Progress in diagnosis and treatment of diabetic retinopathy with leukemia_Chinese Journal of Ocular Fundus Diseases

Authors：

Ju Yuqiao ,  Huang Xin

Department of Ophthalmology, The Eye-ENT Hospital of Fudan University, Shanghai 200031, China;

Corresponding?author：

Huang Xin, Email: fd2017huangxin@163.com

Keywords：

Diabetic retinopathy; Leukemia; Review

DOI：

10.3760/cma.j.cn511434-20201221-00626

Video：

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Combined with leukemia is a risk factor for aggravating diabetic retinopathy. A combination of diabetic retinopathy and leukemia can be expected to have a rapid progression and patients often visit the department of ophthalmology first. In addition to the typical manifestations of diabetic retinopathy such as retinal venous tortuous dilation, microaneurysm, retinal hemorrhage and exudation, patients may also be associated with leukemic retinopathy. Areas of extensive capillary non-perfusion and neovascularization may appear in the early stage of mild microangiopathy. Moreover, severe complications such as vitreous hemorrhage, neovascular membranes and traction retinal detachment appear earlier, which may be a prognostic indicator for poor vision. The causes of leukemia aggravating diabetic retinopathy include retinal ischemia due to hyperviscosity, anemia and thrombocytopenia, direct infiltration of tumor cells, chemotherapy and radiotherapy, high level of vascular endothelial growth factor. In clinic, rapidly progressing diabetic retinopathy should alert the ophthalmologist to the underlying hematological disorder. Patients with both diabetes and leukemia need to be screened much earlier and followed up at shorter intervals. Early detection and aggressive management may help preserve visual acuity in such cases.

Citation： Ju Yuqiao, Huang Xin. Progress in diagnosis and treatment of diabetic retinopathy with leukemia. Chinese Journal of Ocular Fundus Diseases, 2021, 37(1): 64-67. doi: 10.3760/cma.j.cn511434-20201221-00626 Copy

1.	Cheung N, Mitchell P, Wong TY. Diabetic retinopathy[J]. Lancet, 2010, 376(9735): 124-136. DOI: 10.1016/S0140-6736(09)62124-3.
2.	Juliusson G, Hough R. Leukemia[J]. Prog Tumor Res, 2016, 43: 87-100. DOI: 10.1159/000447076.
3.	Apperley JF. Chronic myeloid leukaemia[J]. Lancet, 2015, 385(9976): 1447-1459. DOI: 10.1016/S0140-6736(13)62120-0.
4.	Reddy SC, Jackson N, Menon BS. Ocular involvement in leukemia--a study of 288 cases[J]. Ophthalmologica, 2003, 217(6): 441-445. DOI: 10.1159/000073077.
5.	Guyer DR, Schachat AP, Vitale S, et al. Leukemic retinopathy. relationship between fundus lesions and hematologic parameters at diagnosis[J]. Ophthalmology, 1989, 96(6): 860-864. DOI: 10.1016/s0161-6420(89)32809-0.
6.	Rosenthal AR. Ocular manifestations of leukemia: a review[J]. Ophthalmology, 1983, 90(8): 899-905. DOI: 10.1016/s0161-6420(83)80013-x.
7.	Nobacht S, Vandoninck KF, Deutman AF, et al. Peripheral retinal nonperfusion associated with chronic myeloid leukemia[J]. Am J Ophthalmol, 2003, 135(3): 404-406. DOI: 10.1016/s0002-9394(02)01956-6.
8.	Frank RN, Ryan SJ Jr. Peripheral retinal neovascularization with chronic myelogenous leukemia[J]. Arch Ophthalmol, 1972, 87(5): 585-589. DOI: 10.1001/archopht.1972.01000020587017.
9.	Hoerauf H, Bopp S, Laqua H. Proliferative retinopathy in chronic myeloid leukemia[J]. Klin Monbl Augenheilkd, 1994, 205(4): 226-130. DOI: 10.1055/s-2008-1045520.
10.	Hasanreisoglu B, Or M, Atmaca LS, et al. Pars plana vitrectomy in chronic myelogenous leukemia with vitreous hemorrhage[J]. Jpn J Ophthalmol, 1988, 32(3): 304-309.
11.	Mandava N, Costakos D, Bartlett HM. Chronic myelogenous leukemia manifested as bilateral proliferative retinopathy[J]. Arch Ophthalmol, 2005, 123(4): 576-577. DOI: 10.1001/archopht.123.4.576.
12.	Yoshid F, Okamoto N, Hosotani Y, et al. A case of acute lymphoblastic leukemia with variable appearance[J]. Nippon Ganka Gakkai Zasshi, 2010, 114(1): 28-33.
13.	Chawla R, Kumar S, Kumawat D, et al. Chronic myeloid leukaemia accelerates proliferative retinopathy in patients with co-existent diabetes: a risk factor not to be ignored[J/OL]. Eur J Ophthalmol, 2019, 2019: 1120672119875341[2019-09-12].https://pubmed.ncbi.nlm.nih.gov/31514533/. DOI: 10.1177/1120672119875341.
14.	居鈺喬, 楊茜, 常青, 等. 合并慢性粒細胞白血病的增生型糖尿病視網膜病變患者五例[J]. 中華眼底病雜志, 2021, 37(1): ……. DOI: 10.3760/cma.j.cn511434-20201223-00632.Ju YQ, Yang Q, Chang Q, et al. Clinical observations of proliferative diabetic retinopathy with chronic myeloid leukemia of five cases[J]. Chin J Ocul Fundus Dis, 2021, 37(1): ……. DOI: 10.3760/cma.j.cn511434-20201223-00632.
15.	Figueiredo LM, Rothwell RT, Meira D, et al. Chronic myeloid leukemia diagnosed in a patient with uncontrolled proliferative diabetic retinopathy[J]. Retin Cases Brief Rep, 2015, 9(3): 210-213. DOI: 10.1097/ICB.0000000000000140.
16.	Tsiamita O, Siempis T, Varikkara M. Reduced vision in a diabetic patient due to incidental leukaemic retinopathy[J]. Clin Exp Optom, 2019, 102(1): 91-93. DOI: 10.1111/cxo.12808.
17.	Shahid SM, Waqar S, Ling R. Sudden apparent worsening of diabetic retinopathy leading to a diagnosis of chronic myeloid leukaemia[J/OL]. Br J Hosp Med (Lond), 2013, 74(9): 533[2013-11-13]. https://pubmed.ncbi.nlm.nih.gov/24022560/. DOI: 10.12968/hmed.2013.74.9.533.
18.	Rocke JR, Clark JB, Campbell PJ, et al. Florid Neovascularization of the retina in a diabetic patient undergoing induction and consolidation therapy for acute promyelocytic leukemia[J]. Retin Cases Brief Rep, 2019, 13(2): 189-193. DOI: 10.1097/ICB.0000000000000560.
19.	Roop P, Angmo D, Kamble N, et al. Uncontrolled neovascular glaucoma-an alarming manifestation of chronic myeloid leukemia on imatinib therapy-a case report and review of literature[J]. Indian J Ophthalmol, 2019, 67(2): 285-287. DOI: 10.4103/ijo.IJO_1288_18.
20.	Melberg NS, Grand MG, Rup D. The impact of acute lymphocytic leukemia on diabetic retinopathy[J]. J Pediatr Hematol Oncol, 1995, 17(1): 81-84. DOI: 10.1097/00043426-199502000-00015.
21.	Holt JM, Gordon-Smith EC. Retinal abnormalities in diseases of the blood[J]. Br J Ophthalmol, 1969, 53(3): 145-160. DOI: 10.1136/bjo.53.3.145.
22.	Viswanath K, McGavin DD. Diabetic retinopathy: clinical findings and management[J]. Community Eye Health, 2003, 16(46): 21-24.
23.	Luxenberg MN, Mausolf FA. Retinal circulation in the hyperviscosity syndrome[J]. Am J Ophthalmol, 1970, 70(4): 588-598. DOI: 10.1016/0002-9394(70)90894-9.
24.	Merin S, Freund M. Retinopathy in severe anemia[J]. Am J Ophthalmol, 1968, 66(6): 1102-1106. DOI: 10.1016/0002-9394(68)90818-0.
25.	Kincaid MC, Green WR. Ocular and orbital involvement in leukemia[J]. Surv Ophthalmol, 1983, 27(4): 211-232. DOI: 10.1016/0039-6257(83)90123-6.
26.	Malek R, Davis SN. Tyrosine kinase inhibitors under investigation for the treatment of type Ⅱ diabetes[J]. Expert Opin Investig Drugs, 2016, 25(3): 287-296. DOI: 10.1517/13543784.2016.1142531.
27.	Martino B, Mammi C, Labate C, et al. Genetic risk of prediabetes and diabetes development in chronic myeloid leukemia patients treated with nilotinib[J]. Exp Hematol, 2017, 55: 71-75. DOI: 10.1016/j.exphem.2017.07.007.
28.	Prada PO, Saad MJ. Tyrosine kinase inhibitors as novel drugs for the treatment of diabetes[J]. Expert Opin Investig Drugs, 2013, 22(6): 751-763. DOI: 10.1517/13543784.2013.802768.
29.	Porges Y, Blumen S, Fireman Z, et al. Cyclosporine-induced optic neuropathy, ophthalmoplegia, and nystagmus in a patient with Crohn disease[J]. Am J Ophthalmol, 1998, 126(4): 607-609. DOI: 10.1016/s0002-9394(98)00137-8.
30.	Zamber RW, Kinyoun JL. Radiation retinopathy[J]. West J Med, 1992, 157(5): 530-533.
31.	Sillaber C, Mayerhofer M, Aichberger KJ, et al. Expression of angiogenic factors in chronic myeloid leukaemia: role of the bcr/abl oncogene, biochemical mechanisms, and potential clinical implications[J]. Eur J Clin Invest, 2004, 34 Suppl 2: S2-11. DOI: 10.1111/j.0960-135X.2004.01365.x.
32.	Schmid S, Lang-Muritano M, Meier U, et al. Transient severe non-proliferative retinopathy in an adolescent with type 1 diabetes and chronic myeloid leukemia[J]. Pediatr Diabetes, 2013, 14(3): 227-229. DOI: 10.1111/j.1399-5448.2012.00901.x.
33.	Bhisitkul RB. Vascular endothelial growth factor biology: clinical implications for ocular treatments[J]. Br J Ophthalmol, 2006, 90(12): 1542-1547. DOI: 10.1136/bjo.2006.098426.

1. Cheung N, Mitchell P, Wong TY. Diabetic retinopathy[J]. Lancet, 2010, 376(9735): 124-136. DOI: 10.1016/S0140-6736(09)62124-3.
2. Juliusson G, Hough R. Leukemia[J]. Prog Tumor Res, 2016, 43: 87-100. DOI: 10.1159/000447076.
3. Apperley JF. Chronic myeloid leukaemia[J]. Lancet, 2015, 385(9976): 1447-1459. DOI: 10.1016/S0140-6736(13)62120-0.
4. Reddy SC, Jackson N, Menon BS. Ocular involvement in leukemia--a study of 288 cases[J]. Ophthalmologica, 2003, 217(6): 441-445. DOI: 10.1159/000073077.
5. Guyer DR, Schachat AP, Vitale S, et al. Leukemic retinopathy. relationship between fundus lesions and hematologic parameters at diagnosis[J]. Ophthalmology, 1989, 96(6): 860-864. DOI: 10.1016/s0161-6420(89)32809-0.
6. Rosenthal AR. Ocular manifestations of leukemia: a review[J]. Ophthalmology, 1983, 90(8): 899-905. DOI: 10.1016/s0161-6420(83)80013-x.
7. Nobacht S, Vandoninck KF, Deutman AF, et al. Peripheral retinal nonperfusion associated with chronic myeloid leukemia[J]. Am J Ophthalmol, 2003, 135(3): 404-406. DOI: 10.1016/s0002-9394(02)01956-6.
8. Frank RN, Ryan SJ Jr. Peripheral retinal neovascularization with chronic myelogenous leukemia[J]. Arch Ophthalmol, 1972, 87(5): 585-589. DOI: 10.1001/archopht.1972.01000020587017.
9. Hoerauf H, Bopp S, Laqua H. Proliferative retinopathy in chronic myeloid leukemia[J]. Klin Monbl Augenheilkd, 1994, 205(4): 226-130. DOI: 10.1055/s-2008-1045520.
10. Hasanreisoglu B, Or M, Atmaca LS, et al. Pars plana vitrectomy in chronic myelogenous leukemia with vitreous hemorrhage[J]. Jpn J Ophthalmol, 1988, 32(3): 304-309.
11. Mandava N, Costakos D, Bartlett HM. Chronic myelogenous leukemia manifested as bilateral proliferative retinopathy[J]. Arch Ophthalmol, 2005, 123(4): 576-577. DOI: 10.1001/archopht.123.4.576.
12. Yoshid F, Okamoto N, Hosotani Y, et al. A case of acute lymphoblastic leukemia with variable appearance[J]. Nippon Ganka Gakkai Zasshi, 2010, 114(1): 28-33.
13. Chawla R, Kumar S, Kumawat D, et al. Chronic myeloid leukaemia accelerates proliferative retinopathy in patients with co-existent diabetes: a risk factor not to be ignored[J/OL]. Eur J Ophthalmol, 2019, 2019: 1120672119875341[2019-09-12].https://pubmed.ncbi.nlm.nih.gov/31514533/. DOI: 10.1177/1120672119875341.
14. 居鈺喬, 楊茜, 常青, 等. 合并慢性粒細胞白血病的增生型糖尿病視網膜病變患者五例[J]. 中華眼底病雜志, 2021, 37(1): ……. DOI: 10.3760/cma.j.cn511434-20201223-00632.Ju YQ, Yang Q, Chang Q, et al. Clinical observations of proliferative diabetic retinopathy with chronic myeloid leukemia of five cases[J]. Chin J Ocul Fundus Dis, 2021, 37(1): ……. DOI: 10.3760/cma.j.cn511434-20201223-00632.
15. Figueiredo LM, Rothwell RT, Meira D, et al. Chronic myeloid leukemia diagnosed in a patient with uncontrolled proliferative diabetic retinopathy[J]. Retin Cases Brief Rep, 2015, 9(3): 210-213. DOI: 10.1097/ICB.0000000000000140.
16. Tsiamita O, Siempis T, Varikkara M. Reduced vision in a diabetic patient due to incidental leukaemic retinopathy[J]. Clin Exp Optom, 2019, 102(1): 91-93. DOI: 10.1111/cxo.12808.
17. Shahid SM, Waqar S, Ling R. Sudden apparent worsening of diabetic retinopathy leading to a diagnosis of chronic myeloid leukaemia[J/OL]. Br J Hosp Med (Lond), 2013, 74(9): 533[2013-11-13]. https://pubmed.ncbi.nlm.nih.gov/24022560/. DOI: 10.12968/hmed.2013.74.9.533.
18. Rocke JR, Clark JB, Campbell PJ, et al. Florid Neovascularization of the retina in a diabetic patient undergoing induction and consolidation therapy for acute promyelocytic leukemia[J]. Retin Cases Brief Rep, 2019, 13(2): 189-193. DOI: 10.1097/ICB.0000000000000560.
19. Roop P, Angmo D, Kamble N, et al. Uncontrolled neovascular glaucoma-an alarming manifestation of chronic myeloid leukemia on imatinib therapy-a case report and review of literature[J]. Indian J Ophthalmol, 2019, 67(2): 285-287. DOI: 10.4103/ijo.IJO_1288_18.
20. Melberg NS, Grand MG, Rup D. The impact of acute lymphocytic leukemia on diabetic retinopathy[J]. J Pediatr Hematol Oncol, 1995, 17(1): 81-84. DOI: 10.1097/00043426-199502000-00015.
21. Holt JM, Gordon-Smith EC. Retinal abnormalities in diseases of the blood[J]. Br J Ophthalmol, 1969, 53(3): 145-160. DOI: 10.1136/bjo.53.3.145.
22. Viswanath K, McGavin DD. Diabetic retinopathy: clinical findings and management[J]. Community Eye Health, 2003, 16(46): 21-24.
23. Luxenberg MN, Mausolf FA. Retinal circulation in the hyperviscosity syndrome[J]. Am J Ophthalmol, 1970, 70(4): 588-598. DOI: 10.1016/0002-9394(70)90894-9.
24. Merin S, Freund M. Retinopathy in severe anemia[J]. Am J Ophthalmol, 1968, 66(6): 1102-1106. DOI: 10.1016/0002-9394(68)90818-0.
25. Kincaid MC, Green WR. Ocular and orbital involvement in leukemia[J]. Surv Ophthalmol, 1983, 27(4): 211-232. DOI: 10.1016/0039-6257(83)90123-6.
26. Malek R, Davis SN. Tyrosine kinase inhibitors under investigation for the treatment of type Ⅱ diabetes[J]. Expert Opin Investig Drugs, 2016, 25(3): 287-296. DOI: 10.1517/13543784.2016.1142531.
27. Martino B, Mammi C, Labate C, et al. Genetic risk of prediabetes and diabetes development in chronic myeloid leukemia patients treated with nilotinib[J]. Exp Hematol, 2017, 55: 71-75. DOI: 10.1016/j.exphem.2017.07.007.
28. Prada PO, Saad MJ. Tyrosine kinase inhibitors as novel drugs for the treatment of diabetes[J]. Expert Opin Investig Drugs, 2013, 22(6): 751-763. DOI: 10.1517/13543784.2013.802768.
29. Porges Y, Blumen S, Fireman Z, et al. Cyclosporine-induced optic neuropathy, ophthalmoplegia, and nystagmus in a patient with Crohn disease[J]. Am J Ophthalmol, 1998, 126(4): 607-609. DOI: 10.1016/s0002-9394(98)00137-8.
30. Zamber RW, Kinyoun JL. Radiation retinopathy[J]. West J Med, 1992, 157(5): 530-533.
31. Sillaber C, Mayerhofer M, Aichberger KJ, et al. Expression of angiogenic factors in chronic myeloid leukaemia: role of the bcr/abl oncogene, biochemical mechanisms, and potential clinical implications[J]. Eur J Clin Invest, 2004, 34 Suppl 2: S2-11. DOI: 10.1111/j.0960-135X.2004.01365.x.
32. Schmid S, Lang-Muritano M, Meier U, et al. Transient severe non-proliferative retinopathy in an adolescent with type 1 diabetes and chronic myeloid leukemia[J]. Pediatr Diabetes, 2013, 14(3): 227-229. DOI: 10.1111/j.1399-5448.2012.00901.x.
33. Bhisitkul RB. Vascular endothelial growth factor biology: clinical implications for ocular treatments[J]. Br J Ophthalmol, 2006, 90(12): 1542-1547. DOI: 10.1136/bjo.2006.098426.

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