli tidak mampu lagi untuk berfungsi. jika vitreous hemmorhage yang terjadi tidak besar maka seseorang dapat melihat beberapa floater hitam pada pandangannya. maka operasi vitrectomy harus dilakukan. tergantung dari banyaknya darah yang ada. . Pengerutan macula dapat menyebabkan distorsi visual. zat seperti gel bening yang mengisi pusat mata.Iscemia macula terjadi apabila pembuluh darah kecil (kapiler) menutup. jaringan bekas luka yang berhubungan dengan neovascularization dapat mengecil. Ketika sudah tidak ada darah yang menutupi maka penglihatan akan kembali seperti sebelumnya kecuali bila macula telah rusak.

laser difokuskan pada semua bagian retina kecuali pada macula. BAGAIMANA MENDIAGNOSA RETINOPATI DIABETIKA? Pemeriksaan pada mata adalah satu-satunya cara untuk mendeteksi adanya perubahan di dalam mata. Tujuan utama dari perawatan adalah untuk mencegah bertambah hilangnya penglihatan.Tekanan pada mata akan meningkat. Sangat jarang bagi orang2 yang memiliki penglihatan rabun akibat edema macula untuk memperoleh kembali penglihatan normal mereka. Untuk PDR. Dokter mata memeriksa pupil anda dengan optalmoskop. Jika dokter mata menemukan adanya retinopati diabetika maka dokter tersebut akan memfoto mata anda atau dengan tes khusus yang disebut fluoresen. PDR dan neovaskular glaucoma. Perawatan panrentinal photocoagulation membuat pembuluh darah baru yang abnormal untuk mengecil dan mencegahnya untuk tumbuh di masa depan. laser difokuskan pada retina yang rusak dekat dengan macula untuk mengurangi kebocoran cairan. Titik tersebut biasanya akan memudar seiring waktu tetapi tidak hilang sama sekali. Kontrol gula darah yang teratur dapat mengurangi resiko jangka panjang dari hilangnya penglihatan oleh diabetes. Jika terdapat tekanan darah tinggi dan masalah ginjal harus segera dilakukan perawatan. Dokter mata seringkali dapat mendiagnosa dan menangani penyakit pada retina bahkan sebelum anda menyadari penglihatan anda bermasalah. Untuk edema macula. meskipun beberapa orang mengatakan mengalami pengingkatan parsial. . Operasi Laser : Operasi laser seringkali disarankan untuk pada penderita yang memiliki masalah macula edema. penyakit mata yang berbahaya yang dapat menyebabkan kerusakan pada optik mata. Beberapa orang mungkin melihat titik laser dekat dengan pusat peglihatan setelah perawatan. BAGAIMANA PERAWATAN RETINOPATI DIABETIKA? Penanganan terbaik dengan mencegah pertumbuhan retinopathy sebesar mungkin. menyebabkan glaucoma. Hal ini juga mengurangi kemungkinan pendarahan pada vitreous atau distorsi retina akan timbul. Dalam tes ini sejenis pewarna akan disuntikkan pada lengan anda dan mata anda akan difoto untuk mendeteksi dimana letak kebocoran.

Dokter mata boleh menyarankan untuk vitrectomy. Operasi harus dilakukan lebih awal karena distorsi macular atau lepasnya retina dapat menyebabkan hilangnya penglihatan secara permanen. Semakin lama terjadi distorsi macular semakin serius kurangnya penglihatan. yang dilakukan di dalam ruang operasi. Karena retinopathy dapat menyebar dengan cepat pada masa kehamilan. Vitrectomy : Pada PDR tingkat lanjut. Kunjungan lebih sering harus dilakukan apabila didiagnosis mengidap Retinopati Diabetika. Dokter mata akan menunggu selama beberapa bulan sampai dengan setahun untuk melihat apakah darah tersebut akan menghilang dengan sendirinya atau harus dilakukan Vitrectomy. Perubahan yang cepat pada kadar gula darah dapat menyebabkan fluktuasi penglihatan di kedua mata bahkan jika tidak terdapat Retinopati Diabetika. Wanita hamil dengan diabetes harus menjadwalkan kunjungan pada tiga bulan pertama. Jika anda ingin diperiksa untuk kacamata. Vitrectomy dapat mencegah pendarahan lanjutan dengan membuang pembuluh abnormal yang menyebabkan pendarahan tersebut. sangat penting untuk mengontrol kadar gula darah anda terlebih dahulu sebelum menemui dokter mata. dapat diperbaiki pada saat operasi Vitrectomy. KAPAN UNTUK MENJADWALKAN PEMERIKSAAN? Orang dengan diabetes harus menjadwalkan pemeriksaan setidaknya setahun sekali. Selama prosedur operasi ini. Kacamata tidak akan berfungsi dengan baik ketika gula darah kita tidak stabil. Operasi laser tidak dapat menyembuhkan Diabetic retinopathy dan tidak selalu dapat mencegah berkurangnya penglihatan. vitreous yang dipenuhi dengan darah akan dibuang dan diganti dengan larutan bening.Perawatan laser berkala terkadang dibutuhkan. Jika anda didiagnosa diabetes anda harus memeriksakan mata anda : dalam jangka waktu lima tahun dari diagnosis jika berusia 29 tahun atau kurang. • . Jika retina terlepas.

Section of Ophthalmology. Adjunct Assistant Professor. Pathophysiology The exact mechanism by which diabetes causes retinopathy remains unclear. which have considerable impact on both the patient and the society because it typically affects individuals in their most productive years. glaucoma. Clinical Assistant Professor. cataracts. Past Chair. Consulting Staff. University of Hawaii. Retina Center. Diabetes causes an array of long-term systemic complications. MD.jec-online. Phillips Eye Institute Neal H Atebara. PA. Proliferative Abdhish R Bhavsar. Department of Ophthalmology. Clinical Associate Professor. Department of Ophthalmology. Director of Clinical Research. the most common and potentially most blinding of these complications is diabetic retinopathy. Department of Surgery. It was noted that diabetic retinopathy was reversed in women who had postpartum . but several theories have been postulated to explain the typical course and history of the disease. University of Minnesota. iris neovascularization. MD.com/index. Growth hormone Growth hormone appears to play a causative role in the development and progression of diabetic retinopathy. Diabetic. FACS. 2006 • • • • • • • • • Print This Email This Overview Differential Diagnoses & Workup Treatment & Medication Follow-up Multimedia References Keywords Introduction Background Diabetes mellitus (DM) is a major medical problem throughout the world.php? option=com_content&view=article&id=126&Itemid=124 Retinopathy. MD. and neuropathies. John H Drouilhet. Department of Surgery. Division of Ophthalmology. • http://www. John A Burns School of Medicine Contributor Information and Disclosures Updated: Sep 7.dalam jangka waktu beberapa bulan dari diagnosis jika berusia 30 tahun atau lebih. Ophthalmic complications of diabetes include corneal abnormalities. However. University of Hawaii School of Medicine.

DM causes abnormal glucose metabolism as a result of decreased levels or activity of insulin. and dilation. Increased permeability of these vessels results in leakage of fluid and proteinaceous material. increased platelet aggregation. predispose to sluggish circulation. Increased levels of blood glucose are thought to have a structural and physiologic effect on retinal capillaries causing them to be both functionally and anatomically incompetent. These microaneurysms are the earliest detectable signs of DM retinopathy. galactose to dulcitol). autoregulation of retinal capillaries). Intramural pericytes of retinal capillaries seem to be particularly affected by this increased level of glucose because of its high aldose reductase content. However. which converts sugars into alcohol (eg. This leads to retinal ischemia. If the swelling and exudation would happen to involve the macula. signify increasing hypoxia and almost always are seen bordering the areas of capillary nonperfusion. a diminution in central vision may be experienced. which. such as venous beading. glucose into sorbitol. which clinically appears as retinal thickening and exudates. such as increased erythrocyte aggregation. Infarction of the nerve fiber layer leads to the formation of cotton-wool spots (CWS) with associated stasis in axoplasmic flow. loops. leading to hypoxia. More extensive retinal hypoxia triggers compensatory mechanisms within the eye to provide enough oxygen to tissues. Aldose reductase and vasoproliferative factors Fundamentally. and adhesion. endothelial damage. eventual closure of the retinal capillaries occurs. in turn. This technique has been abandoned because of numerous systemic complications and the discovery of the effectiveness of laser treatment.hemorrhagic necrosis of the pituitary gland (Sheehan syndrome). but it also may complicate cases of proliferative diabetic retinopathy (PDR). and focal capillary occlusion. it is not exclusively seen only in patients with NPDR. decreased RBC deformability. As the disease progresses. A persistent increase in blood glucose levels shunts excess glucose into the aldose reductase pathway in certain tissues. Venous caliber abnormalities. Macular edema is the most common cause of vision loss in patients with nonproliferative diabetic retinopathy (NPDR). Ruptured microaneurysms (MA) result in retinal hemorrhages either superficially (flame-shaped hemorrhages) or in deeper layers of the retina (blot and dot hemorrhages). Loss of function of pericytes results in weakness and eventual saccular outpouching of capillary walls. This led to the controversial practice of pituitary ablation to treat or prevent diabetic retinopathy in the 1950s. eventually leading to the loss of its primary function (ie. contributes to the development of diabetic retinopathy. . Platelets and blood viscosity Several hematologic abnormalities in diabetes.

However. Mortality/Morbidity Approximately 16 million Americans have diabetes. such as vascular endothelial growth factor (VEGF). New vessels break through and grow along the surface of the retina and into the scaffold of the posterior hyaloid face. Approximately 500. only one half receives appropriate eye care. This cost does not compare to the cost in terms of loss of productivity and quality of life. with 50% of them not even aware that they have it. so does the fibrous tissue formation.000 persons have clinically significant macular edema (CSME) with an annual incidence of 75. Thus. In later stages. Approximately 8. and both tractional retinal detachments and retinal tear formation with subsequent detachment. these vessels rarely cause visual compromise. Traction may cause retinal edema. By themselves. that stimulate new vessel formation. However. Frequency United States Approximately 700. The extracellular matrix is broken down first by proteases. Clinical History .Intraretinal microvascular abnormalities (IRMA) represent either new vessel growth or remodeling of preexisting vessels through endothelial cell proliferation within the retinal tissues that act as shunts through areas of nonperfusion. Of these. they are fragile and highly permeable. These new blood vessels initially are associated with a small amount of fibroglial tissue formation. it is not surprising that diabetic retinopathy is the leading cause of new blindness in persons aged 25-74 years in the United States. Further increases in retinal ischemia trigger the production of vasoproliferative factors. as the density of the neovascular frond increases. The treatment of diabetic retinopathy entails tremendous costs. and new vessels arising mainly from the retinal venules penetrate the internal limiting membrane and form capillary networks between the inner surface of the retina and the posterior hyaloid face.000 Americans have PDR with an annual incidence of 65. retinal heterotropia. Neovascularization most commonly is observed at the borders of perfused and nonperfused retina and most commonly occur along the vascular arcades and at the optic nerve head. which leads to hemorrhage into the vitreous cavity or the preretinal space.000 eyes become blind yearly because of diabetes. As the vitreous contracts. but it has been estimated that this represents only one eighth of the costs of social security payments for vision loss. These delicate vessels are disrupted easily by vitreous traction.000. the vessels may regress leaving only networks of avascular fibrous tissue adherent to both the retina and the posterior hyaloid face. it may exert tractional forces on the retina via these fibroglial connections.000.

See Retinopathy. and concave compared to rhegmatogenous retinal detachments. mobile.Presence of new vessels but not meeting the o criteria for high-risk PDR High-risk proliferative diabetic retinopathy    NVD greater than or equal to one-third to one-half disc area (DA) Any amount of NVD with vitreous or preretinal hemorrhage NVE greater than or equal to one-half DA with preretinal or vitreous hemorrhage . • Macular edema o Leading cause of visual impairment in patients with diabetes o o o Possibly due to functional damage and necrosis of retinal capillaries In cases of PDR. CSME is defined as any of the following:    • Retinal thickening located 500 µm or less from the center of the foveal avascular zone (FAZ) Hard exudates with retinal thickening 500 µm or less from the center of the FAZ Retinal thickening 1 disc area or larger in size located within 1 disc diameter of the FAZ Classification of proliferative diabetic retinopathy o Early proliferative diabetic retinopathy . Traction retinal detachments usually appear tented up. Physical These findings occur in addition to all the findings that can be seen in nonproliferative or background diabetic retinopathy. o • • Fibrovascular tissue proliferation is usually seen associated with the neovascular complex and also may appear avascular when the vessels have already regressed. As the blood pools within this space. edema also may be caused by retinal traction if the retina is sufficiently elevated away from the retinal pigment epithelium (RPE). they may appear boat shaped. Background. patients may experience floaters. Hemorrhage into the vitreous may appear as a diffuse haze or as clumps of blood clots within the gel. patients are generally asymptomatic. which are bullous. • Neovascularization o Hallmark of PDR o • Most often occurs near the optic disc (neovascularization of the disc [NVD]) or within 3 disc diameters of the major retinal vessels (neovascularization elsewhere [NVE]) Preretinal or vitreous hemorrhage o Preretinal hemorrhages appear as pockets of blood within the potential space between the retina and the posterior hyaloid face. a combination of both mechanisms is not an uncommon finding.In the initial stages. immobile. Diabetic. blurred vision. and convex. however. However. in the advanced stages of the disease. or progressive visual acuity loss.

com/article/1225210-overview Treatment Medical Care • Glucose control: The DCCT has found that intensive glucose control in patients with insulindependent diabetes mellitus (IDDM) has decreased the incidence and progression of diabetic retinopathy. but those who have had prior panretinal photocoagulation (PRP) remain stable throughout their pregnancy. rising steadily thereafter. Although no similar clinical trials for patients with non–insulin-dependent diabetes mellitus (NIDDM) exist. 23% have NPDR after 11-13 years. Of patients with type II diabetes. in the setting of diabetic nephropathy. the American Diabetes Association (ADA) has suggested that all diabetics (NIDDM and . 25-50% of patients show some signs of retinopathy. and 60% have NPDR after 16 years. correlates well with the presence of retinopathy. Evidence suggests that aggressive treatment of the nephropathy may have a beneficial effect on the progression of diabetic retinopathy and neovascular glaucoma. Pregnant women without any diabetic retinopathy run a 10% risk of developing NPDR during their pregnancy. Those with proliferative retinopathy do poorly without treatment.Causes Risk factors • Duration of the diabetes o In patients with type I diabetes. In patients with type II diabetes. o • Renal disease. This prevalence increases to 75-95% after 15 years and approaches 100% after 30 years of diabetes. This is probably because of the fact that both conditions are caused by DM-related microangiopathies such that the presence and severity of one reflects that of the other. In fact. • Systemic hypertension. hypertension also may complicate diabetes in that it may result in hypertensive retinal vascular changes superimposed on the preexisting diabetic retinopathy. 4% progress to the proliferative type. as evidenced by proteinuria and elevated BUN/creatinine levels.medscape. is an excellent predictor of the presence of retinopathy. The reason behind this is unclear. In 10-15 years. Of those with preexisting NPDR. • • Proper management of hyperlipidemia (elevated serum lipids) may result in less retinal vessel leakage and hard exudate formation. it may be logical to assume that the same principles also apply. PDR is rare within the first decade of diagnosis but increases to 14-17% by 15 years. no clinically significant retinopathy can be seen in the first 5 years after the initial diagnosis of diabetes. the incidence of diabetic retinopathy likewise increases with the duration of the disease. Independently. PDR was found in 3% of patients 11 or more years after the diagnosis. further compromising retinal blood flow. 41% have NPDR after 14-16 years. http://emedicine.

this medicine has been used to treat optic nerve or retinal neovascularization as well as rubeosis. In addition. an indirect ophthalmoscope.IDDM) should strive to maintain glycosylated hemoglobin levels of less than 7% to prevent or at the very least to minimize the long-term complications of DM. a grid pattern of laser burns is applied. This may be performed using a variety of delivery systems. Moderate intensity burns of 200-500 µm (gray-white burns) are placed 1 spot size apart. The strategy for treating macular edema depends on the type and extent of vessel leakage. reduces the rate of neovascularization. such as VEGF. except in areas of neovascularization where the entire frond is treated. This involves applying laser burns over the entire retina sparing the central macular area. which has a relatively low complication rate and a significant degree of success. Another theory is that PRP allows increased diffusion of oxygen from the choroid. including the slit lamp. Burns (100-200 µm) are placed 1 burn size apart covering the affected area. If it is necessary to complete both procedures at the same time. aspirin was not observed to influence the incidence of vitreous hemorrhage in patients who required it for cardiovascular disease (CVD) or other conditions. microaneurysms are treated directly with laser photocoagulation. This procedure is continued peripherally to achieve a total of 1200-1600 applications over 2-3 sessions. In cases where macular edema and PDR coexist. The presence of high-risk PDR is an indication for immediate treatment. Surgical Care The advent of laser photocoagulation in the 1960s and early 1970s provided a noninvasive treatment modality. first for the macular edema. • The Early Treatment for Diabetic Retinopathy Study (ETDRS) found that 650 mg of aspirin daily did not offer any benefit in preventing the progression of DM retinopathy. The exact mechanism by which PRP works is not entirely understood. The enhanced oxygen delivery o o o o . Additionally. in large phase III clinical trials. and the most frequent etiology of the vitreous hemorrhage was proliferative diabetic retinopathy. bevacizumab (Avastin) has been used to treat vitreous hemorrhage. o Application starts in a circumference of 500 µm from the disc and 2 disc diameters from the fovea to wall off the central retina. and then the PRP is spread over 3-4 sessions. and the EndoProbe. which. One theory is that destroying the hypoxic retina presumably decreases the production of vasoproliferative factors. intravitreal injections of ovine hyaluronidase (Vitrase) have been shown to be safe and to have modest efficacy for the clearance of severe vitreous hemorrhage. • More recently. If the edema is due to focal leakage. supplementing retinal circulation. • Recently. the PRP is applied initially to the nasal third of the retina. In cases where the foci of leakage are nonspecific. More than 70% of subjects in these studies had diabetes. in turn. including DM retinopathy. laser treatments are performed. • PRP is the preferred form of treatment of PDR.

o o o • Cryotherapy o When laser photocoagulation is precluded in the presence of an opaque media. The Diabetic Retinopathy Vitrectomy Study (DRVS) has recommended that vitrectomy be advised for eyes with vitreous hemorrhage that fails to resolve spontaneously within 6 months. to release tractional forces that pull on the retina. When treatment is delayed. tractional retinal detachment.also down-regulates vasoproliferative factor production and subsequent neovascularization. to ablate retinal tissue for oxygen demand to be decreased and to induce a chorioretinal adhesion. which could increase oxygen supply to the retina in the hope of preventing or downregulating the vasoproliferative response. to repair a retinal detachment. o http://emedicine. and to remove the scaffolding into which the neovascular complexes may grow. cryotherapy may be applied instead. The principles behind the treatment is basically the same. monitoring the status of the posterior segment by ultrasound is mandatory to watch for signs of macular detachment. Laser photocoagulation through indirect delivery systems or through the EndoProbe can be performed as an adjunctive procedure during surgery to initiate or continue laser treatment.medscape. mean of 4 mo) may result in a slightly greater recovery of vision in patients with type I diabetes. (Enlarge Image) . • Vitrectomy o Vitrectomy may be necessary in cases of long-standing vitreous hemorrhage (where visualization of the status of the posterior pole is too difficult). and combined tractional and rhegmatogenous retinal detachment. More uncommon indications include epiretinal membrane formation and macular dragging. Early vitrectomy ( <6 mo. such as in cases of cataracts and vitreous hemorrhage.com/article/1225210-treatment Multimedia Media file 1: New vessel formation on the surface of the retina (neovascularization elsewhere). The purpose of surgery is to remove the blood to permit evaluation and possible treatment of the posterior pole. that is.

medscape.Media file 2: An area of neovascularization that leaks fluorescein on angiography. (Enlarge Image) http://emedicine. Background . (Enlarge Image) Media file 5: Extensive fibrovascular proliferations within and around the optic disc. Diabetic. (Enlarge Image) Media file 3: Boat-shaped preretinal hemorrhage associated with neovascularization elsewhere.com/article/1225210-media Retinopathy. (Enlarge Image) Media file 4: Fibrovascular proliferations within the vitreous cavity.

but several theories have been postulated to explain the typical course and history of the disease. This led to the controversial practice of pituitary ablation to treat or prevent diabetic retinopathy in the 1950s. It was noted that diabetic retinopathy was reversed in women who had postpartum hemorrhagic necrosis of the pituitary gland (Sheehan syndrome). Section of Ophthalmology. Pathophysiology The exact mechanism by which diabetes causes retinopathy remains unclear. MD. Platelets and blood viscosity . Department of Surgery. PA. Adjunct Assistant Professor. cataracts. the most common and potentially most blinding of these complications is diabetic retinopathy. John A Burns School of Medicine Contributor Information and Disclosures Updated: Sep 7. glaucoma. iris neovascularization. MD. Growth hormone Growth hormone appears to play a causative role in the development and progression of diabetic retinopathy. Phillips Eye Institute John H Drouilhet. However. FACS. Ophthalmic complications of diabetes include corneal abnormalities. This technique has been abandoned because of numerous systemic complications and the discovery of the effectiveness of laser treatment. Department of Ophthalmology. Department of Ophthalmology. Past Chair.Abdhish R Bhavsar. Clinical Associate Professor. Consulting Staff. 2006 • • • • • • • • • Print This Email This Overview Differential Diagnoses & Workup Treatment & Medication Follow-up Multimedia References Keywords Introduction Background Diabetes mellitus (DM) is a major medical problem throughout the world. Diabetes causes an array of long-term systemic complications. Director of Clinical Research. which have considerable impact on both the patient and the society because it typically affects individuals in their most productive years. University of Hawaii. and neuropathies. Retina Center. University of Minnesota.

More extensive retinal hypoxia triggers compensatory mechanisms within the eye to provide enough oxygen to tissues. Venous caliber abnormalities. leading to hypoxia. which. contributes to the development of diabetic retinopathy. Intraretinal microvascular abnormalities (IRMA) represent either new vessel growth or remodeling of preexisting vessels through endothelial cell proliferation within the retinal tissues to act as shunts through areas of nonperfusion. predispose to sluggish circulation. Increased permeability of these vessels results in leakage of fluid and proteinaceous material. leading to fluid leakage and retinal thickening. increased platelet aggregation.The variety of hematologic abnormalities seen in diabetes. If the swelling and exudation would happen to involve the macula. endothelial damage. which clinically appears as retinal thickening and exudates. a diminution in central vision may be experienced. eventually leading to the loss of its primary function (ie. Intramural pericytes of retinal capillaries seem to be affected by this increased level of sorbitol. Macular edema is the most common cause of vision loss in patients with nonproliferative diabetic retinopathy (NPDR). in turn. Infarction of the nerve fiber layer leads to the formation of cotton-wool spots (CWS) with associated stasis in axoplasmic flow. and adhesion. which. such as venous beading. glucose into sorbitol. eventual closure of the retinal capillaries occurs. and dilation. which converts sugars into alcohol (eg. Increased levels of blood glucose are thought to have a structural and physiologic effect on retinal capillaries causing them to be both functionally and anatomically incompetent. in turn. but it also may complicate cases of proliferative diabetic retinopathy (PDR). As the disease progresses. such as increased erythrocyte aggregation. decreased RBC deformability. and focal capillary occlusion. Aldose reductase and vasoproliferative factors Fundamentally. especially permeability and flow. DM causes abnormal glucose metabolism as a result of decreased levels or activity of insulin. galactose to dulcitol). loops. Loss of function of pericytes results in weakness and eventual saccular outpouching of capillary walls. These microaneurysms are the earliest detectable signs of DM retinopathy. affects retinal blood dynamics. autoregulation of retinal capillaries). This is thought to activate protein kinase C (PKC). A persistent increase in blood glucose levels shunts excess glucose into the aldose reductase pathway in certain tissues. This leads to retinal ischemia. signify increasing hypoxia and almost always are seen bordering the areas of capillary nonperfusion. Another theory to explain the development of macular edema deals with the increased levels of diacylglycerol (DAG) from the shunting of excess glucose. it is not exclusively seen only in patients with NPDR. Ruptured microaneurysms (MA) result in retinal hemorrhages either superficially (flame-shaped hemorrhages) or in deeper layers of the retina (blot and dot hemorrhages). However. .

so does the degree of fibrous tissue formation. The new vessels break through and grow along the surface of the retina and into the scaffold of the posterior hyaloid face. retinal heterotropia. only one half receives appropriate eye care. the rate is even higher among certain ethnic groups.Further increases in retinal ischemia trigger the production of vasoproliferative factors that stimulate new vessel formation. it may exert tractional forces on the retina via these fibroglial connections. at least in part due to the increasing incidence of obesity and sedentary lifestyle. The extracellular matrix is broken down first by proteases. This cost does not compare to the cost in terms of loss of productivity and quality of life. it is not surprising that diabetic retinopathy is the leading cause of new blindness in persons aged 25-74 years in the United States. As the vitreous contracts. these vessels rarely cause visual compromise. Neovascularization most commonly is observed at the borders of perfused and nonperfused retina and most commonly occur along the vascular arcades and at the optic nerve head. However. However. the vessels may regress leaving only networks of avascular fibrous tissue adherent to both the retina and the posterior hyaloid face. and both tractional retinal detachments and retinal tear formation with subsequent detachment. and new vessels arising mainly from the retinal venules penetrate the internal limiting membrane and form capillary networks between the inner surface of the retina and the posterior hyaloid face. which leads to hemorrhage into the vitreous cavity or the preretinal space. as the density of the neovascular frond increases. This means that diabetes is responsible for 12% of blindness. Dietary changes involving diets with higher fat and carbohydrate intake as well as the increasing size of portions of food and drinks over the past several decades may also be responsible. These delicate vessels are disrupted easily by vitreous traction. Thus. Frequency United States Approximately 16 million Americans have diabetes. International The incidence of diabetes appears to be increasing throughout the world. Race . By themselves. with 50% of them not even aware that they have it. Mortality/Morbidity The treatment of diabetic retinopathy entails tremendous costs. In later stages. Traction may cause retinal edema. but it has been estimated that this represents only one eighth of the costs of social security payments for vision loss. Of those that know. responsible for more than 8000 cases of new blindness each year. These new blood vessels initially are associated with a small amount of fibroglial tissue formation. they are fragile and highly permeable.

Physical • Microaneurysms o Earliest clinical sign of diabetic retinopathy o o o o o • Secondary to capillary wall outpouching due to pericyte loss Appear as small red dots in the superficial retinal layers Fibrin and RBC accumulation in the microaneurysm lumen Rupture produces blot/flame hemorrhages May appear yellowish in time as endothelial cells proliferate and produce basement membrane Dot and blot hemorrhages o Occur as microaneurysms rupture in the deeper layers of the retina such as the inner o • • • nuclear and outer plexiform layers Appear similar to microaneurysms if they are small.Caused by the breakdown of the blood-retina barrier.000 new cases of macular edema are diagnosed annually.Splinter hemorrhages that occur in the more superficial nerve fiber layer Retinal edema and hard exudates . or visual acuity loss. Hispanic. patients are generally asymptomatic. including blurred vision. in the more advanced stages of the disease. however. A reported 75. patients may experience symptoms.An increased risk of diabetic retinopathy appears to exist in patients with Native American.No capillary perfusion Frequently bordered by microaneurysms and vascular hyperpermeability Venous loops. allowing leakage of serum proteins. . and protein from the vessels Cotton-wool spots o Nerve fiber layer infarction from occlusion of precapillary arterioles o o • Fluorescein angiography . distortion. Clinical History In the initial stages. and African American heritage. lipids. venous beading o Frequently adjacent to areas of nonperfusion o o • Reflects increasing retinal ischemia Most significant predictor of progression to PDR Intraretinal microvascular abnormalities o Remodeled capillary beds without proliferative changes o o • Collateral vessels that do not leak on fluorescein angiography Usually can be found on the borders of the nonperfused retina Macular edema o This condition is the leading cause of visual impairment in patients with diabetes. may need fluorescein angiography to distinguish between the two Flame-shaped hemorrhages .

o . In patients with type II diabetes. and 60% have NPDR after 16 years.Presence of at least 1 microaneurysm Moderate nonproliferative diabetic retinopathy o Presence of hemorrhages. the American Diabetes Association (ADA) has suggested that glycosylated hemoglobin levels of less than 7% (reflecting long-term glucose levels) should be the goal in all patients to prevent or slow down the onset of diabetes-related complications. Of patients with type II diabetes. Causes Risk factors • Duration of the diabetes o In patients with type I diabetes. 25-50% of patients show some signs of retinopathy. no clinically significant retinopathy can be seen in the first 5 years after the initial diagnosis of diabetes is made. and IRMA less than that of severe NPDR Severe nonproliferative diabetic retinopathy (4-2-1) o Hemorrhages and microaneurysms in 4 quadrants o o • Venous beading in at least 2 quadrants IRMA in at least 1 quadrant Mild NPDR reflects structural changes in the retina caused by the physiological and anatomical effects of diabetes. On the other hand. 41% have NPDR after 14-16 years. After 10-15 years. venous beading. the more advanced stages of NPDR reflect the increasing retinal ischemia setting up the stage for proliferative changes. o • Glucose control o The Diabetic Complications Control Trial (DCCT) has demonstrated that intensive glucose control reduced the incidence and the progression of diabetic retinopathy in patients with insulin-dependent diabetes mellitus (IDDM). 23% have NPDR after 11-13 years.o o Possibly due to functional damage and necrosis of retinal capillaries Clinically significant macular edema (CSME) is defined as any of the following:    • • Retinal thickening located 500 µm or less from the center of the foveal avascular zone (FAZ) Hard exudates with retinal thickening 500 µm or less from the center of the FAZ Retinal thickening 1 disc area or larger in size located within 1 disc diameter of the FAZ Mild nonproliferative diabetic retinopathy . This prevalence increases to 75-95% after 15 years and approaches 100% after 30 years of diabetes. and hard exudates o • Soft exudates. the incidence of diabetic retinopathy increases with the duration of the disease. microaneurysms. Although no similar trials for patients with non–insulin–dependent diabetes mellitus (NIDDM) have been completed.

is an excellent predictor of the presence of retinopathy. elucidated pathophysiologic mechanisms and described clinical findings through direct patient management observations and animal . Consulting Staff. This vascular condition involves every organ system. Nader Moinfar. as evidenced by proteinuria and elevated BUN/creatinine levels. • Systemic hypertension.medscape. Pregnant women without any diabetic retinopathy run a 10% risk of developing NPDR during their pregnancy. Assistant Professor. Ocular involvement was first described in 1859 by Liebreich in the setting of malignant hypertension. Consulting Staff. Independently. hypertension also may complicate diabetes in that it may result in hypertensive retinal vascular changes superimposed on the preexisting diabetic retinopathy. PC Bradley M Hughes. Associated Retinal Consultants.com/article/1225122-overview Hypertension Kean Theng Oh. • • Proper management of hyperlipidemia (elevated serum lipids) may result in less retinal vessel leakage and hard exudate formation. This probably is due to the fact that both conditions are caused by DM-related microangiopathies such that the presence and severity of one reflects that of the other. Evidence suggests that aggressive treatment of the nephropathy may have a beneficial effect on the progression of diabetic retinopathy and neovascular glaucoma. http://emedicine. in the setting of diabetic nephropathy. Vitreoretinal Department. 2008 • • • • • • • • Print This Email This Overview Differential Diagnoses & Workup Treatment & Medication Follow-up References Keywords Introduction Background Hypertension is a leading cause of morbidity and mortality worldwide.• Renal disease. Retina and Vitreous Service. correlates well with the presence of retinopathy. Of those with preexisting NPDR. over the course of the 1970s and 1980s. Hayreh. further compromising retinal blood flow. University of Arkansas for Medical Sciences. 4% progress to the proliferative type. MD. The reason behind this is unclear. Department of Ophthalmology. MD. MD. Magruder Eye Institute Contributor Information and Disclosures Updated: Nov 17.

Retinal arterioles and capillaries are similar in anatomy to cerebral vessels in that they exhibit autoregulatory mechanisms and tight junctions to maintain the blood ocular barrier. The mechanisms and physical findings of hypertensive changes in the eye are discussed in this article. FIPTs are not cotton-wool spots.models. malignant increase in blood pressure. subsequently. and optic nerve. Both acute and chronic changes may manifest in the eyes. a symptomatic patient may be referred to the ophthalmologist for visual changes due to hypertensive changes. Optic nerve head vessels exhibit intermediary characteristics with autoregulation but an incompetent blood-ocular barrier as a result of the peripapillary choroidal vessels. associated with major arteriole vessels Not associated with capillary obliteration. choroid. but together represent the clinical picture of the ocular response to systemic hypertension. Pathophysiology The pathophysiology of hypertensive ocular changes can be subdivided into acute changes from malignant hypertension and chronic changes from long-term systemic hypertension.  Specifically. This results in breakdown of the blood retinal barrier allowing transudation and accumulation of macromolecules. Choroidal arterioles and capillaries have fenestrations (ie. ocular effects of hypertension are based on its effects on the ocular vasculature and consequences therefrom. no blood ocular barrier) and do not exhibit autoregulation. hyperfluoresce and leak on fluorescein angiography May be related to dilation of terminal arterioles and breakdown of autoregulatory mechanisms due to acute. Ocular blood vessels have different characteristics based on their anatomical location that. dictate their response to elevated blood pressure. Ocular changes can be the initial finding in an asymptomatic patient necessitating a primary care referral. Fundamentally. . Malignant arterial hypertension • Hypertensive retinal changes (hypertensive retinopathy) o Changes in the retinal circulation in the acute phase of hypertension primarily involve the terminal arterioles rather than the main retinal arterioles. small white lesions deep in the retina. each of these anatomical regions respond differently. On the other side. Main retinal arteriole changes are seen and recognized as a response to chronic systemic hypertension. Focal intraretinal periarteriolar transudates (FIPTs) o       First described by Hayreh Only observed in malignant arterial hypertension One of the earliest lesions seen in the retina as a consequence of malignant hypertension Focal. oval. Because of the vascular differences between the retina.

Hayreh observed that the presence of a NSRD was correlated to the degree of choroidal circulation disruption. and collaterals. Hypertensive choroidopathy o Related to the anatomical and functional differences found in the choroidal vasculature as compared to the retinal vasculature         • Sympathetic innervation makes terminal arterioles more susceptible to vasoconstriction. related to the distribution of the radial peripapillary capillaries.  Fluorescein angiography appearance is hypofluorescence due to nonperfusion and capillary dropout.o Inner retinal ischemic spots (cotton-wool spots)   Hayreh used the term inner retinal ischemic as a more descriptive term than cotton-wool spots. o  Last approximately 3-6 weeks before fading away Other acute retinal changes   Capillary obliteration results in development of microaneurysms. o Focal white spots at the level of retinal pigment epithelium similar to FIPTs Serous retinal detachments Preferentially affects the macular region causing neurosensory retinal detachments (NSRD) and cystoid macular edema Ischemic damage to the retinal pigment epithelium leads to breakdown of the blood retinal barrier. Fenestrations in the capillaries and the consequent lack of a blood ocular barrier allow free passage of macromolecules. Retinal pigment epithelial changes Acute ischemic changes in the choriocapillaris and overlying retinal pigment epithelium results in acute focal retinal pigment epithelium lesions. Hypertensive optic neuropathy o Anatomical differences in optic nerve head blood supply   o Optic disc vessels possess autoregulation.  • Macular edema can develop as a consequence of hypertensive choroidopathy. Lacks a competent blood retinal barrier due to peripapillary choroidal perfusion Optic disc edema is a primary manifestation of hypertensive optic neuropathy. shunt vessels. o No autoregulation increases susceptibility to elevated perfusion pressures. Fluffy white lesion at the level of the nerve fiber layer found more commonly in the posterior pole. Retinal hemorrhages: Hayreh noted that the development of blot retinal hemorrhages are neither an early nor a conspicuous finding associated with malignant hypertension.  Ischemic cause for optic disc edema .

 Blood supply to the optic nerve is via posterior ciliary arteries and peripapillary choroidal vessels. and acceleration in atherosclerosis will contribute to increased morbidity and mortality. . Mortality/Morbidity Cardiac. and ophthalmic sequelae lead to morbidity and mortality. neurologic. Systemic hypertension accelerates progression of diabetic retinopathy and increases the risk of arterial and venous occlusion. According to Ryan. 58 million adults in the United States have elevated blood pressure or are taking antihypertensive medications. accounting for 6% of all deaths. such as shunt vessels and microaneurysms o Retinal pigment epithelial changes    • Diffuse pigmentary granularity and moth-eaten appearance Elschnig spots: Areas of retinal pigment epithelium clumping and atrophy that form from the focal acute white retinal pigment epithelium lesions Triangular patches of atrophy as a result of occlusion of a larger caliber choroidal vessel Optic nerve: Optic disc pallor Frequency United States According to the Centers for Disease Control and Prevention and National Center for Health Statistics. hypertension has been rated the fourth largest mortality risk in the world. 30% will have early cardiovascular damage.1% of the US population is estimated to have hypertension. Chronic hypertensive changes • Retina o Arteriolosclerosis: Localized or generalized narrowing of vessels  o o o o • Choroid Copper wiring and silver wiring of arterioles  Arteriovenous-nicking Retinal hemorrhages Nerve fiber layer losses Increased vascular tortuosity Remodeling changes due to capillary nonperfusion. renal. Vasoconstriction and choroidal ischemia in the setting of malignant hypertension result in optic disc edema and axoplasmic flow stasis. 23. International Worldwide. Of affected individuals.

It is composed of atherosclerosis (changes in the intima). Clinical History Most patients are asymptomatic. visible on ophthalmoscopy as a phenomenon known as sheathing of the vessels. In the retina.Race Hypertension is more common in the African American population. medial hypertrophy.3% of men and 20. symptomatic patients most commonly present with headaches and blurred vision. • Light reflex change o According to Spencer. Sex According to the Centers for Disease Control and Prevention and National Center for Health Statistics. the entire vessel appears opaque (pipe stem o . Advanced sclerosis leads to increased optical density of the vessel wall. arteriosclerosis is defined as hardening and thickening of arteries. The latter is characterized by intimal hyalinization. atherosclerosis and arteriolosclerosis predominate. Progression of sclerosis and hyalinization causes the reflex to be more diffuse and the retinal arterioles to become red-brown. o According to Duane's Ophthalmology. which evolves from the accumulation of fat-laden cells between the intimal elastic lamella and the endothelium of the vessel wall. and arteriolosclerosis (changes in the intima with or without media).8% of women have hypertension.1 Initially.3% of women older than 75 years had hypertension. However. When the anterior surface becomes involved. 25. Approximately 30% of the African American population is estimated to have hypertension as opposed to 20% of Caucasians. and endothelial hyperplasia. However. medial sclerosis. the increased thickness of the vessel walls causes the reflex to be more diffuse and less bright. The former is characterized by an atheroma. This is known as copper wiring. the normal light reflex of the retinal vasculature is formed by the reflection from the interface between the blood column and vessel wall. no racial predilection for hypertensive retinopathy has been noted. Age According to the Centers for Disease Control and Prevention and National Center for Health Statistics. Physical • Arteriosclerosis o Arteriosclerotic changes are chronic changes as a result of systemic hypertension.2% of men older than 75 years and 77. 64.

This change in length deflects the veins at the common sheath and changes the course of the vein (Salus sign). the original crossing angle. Retinal hemorrhages: In addition to microaneurysms. causing hourglass constrictions on both sides of the crossing and aneurysmal-like swellings. which occurs when a significant elevation of blood pressure has persisted for an appreciable period. the degree of vascular thickening. Stasis engorgement of the capillaries may lead to anoxia and poor nutrition. Histologically. The patency of such vessels has been demonstrated by fluorescein angiography. Mimatsu asserts that the crossing changes were due to sclerotic thickening of the wall of the venule and not by compression by the arteriole. Thickening of the basement membrane and the media of the arteriole in hypertension impinge on the vein and cause the crossing phenomenon. which can become permanent with fibrosis. and the pressure differential influence this phenomenon. it produces a silver-wire vessel. A relationship has been noted between the narrowing of the caliber of the arteriole and the height of the diastolic pressure. which contributes to microaneurysm formation. Although the deposits assume many shapes and o o o . Retinal and macular edema Retinal lipid deposits: Absorption of the plasma component of retinal edema leads to protein accumulation.sheathing). o o • Arterial narrowing and straightening: Sclerosis may shorten or elongate retinal arterioles with the branches coming off at right angles. Histologically. Spencer speculates that either edema in and around the vessel wall. Spencer notes findings of various authors. which leads to retinal hemorrhages. According to Albert and Jakobiec. Streak hemorrhages located in the nerve fiber layer predominate over the blot hemorrhages located deeper in the outer plexiform layer. o o • AV nicking (the Gunn sign): Impeded circulation results in a dilated or swollen vein peripheral to the crossing. When sheathing encircles the wall. or vascular spasm leads to focal narrowing. These are chronic changes due to systemic hypertension.2 • Extravascular retinal lesions o Microaneurysms: Postulated to occur at localized areas of capillary wall weakness. to include the following:1 o Ikui noted that arteriole and venous basement membranes are adherent with shared collagen fibers at the crossing points. microaneurysms are most visible by angiography. Focal narrowing occurs from spasm of local areas of the vascular musculature. there is accumulation of edema residue and lipid-containing macrophages. • Attenuation o Generalized attenuation of the arterioles occurs as a result of diffuse vasospasm. loss of endothelial integrity leads to extravasation of plasma. Increased intraluminal pressure either in the retinal arterioles or in the central artery of the retina causes narrowing of the arterioles. Seitz attributed the crossing phenomenon to vascular sclerosis and perivascular glial cell proliferation and not to venous compression.

Department of Family Practice. Other factors. The retinopathy may also be more severe and more progressive when diabetes and hypertension are associated. 2007 • • • • • • • • Print This Email This Overview Differential Diagnoses & Workup Treatment & Medication Follow-up References Keywords Introduction Background Diabetes mellitus (DM) is a multisystem disease with both biochemical and anatomical consequences. University Hospital of Brooklyn Miriam T Vincent. State University of New York Downstate Medical Center.com/article/1201779-overview Diabetes Mellitus. It is a chronic disease of carbohydrate. FAAFM. PhD. and protein metabolism caused by the lack of insulin. Professor and Chair. and this appearance is due to the radially oriented nerve fiber layer of Henle. the macular star is the most predominant appearance. However. Causes In general. These changes may be seen in other diseases with vascular risk factors.medscape. such as hyperlipidemia. MD. may make the retinopathy worse as well http://emedicine. those with type 1 DM generally are not obese and may present initially with diabetic ketoacidosis (DKA). the degree and the duration of hypertension are the primary determinants of hypertensive retinopathy. Assistant Professor. State University of New York Downstate Medical Center Contributor Information and Disclosures Updated: Nov 2. Consulting Staff. Department of Family Medicine.appear in many parts of the retina. especially in those in their late 30s and early 40s. insulin is functionally absent because of the destruction of the beta cells of the pancreas. fat. In type 1 diabetes. such as diabetes. Type 1 DM occurs most commonly in juveniles but can occur in adults. Unlike people with type 2 DM. . Department of Family Medicine. MD. the changes described above are not unique for hypertension. • • Inner retinal ischemic spots (cotton-wool spots): See Pathophysiology. Type 1 Aneela Naureen Hussain. Focal intraretinal periarteriolar transudate (FIPT): See Pathophysiology.

Two million adolescents (or 1 in 6 overweight adolescents) aged 12-19 years have prediabetes status. While an estimated 14. 1. decrease hyperglucagonemia.22% of all people in this age group. who have diabetes. causing insulin deficiency. 6. or 0.8 million children and adults in the United States. HLA-DQs are considered specific markers of type 1 DM susceptibility. Approximately 85% of patients have circulating islet cell antibodies.000 new cases every year. Type 1 DM is an autoimmune disease. In people aged 20 years or older. or 7% of the population. . autoimmunity is considered the major factor in the pathophysiology of type 1 DM. unfortunately. Environmental agents that have been hypothesized to induce an attack on beta cell function include viruses (eg. The pancreas shows lymphocytic infiltration and destruction of insulin-secreting cells of the islets of Langerhans. Patients need exogenous insulin to reverse this catabolic condition.000 people younger than 18 years. According to the American Diabetes Association. prevent ketosis. Frequency United States Roughly 5-15% of all cases of diabetes are type 1 DM. mumps. 176.Pathophysiology Type 1 DM is a catabolic disorder in which circulating insulin is very low or absent. Coxsackie B4). and physicians diagnose 10. and Addison disease. and the pancreatic beta cells fail to respond to all insulin-secretory stimuli. One theory regarding the etiology of type 1 DM is that it results from damage to pancreatic beta cells from an infectious or environmental agent. Recent evidence suggests a role for vitamin D in the pathogenesis and prevention of diabetes mellitus. Approximately 1 million Americans have type 1 DM.5 million new cases of diabetes were diagnosed in 2005. and normalize lipid and protein metabolism. Currently. with a yearly incidence of 15 cases per 100. It triggers the immune system in a genetically susceptible individual to develop an autoimmune response against altered pancreatic beta cell antigens or molecules in beta cells that resemble a viral protein. and cytotoxins. have diabetes.6 million have been diagnosed. plasma glucagon is elevated. Prevalence is increased in patients with other autoimmune diseases.2 million people (or nearly one-third) are undiagnosed. Fifty-four million people are prediabetes status. and the majority also have detectable anti-insulin antibodies before receiving insulin therapy. In people younger than 20 years. rubella.500 cases. Hashimoto thyroiditis. About one in every 400-600 children and adolescents has type 1 DM. there are 20. such as Graves disease. toxic chemicals. Approximately 95% of patients with type 1 DM have either human leukocyte antigen (HLA)-DR3 or HLA-DR4. exposure to cow's milk in infancy. It is the most common metabolic disease of childhood. Most islet cell antibodies are directed against glutamic acid decarboxylase (GAD) within pancreatic B cells.

Age Type 1 DM usually starts in children aged 4 years or older. It is not unusual for type 1 DM to present with ketoacidosis. The disease onset may be sudden. with the presentation of an infection. a relatively high incidence exists in people in their late 30s and early 40s. with less than 1% of all people with diabetes. and autonomic and peripheral neuropathy. with the peak incidence of onset at age 1113 years. and blurred vision. chronic renal disease. ie. peripheral vascular disease with gangrene of lower limbs. approximately 20% of the total number of people with DM).International Scandinavia has the highest prevalence rates for type 1 DM (ie. Race Type 1 DM is more common among non-Hispanic whites. polydipsia. Some of these differences may relate to definitional issues and the completeness of reporting. The annual financial cost from diabetes overall exceeds $100 billion. reduced visual acuity and blindness. it may occur de novo or develop with the stress of illness or surgery. cerebral vascular disease. and polyphagia. nausea. coinciding with early adolescence and puberty. Clinical History The most common symptoms of type 1 diabetes mellitus (DM) are polyuria. almost $1 of every $7 dollars of US health expenditures in terms of medical care and loss of productivity. It is comparatively uncommon among Asians. along with lassitude. Mortality/Morbidity Type 1 DM is associated with a high morbidity and premature mortality due to complications. As a result of these complications. all of which are due to the hyperglycemia itself. when it tends to present in a less aggressive manner. followed by African Americans and Hispanic Americans. Also. while China and Japan have the lowest prevalence rates. Advances in treatment that permit tight glycemic control and control of comorbidities (hyperlipidemia) can greatly reduce the incidence of microvascular and macrovascular complications. An explosive onset of symptoms in a young lean patient with ketoacidosis always has been considered diagnostic of type 1 DM. early hyperglycemia without ketoacidosis and gradual onset of ketosis. Sex Type 1 DM is more common in men than in women. people with diabetes have an increased risk of developing ischemic heart disease. .

and ascending neuropathy.medscape. eg. physical examination findings are usually normal.• • • • • • • Polyuria and thirst: Polyuria is due to osmotic diuresis secondary to hyperglycemia. hypotension. including the accumulation of sorbitol in peripheral sensory nerves due to sustained hyperglycemia. however. Peripheral neuropathy: This presents as numbness and tingling in both hands and feet. dehydration. Persistent abdominal pain may indicate another serious abdominal cause of DKA. Extragenetic factors also may contribute http://emedicine. Fatigue and weakness: This may be due to muscle wasting from the catabolic state of insulin deficiency. patients should be examined every 3 months for macrovascular and microvascular complications. and triglycerides. Chronic gastrointestinal symptoms in the later stage of diabetes are due to visceral autonomic neuropathy. • Symptoms at the time of the first clinical presentation can usually be traced back several days to several weeks. Blurred vision: This also is due to the effect of the hyperosmolar state on the lens and vitreous humor. in some cases. Physical In new cases of diabetes. Causes The etiology of type 1 DM has a strong genetic component. and hypokalemia. Thirst is due to the hyperosmolar state and dehydration. Gastrointestinal symptoms: Nausea. or even years. Muscle cramps: This is due to electrolyte imbalance. In established cases. except in DKA. causing right upper quadrant pain. beta cell destruction may have started months. They should have funduscopic examination for retinopathy and monofilament testing for peripheral neuropathy. It is bilateral. abdominal discomfort or pain. Nevertheless. Acute fatty liver may lead to distention of the hepatic capsule. Nocturnal enuresis: Severe enuresis secondary to polyuria can be an indication of onset of diabetes in young children.com/article/117739-overview Growth Hormone Deficiency . • • Patients may maintain their normal weight or exhibit wasting. altered mental status are present. depending on the interval between the onset of the disease and initiation of treatment. Glucose and its metabolites cause dilation of the lens. and change in bowel movements may accompany acute DKA. before the onset of clinical symptoms. proteins. wherein signs of Kussmaul respiration. and. identical twins have a concordance rate for type 1 DM of less than 50%. symmetric. pancreatitis. Polyphagia with weight loss: The weight loss with a normal or increased appetite is due to depletion of water and a catabolic state with reduced glycogen. hypovolemia. in a glove and stocking pattern. which results from many factors. altering its normal focal length.

FACP.000 live children. lipolytic. 5 GHD results in alterations in the physiology of different systems of the body. bone density. Consultant. to restore normal body composition. Saudi Arabia Contributor Information and Disclosures Updated: Jun 2. both of which are produced by the hypothalamus. About 20. therapy promotes linear growth and restores body composition. including the epiphyseal growth plate. The hormone's secretion is stimulated by growth hormone – releasing hormone (GHRH) and is inhibited by somatostatin.000 new children are diagnosed annually as candidates for this treatment. while adults have reduced physical performance and impaired psychological well-being. which is produced by the liver and other target tissues. In children. King Abdulaziz National Guard Medical Center. Division of Endocrinology and Metabolism. Department of Internal Medicine. and to improve the quality of life. .000 children per year receive growth hormone therapy. Growth hormone's diverse metabolic actions also include anabolic.1 Children usually present with short stature. and exercise performance.000 to 1 per 10. 3 Related eMedicine topics: Growth Failure Growth Hormone Deficiency [Pediatrics: General Medicine] Growth Hormone Replacement in Older Men Short Stature Pathophysiology Growth hormone promotes linear growth by regulating the endocrine and paracrine production of insulinlike growth factor 1 (IGF-1).Mohsen S Eledrisi. 5 Frequency United States The incidence of short stature associated with severe childhood GHD has been estimated in several studies to range between 1 per 4. 2008 Introduction Background The somatotroph cells of the anterior pituitary gland produce growth hormone. manifesting in increased subcutaneous visceral fat and decreased muscle mass. the goals are to improve conditioning and strength. and diabetogenic effects. depending on the age of onset. The clinical manifestations of growth hormone deficiency (GHD) are variable.4.4. MD. The goals of growth hormone therapy differ in children and adults. and approximately 4. FACE. in adults.2.

This increased mortality is probably attributable to premature cardiovascular disease.8 Consider the possibility of hypopituitarism in patients with neonatal hypoglycemia. cleft palate.The exact prevalence of adult-onset GHD is not known.000 adults have GHD. septo-optic dysplasia. the age of presentation varies with respect to the time of onset and the degree of GHD. 3: o Reduced bone mineral density and increased risk of osteoporotic bone fractures o o o o o o • Impaired cardiac function Central obesity Increased insulin sensitivity Reduced exercise capacity Emotional disturbances Decreased quality of life Epidemiologic data suggest that adults with GHD have reduced life expectancy. solitary central incisor). prolonged jaundice. International No data are available. • In adults.000 new adult patients are diagnosed annually. whereas those with lesser degrees of deficiency present at older ages. 7 Age • In children. Related eMedicine topic: Pituitary Tumors Clinical History • Children o Growth failure after a period of normal growth is a characteristic feature of GHD that presents during childhood. midline facial defects (eg. the age of presentation often coincides with the discovery of pituitary tumors. Mortality/Morbidity • Adult GHD is associated with the following problems2. Children present with short stature and low growth velocity for age and pubertal stage.6. and about 6. Approximately 35. usually between the fourth and fifth decades of life. male micropenis (not necessarily related to gonadotropin o . Children with complete absence of growth hormone secretion usually present before reaching the age of 3 years.

with a prominent forehead and depressed midfacial development. or they may have previously suffered a head trauma.4 o o Related eMedicine topics: Hypopituitarism [Emergency Medicine] Hypopituitarism [Pediatrics: General Medicine] Hypopituitarism (Panhypopituitarism) Physical • Children o o o o o o o • Adults The standing height standard deviation score is usually below -2. Some persons with GHD are entirely asymptomatic. Reduced lean body mass and increased weight. decreased strength and exercise tolerance. The face is immature. visual disturbances). Increased subcutaneous fat is present. headaches. especially around the trunk. and gonadal hormones The symptoms of GHD in adults are often nonspecific. adrenal. such as thyroid. In males. the phallus may be small. . Growth velocity is below the 10-25th percentile. Reported symptoms may include low energy level. with body fat mass predominantly in the abdominal region Thin and dry skin Cool peripheries Poor venous access Reduced muscle mass and strength and reduced exercise performance Depressed affect Labile emotions o o o o o o o Causes • Causes of GHD in children can be divided into 3 categories. Dentition is delayed. • Adults9 o Adults with GHD usually have a history of pituitary tumors that may have been treated with surgery or radiation. and impaired sleep. social isolation. decreased libido. histiocytosis X. and symptoms of a mass lesion in the hypothalamic-pituitary region (eg. which reflects growth deceleration. emotional lability. previous cranial irradiation. anxiety. increased weight or difficulty losing weight. Some patients will also have manifestations of deficiency of other pituitary hormones. The average age of pubertal onset is delayed in males and females.deficiency).

com/article/120767-overview . tuberculosis. and infiltrative diseases.These include trauma. which is usually o caused by a pituitary tumor. no clear etiology can be identified. Causes of GHD in adults o Pituitary disease . including sarcoidosis. hemochromatosis. hemochromatosis. Acquired conditions      Tumors of the hypothalamic-pituitary region . or X-linked defects or a mutation or deletion in the growth hormone gene or o in the GHRH. histiocytosis X.Craniopharyngioma is the most common tumor. such as sarcoidosis. or by radiation therapy for the tumor.In many cases. Cranial irradiation Infiltrative diseases. tuberculosis. including autosomal-recessive.medscape. lymphocytic hypophysitis. histiocytosis X. by surgery. autosomal-dominant. Idiopathic . and lymphocytic hypophysitis Trauma o • Hypoxic insult Idiopathic . no cause can be found o http://emedicine.In rare instances. Other causes .o Congenital conditions        Defective pituitary development that leads to pituitary aplasia Empty sella Encephalocele Midline defects Septo-optic dysplasia Panhypopituitarism Genetic abnormalities.More than 90% of patients have pituitary disease.

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