Impact of Intensive Insulin Therapy on Diabetic Retinopathy

Intensive insulin therapy may speed up the development of diabetic retinopathy, placing some patients at a higher risk for blindness. 

Diabetic retinopathy (DR) remains the leading cause of adult-onset blindness. As a result of prolonged hyperglycemia, retinal perfusion is decreased, blocking the retinal capillaries, and producing vision loss. Previous studies have a positive association between normalization of glycemic levels and reduced DR progression in type 1 and type 2 diabetes patients. However, clinical trials have shown a new phenomenon, “early worsening of diabetic retinopathy,” in select type 1 and type 2 diabetes patients. Risk factors include high baseline HbA1c, long duration of diabetes, and DR severity. 

Moreover, the patients in these studies had minimal to moderate non-proliferative DR or did not have DR at baseline. Currently used therapies in patients with DR are pan-retinal photocoagulation, pars plana vitrectomy, and silicone oil injection. There is little literature regarding the impact of intensive insulin therapy in patients with proliferative diabetic retinopathy at baseline. The report presented evaluates the case of a patient with high-risk proliferative diabetic retinopathy given intensive insulin therapy. 

A 58-year-old woman of Asian descent presented with a one-year history of progressive vision loss in her right eye. The patient had type 2 diabetes for 21 years with poor glycemic control, with an HbA1c of 11%. Her antihyperglycemic therapy consisted of oral agents, and she was recently placed on insulin therapy the previous year. Her best-corrected visual acuity (BCVA) was 20/40 in the left eye and hand motion in the right eye at baseline. She was diagnosed as having high-risk proliferative DR in both eyes. She underwent pars plana vitrectomy in the right eye in combination with pan-retinal photocoagulation and silicone oil injection. After the procedure, the BCVA in her right eye was 20/1000. The patient was discharged with visual improvements in her right eye.  

Two months later, the patient presented with worsened vision loss in the left eye. The BCVA increased in the right eye to 20/160 and decreased in the left eye to 20/1000. She reported insulin use over the past two months with six units of aspart before meals and sixteen units of insulin glargine at bedtime, reducing her HbA1c to 7.3%. She had previously been treated with focal laser photocoagulation, which did not improve the BCVA of the left eye. After being admitted again, she underwent pars plana vitrectomy in her left eye in combination with pan-retinal photocoagulation and silicone oil injection. After the operation, the BCVA in her left eye improved to 20/200 and one month later had increased to 20/160. Two months post-follow-up, the BCVA in both eyes remained 20/160.  

Although insulin therapy reduces the overall incidence of DR and other diabetic complications, studies have shown the effects of intensive insulin therapy on DR progression. Patients with more severe DR types have a higher risk of developing early worsening of DR. The patient, in this case, had proliferative DR and, upon rapid glycemic control, experienced worsening of DR in her left eye. In contrast, the patient’s right eye BCVA did not decline after insulin therapy because of the DR treatment she underwent. This relationship suggests the benefit of immediate surgery and laser therapy in patients requiring intensive insulin therapy with severe forms of DR. Furthermore, insulin analogs with high affinity for the insulin-like growth factor, such as glargine and aspart, may rapidly progress worsening of DR. Since the patient in this study received both insulin analogs, the therapy chosen may have contributed to the progression of DR. In contrast, insulin analogs with a lower affinity such as glulisine and detemir may not have the same effect on vision loss. Overall, the case report presented highlights a high-risk patient and the impact of intensive insulin therapy on DR development. 

Practice Pearls: 

• Early recognition and management of diabetic retinopathy may reduce intensive insulin therapy’s adverse effects on vision loss. 
• The severity of diabetic retinopathy at baseline affects the risk of rapid progression of vision loss.  
• Further evidence is needed to compare the effects of different insulin therapies on the worsening of diabetic retinopathy. 

Wang S, Liu D, Zhang X, Bi H. Rapid progression of high-risk proliferative diabetic retinopathy induced by insulin intensive therapy: A case report. Medicine (Baltimore). 2021;100(7):e24379.  

Henricsson M, Berntorp K, Fernlund P, Sundkvist G. Progression of retinopathy in insulin-treated type 2 diabetic patients. Diabetes Care. 2002.  

Lim SW, van Wijngaarden P, Harper CA, et al. Early worsening of diabetic retinopathy due to intensive glycaemic control. Clin Exp Ophthalmol2019;47:265–73 

Macrina Ghali, PharmD Candidate 2021, Florida A&M University, College of Pharmacy and Pharmaceutical Sciences