Ординатура / Офтальмология / Английские материалы / Textbook of Vitreoretinal Diseases and Surgery_Natarajan, Hussain_2008
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Textbook of Vitreoretinal Diseases and Surgery
35.Thumann G, Bartz-Schmidt KU, El Bakri H, et al. Transplantation of autologous iris pigment epithelium to the subretinal space in rabbits. Transplantation 1999; 68 (2):195-201.
36.Thumann G, Aisenbrey S, Schraermeyer U, et al. Transplantation of autologous iris pigment epithelium after removal of choroidal neovascular membranes. Arch Ophthalmol 2000; 118 (10):1350-5.
37.Kano T, Abe T, Tomita H, Sakata T, Ishiguro S, Tamai M. Protective effect against ischemia and light damage of iris pigment epithelial cells transfected with the BDNF gene. Invest Ophthalmol Vis Sci 2002; 43 (12): 3744-53.
38.Hojo M, Abe T, Sugano E, et al. Photoreceptor protection by iris pigment epithelial transplantation transduced with AAV-mediated brain-derived neurotrophic factor gene. Invest Ophthalmol Vis Sci 2004; 45 (10): 3721-6.
39.Zhao X, Das AV, Thoreson WB, et al. Adult corneal limbal epithelium: a model for studying neural potential of nonneural stem cells/progenitors. Dev Biol. 2002; 250 (2): 317-31.
40.Zhao X, Das AV, Bhattacharya S, et al. Derivation of neurons with functional properties from adult limbal epithelium: implications in autologous cell therapy for photoreceptor degeneration. Stem Cells. 2008; 26 (4): 939-49.
41.Seigel GM, Sun W, Salvi R, Campbell LM, Sullivan S, Reidy JJ. Human corneal stem cells display functional neuronal properties. Mol Vis 2003; 9: 159-63.
42.Hirano M, Yamamoto A, Yoshimura N, et al. Generation of structures formed by lens and retinal cells differentiating from embryonic stem cells. Dev Dyn 2003; 228 (4): 664-71.
43.Aoki H, Hara A, Nakagawa S, et al. Embryonic stem cells that differentiate into RPE cell precursors in vitro develop into RPE cell monolayers in vivo. Exp Eye Res 2006; 82 (2): 265-74.
44.Zhao X, Liu J, Ahmad I. Differentiation of embryonic stem cells into retinal neurons. Biochem Biophys Res Commun 2002; 297 (2): 177-84.
45.Ikeda H, Osakada F, Watanabe K, et al. Generation of Rx+/Pax6+ neural retinal precursors from embryonic stem cells. Proc Natl Acad Sci USA 2005; 102 (32):11331-6.
46.Banin E, Obolensky A, Idelson M, et al. Retinal incorporation and differentiation of neural precursors derived from human embryonic stem cells. Stem Cells 2006; 24 (2): 246-57.
47.Lamba DA, Karl MO, Ware CB, Reh TA. Efficient generation of retinal progenitor cells from human embryonic stem cells. Proc Natl Acad Sci USA 2006;103 (34):12769-74.
48.Ueno M, Matsumura M, Watanabe K, et al. Neural conversion of ES cells by an inductive activity on human amniotic membrane matrix. Proc Natl Acad Sci USA 2006; 103 (25): 9554-9.
49.Osakada F, Ikeda H, Mandai M, et al. Toward the generation of rod and cone photoreceptors from mouse, monkey and human embryonic stem cells. Nat Biotechnol 2008; 26 (2): 215-24.
50.Watanabe K, Kamiya D, Nishiyama A, et al. Directed differentiation of telencephalic precursors from embryonic stem cells. Nat Neurosci 2005; 8 (3): 288-96.
51.Meyer JS, Katz ML, Maruniak JA, Kirk MD. Embryonic stem cell-derived neural progenitors incorporate into degenerating retina and enhance survival of host photoreceptors. Stem Cells 2006; 24 (2): 274-83.
52.Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH. Viable offspring derived from fetal and adult mammalian cells. Nature 1997; 385 (6619): 810-3.
53.Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126 (4): 663-76.
54.Okita K, Ichisaka T, Yamanaka S. Generation of germline-competent induced pluripotent stem cells. Nature 2007; 448 (7151): 313-7.
55.Arnhold S, Klein H, Semkova I, Addicks K, Schraermeyer U. Neurally selected embryonic stem cells induce tumor formation after long-term survival following engraftment into the subretinal space. Invest Ophthalmol Vis Sci 2004;45(12):4251-5.
56.Sanchez-Ramos J, Song S, Cardozo-Pelaez F, et al. Adult bone marrow stromal cells differentiate into neural cells in vitro. Exp Neurol 2000;164(2):247-56.
57.Chan-Ling T, Baxter L, Afzal A, et al. Hematopoietic stem cells provide repair functions after laser-induced Bruch’s membrane rupture model of choroidal neovascularization. Am J Pathol 2006;168(3):1031-44.
58.Atmaca-Sonmez P, Li Y, Yamauchi Y, et al. Systemically transferred hematopoietic stem cells home to the subretinal space and express RPE-65 in a mouse model of retinal pigment epithelium damage. Exp Eye Res 2006;83(5):12951302.
59.Kicic A, Shen WY, Wilson AS, Constable IJ, Robertson T, Rakoczy PE. Differentiation of marrow stromal cells into photoreceptors in the rat eye. J Neurosci 2003;23(21):7742-9.
60.Arnhold S, Heiduschka P, Klein H, et al. Adenovirally transduced bone marrow stromal cells differentiate into pigment epithelial cells and induce rescue effects in RCS rats. Invest Ophthalmol Vis Sci 2006;47(9):4121-9.
61.Asahara T, Masuda H, Takahashi T, et al. Bone marrow origin of endothelial progenitor cells responsible for
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postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 1999;85(3):221-8. |
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Cell Therapy in Retinal Diseases
62.Otani A, Kinder K, Ewalt K, Otero FJ, Schimmel P, Friedlander M. Bone marrow-derived stem cells target retinal astrocytes and can promote or inhibit retinal angiogenesis. Nat Med 2002;8(9):1004-10.
63.Otani A, Dorrell MI, Kinder K, et al. Rescue of retinal degeneration by intravitreally injected adult bone marrowderived lineage-negative hematopoietic stem cells. J Clin Invest 2004;114(6):765-74.
64.Nishida A, Takahashi M, Tanihara H, et al. Incorporation and differentiation of hippocampus-derived neural stem cells transplanted in injured adult rat retina. Invest Ophthalmol Vis Sci 2000;41(13):4268-74.
65.Sakaguchi DS, Van Hoffelen SJ, Theusch E, et al. Transplantation of neural progenitor cells into the developing retina of the Brazilian opossum: an in vivo system for studying stem/progenitor cell plasticity. Dev Neurosci 2004;26(5-6):336-45.
66.Goodwin HS, Bicknese AR, Chien SN, Bogucki BD, Quinn CO, Wall DA. Multilineage differentiation activity by cells isolated from umbilical cord blood: expression of bone, fat, and neural markers. Biol Blood Marrow Transplant 2001;7(11):581-8.
67.Buzanska L, Machaj EK, Zablocka B, Pojda Z, Domanska-Janik K. Human cord blood-derived cells attain neuronal and glial features in vitro. J Cell Sci 2002;115(Pt 10):2131-8.
68.Koike-Kiriyama N, Adachi Y, Minamino K, et al. Human cord blood cells can differentiate into retinal nerve cells. Acta Neurobiol Exp (Wars) 2007;67(4):359-65.
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Textbook of Vitreoretinal Diseases and Surgery
Introduction
As the diabetic population burgeons globally, so will the unusual presentations of the disease become increasingly manifest. The retinopathy of diabetes will be no exception to this rule. This essay attempts to chronicle the various atypical manifestations of diabetic retinopathy (DR) hitherto reported. The protean manifestations can be due to the inherent variability of DR, systemic and ocular diseases that may modify its course or as a result of exceptional novel features.
The Inherent Variability of Diabetic Retinopathy
FLORID DIABETIC RETINOPATHY
A rare complication, occurring in less than 1% of cases of proliferative diabetic retinopathy (PDR), florid DR is a rapidly progressing, bilateral, severely ischemic retinopathy with poor vision that usually occurs in young, type 1 poorly controlled diabetic patients.1-3 Extensive panretinal photocoagulation with early vitrectomy when mandated will help improve their visual outcome.2,3
FEATURELESS RETINA
Featureless retina is a unique, rare type of PDR wherein retinal neovascularization may present without the characteristic preproliferative background retinal lesions such as microaneurysms, hemorrhages, cotton-wool spots and intraretinal microvascular abnormalities. The absence of these features may be explained by the presence of extensive areas of capillary non-perfusion seen in these cases which leads to the disappearance of these lesions in these severely ischemic zones.4 Although it may appear atrophic at first glance, fluorescein angiography may reveal undetected areas of neovascularization with extensive capillary non-perfusion (Figures 3-1A and B).
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FIGURES 3-1A AND B: (A) Fundus photograph of an eye that apparently looks like a case of mild nonproliferative |
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diabetic retinopathy. (B) Fluorescein angiogram of the eye reveals extensive capillary nonperfusion and leakage from |
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neovascular tissue |
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PERIPHERALABNORMALITIES IN DIABETIC RETINOPATHY |
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Occasionally, cases of diabetic retinopathy (2-3%) show predominant involvement of the periphery |
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with relative sparing of the posterior pole.5,6 Such patients are at risk of developing peripheral |
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Atypical Manifestations of Diabetic Retinopathy
FIGURE 3-2: Fundus photograph of an eye with massive deposition of hard exudates at the posterior pole
neovascularization that may be difficult to discern clinically (Figure 3-2). Neovascularization of the disc may occur despite adequate perfusion of the area centralis.7 A fibrovascular ridge at the ora was reported intraoperatively, in a series from Japan, in about half the eyes with PDR and peripheral avascularity. The ridge was noted to be strongly associated with the presence of neovascularization of the anterior segment.8,9 Peripheral new vessels were found emanating from the choroid by Ishibashi
et al in an eye with PDR enucleated for neovascular glaucoma.10 |
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DIABETIC DISC EDEMA |
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Diabetic papillopathy (DP) is an edema of the optic nerve head that is typically transient, usually |
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unilateral and associated with good vision in chronically diabetic patients. It has been described as |
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the microangiopathy of DR manifesting on the optic nerve head.11 No association with age was |
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reported in two studies.11,12 |
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It is important to be able to differentiate this entity from the more noxious pathologies like |
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papilledema, malignant hypertension and non-arteritic anterior ischemic optic neuropathy (NA- |
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AION) (Figures 3-3A to F). While the former two are essentially bilateral, the latter is usually |
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unilateral. Papilledema may be confirmed by neuroimaging and a lumbar puncture, while malignant |
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hypertension by a measurement of the blood pressure. NA-AION is distinguished from DP by the |
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more severe visual loss, field defects, moderate to marked afferent pupillary defects and poorer |
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visual outcome. Neovascularization of the disc can be made out by the radial arrangement of the |
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new vessels and their intense leak on angiography (Figures 3-3G and H). |
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DIABETIC TRACTIONAL PAPILLOPATHY |
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Vitreous traction confined to the optic nerve head resulting in elevation of the disc tissue was |
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demonstrated first by Kroll et al.13 The visual reduction in these cases was explained on the basis of |
Textbook of Vitreoretinal Diseases and Surgery
FIGURES 3-3A TO H: (A) Fundus photograph of an eye with diabetic papillopathy with significant edema of the disc.
(B) Fluorescein angiogram of the same eye showing mild leakage of the disc. (C) Fundus photograph showing an eye with malignant hypertension induced disc edema, shallow peripapillary and macular detachment with hard exudates in the form of a macular fan. (D) Fundus photograph of an eye with the pallid disc edema of anterior ishcemic optic neuropathy. (E, F) Fundus photograph of the right and left eye respectively of a patient with the characteristic bilateral disc edema of papilledema. (G) Fundus photograph of an eye with massive neovascularisation of the disc
34 secondary to proliferative diabetic retinopathy. (H) Fluorescein angiogram of the same eye demonstrating the intense leak of the neovascular complex
Atypical Manifestations of Diabetic Retinopathy
the mechanical stretch of the axons and compromised blood flow. Vitrectomy was noted to improve both vision and visually evoked potentials.
ATYPICAL COTTON-WOOL SPOTS
Giant cotton-wool spots ranging in size from 2-4 disc diameters have been described.14 These were reported to occur after a stenosis or total obstruction of a first order arteriole at the site of its branching from the parent artery. There appeared to be an attempt to maintain circulation by the surrounding arterioles and venules with the venules displaying a reversal of blood flow. The cotton wool spots were observed to be flanked by arteriovenous communications.
FOVEAL NEOVASCULARIZATION IN DIABETIC RETINOPATHY
Neovascularization within the foveal ring is a rare occurrence that was reported initially by Finkelstein et al and later by Joondeph et al.15,16 These new vessels were noted to be nonprogressive, had good vision and associated with long standing diabetes (Figure 3-4). Midperipheral areas of neovascularization were noted additionally in most cases. This phenomenon was explained on the basis of there invariably always being some amount of capillary nonperfusion in the posterior pole.
FIGURE 3-4: Fluorescein angiogram revealing foveal neovascularization along with neovascularization in the mid-periphery in a case of proliferative diabetic retinopathy
SPONTANEOUS REGRESSION OF PROLIFERATIVE DIABETIC RETINOPATHY |
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Spontaneous regression of retinal neovascularization was first reported in three pregnant women |
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with type 1 diabetes, none of whom had a significant reduction in glycemic levels.17 Reperfusion of |
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the ischemic areas was noted on angiography. Similar spontaneous regression of new vessels has |
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been documented with amelioration of blood sugar levels and at the end of a pregnancy.17,18 Given |
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the extreme rarity of this scenario, panretinal photocoagulation remains the standard of care for |
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high-risk PDR. |
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Textbook of Vitreoretinal Diseases and Surgery
Systemic Diseases Affecting Diabetic Retinopathy
CAROTID OCCLUSIVE DISEASE
Diabetic retinopathy has for long known to be affected by carotid occlusive disease. Gay et al19 and later Moss et al20, in the Wisconsin Epidemiological Study of Diabetic Retinopathy, proposed that it may exert a protective influence on the course of DR.
LIPEMIC RETINOPATHY
A milder form of lipemia retinalis, “lipemic diabetic retinopathy” occurs when serum lipids, especially triglycerides, increases in a diabetic patient. The posterior pole is characterized by excessive deposition of hard exudates. Reduction of such extensive deposition of exudates may be achieved with statins, which may however not translate into visual improvement.21,22
Ocular Diseases Affecting Diabetic Retinopathy
Moss et al20 and Dogru et al23 showed that myopia was protective against the progression of DR to PDR. Even in non-myopes with diabetes, eyes with retinopathy had shorter axial lengths than those without retinopathy.24 The mechanisms suggested have been reduced ocular blood flow, thinning of retina in the myopic eye improving oxygen diffusion, and better pressure dissemination by the arteriolar network.25,26
The severity and progression of DR is also mitigated by glaucoma, which may be related to the retarded metabolic activity secondary to the ganglion cell loss and reduced blood perfusion in glaucoma.27 Optic atrophy has also been shown to similarly retard DR progression.28 Total posterior vitreous detachment is also known to slow the progression of retinopathy.23 Patients with retinitis pigmentosa, owing to the reduction in photoreceptors, demonstrate a low rate of DR progression.29
Miscellaneous
Assymmetric DR, reported in about 5 to 10%, has been defined as PDR in one eye and nonproliferative DR or no retinopathy in the fellow eye for a period of at least 2 years.30,23 The pathologies mentioned in the section above retard DR progression while cataract surgery and vein occlusions tend to faster progression.
Conclusion
The identification of the rarer and unusual presentations of diabetic retinopathy are important, given the rising incidence and prevalence of this disease world over. Uncommon and atypical presentations of the disease may, in addition, pave the way for newer treatment modalities for this malady.
References
1. BeaumontP,HollowsFC.Classificationofdiabeticretinopathy,withtherapeuticImplications.Lancet1972;1:419-24. 36 2. Favard C, Guyot-Argenton C, Assouline M, Marie-Lescure C, Pouliquen YJ. Full panretinal photocoagulation and
early vitrectomy improve prognosis of florid diabetic retinopathy. Ophthalmology 1996; 103: 561–74.
Atypical Manifestations of Diabetic Retinopathy
3.Lattanzio R, Brancato R, Bandello FM, Azzolini C, Malegori A, Maestranzi G. Florid diabetic retinopathy (FDR): a long-term follow-up study. Graefes Arch Clin Exp Ophthalmol 2001; 239:182–7.
4.Davis MD, Blodi BA. Proliferative diabetic retinopathy. In Retina. Edited by Ryan SJ. St. Louis: Mosby; 2001:1309– 49.
5.Shimizu K, Kobayashi Y, Muraoka K. Midperipheral fundus involvement in diabetic retinopathy. Ophthalmology 1981; 88: 601–12.
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17.Bandello F, Gass JD, Lattanzio R, Brancato R. Spontaneous regression of neovascualrization at the disk and elsewhere in diabetic retinopathy. Am J Ophthalmol 1996; 122: 494–501.
18.Rosenlund EF, Hakkens K, Brinchmann-Hansen O, Dahl-Jørgensen K, Hanssen KF et al. Transient proliferative diabetic retinopathy during intensified insulin treatment. Am J Ophthalmol 1988; 105: 618–25.
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20.Moss SE, Klein R, Klein BEK. Ocular factors in the incidence and progression of diabetic retinopathy. Ophthalmology 1994; 101: 77–83.
21.Jain SS, Thomas S, Motwane SA, Seth A. Lipemia retinalis in a case of juvenile diabetic ketoacidosis. Indian J Ophthalmol 1999; 47: 192–93.
22.Chew EY, Klein ML, Ferris FL 3rd, Remaley NA, Murphy RP, Chantry K et al. Association of elevated serum lipid levels with retinal hard exudates in diabetic retinopathy. Early Treatment Diabetic Retinopathy Study (ETDRS) Report 22. Arch Ophthalmol 1996; 114: 1079–84.
23.Dogru M, Inoue M, Nakamura M, Yamamoto M. Modifying factors related to asymmetric diabetic retinopathy. Eye 1998; 12: 929–33.
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19:401–04.
25.Baker RS, Rand LI, Krolewski AS, Maki T, Warram JH, Aiello LM. Influence of HLA-DR phenotype and myopia on the risk of nonproliferative and proliferative diabetic retinopathy. Am J Ophthalmol 1986; 102: 693–700.
26.Quigley M, Cohen S. A new pressure attenuation index to evaluate retinal circulation. A link to protective factors in diabetic retinopathy. Arch Ophthalmol 1999; 117: 84–89.
27.Frank R. Etiologic mechanisms in diabetic retinopathy. In Retina, edn 3. Edited by Ryan SJ. St. Louis: Mosby; 2001:1264–94.
28.Dellaporta A. The negative coincidence of retinitis pigmentosa and proliferative diabetic retinopathy [letter]. Am J Ophthalmol 1984; 98: 524.
29.Arden GB: The absence of diabetic retinopathy in patients with retinitis pigmentosa: implications for pathophysiology and possible treatment. Br J Ophthalmol 2001, 85: 366–70.
30.Duker JS, Brown GC, Bosley TM, Colt CA, Reber R. Asymmetric proliferative diabetic retinopathy and carotid artery disease. Ophthalmology 1990, 97: 869–74.
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