Clinical Evidence: Retinoaspis

Combined Intravitreal Ranibizumab And Oral Supplementation With Docosahexaenoic Acid And Antioxidants For Diabetic Macular Edema

Two-Year Randomized Single-Blind Controlled Trial Results

Maria Lafuente et al

Purpose: To assess the 2-year effectiveness of intravitreal ranibizumab combined with a dietary supplement rich in docosahexaenoic acid (DHA) plus antioxidants in 62 patients with diabetic macular edema.

Methods: In a randomized single-blind controlled study, 33 subjects (42 eyes) received intravitreal ranibizumab alone and 29 (34 eyes) combined with DHA (1,050 mg/day). Monthly ranibizumab (0.5 mg) was given for the first 4 months followed by on as-needed treatment.

Results: At 24 months, the difference between groups in the decrease of central subfield macular thickness was significant in favor of the DHA supplementation group (95% confidence interval of the difference 7.20–97.656; P = 0.024), although improvement in best-corrected visual acuity measured in the Early Treatment Diabetic Retinopathy Study letters did not reach statistical significance (95% confidence interval 5.4–11.2, P , 0.66). At 24 months, gains of .5 and .10 letters were significantly higher in the DHA supplementation group as compared with controls when the worse and better seeing eyes were considered but other differences at 12 months and 24 months were not found.

Conclusion: Intravitreal ranibizumab combined with DHA supplementation reduced central subfield macular thickness after 2 years of follow-up as compared with ranibizumab alone in patients with diabetic macular edema. This anatomical improvement was accompanied by a trend for an amelioration of vision.

Retina 2017 Jul;37(7):1277-1286. doi: 10.1097/IAE.0000000000001363.

Clinical Applications of Astaxanthin in the Treatment of Ocular Diseases: Emerging Insights

 Giuseppe Giannaccare et al

Abstract: Astaxanthin is a naturally occurring red carotenoid pigment belonging to the family of xanthophylls, and is typically found in marine environments, especially in microalgae and seafood such as salmonids, shrimps and lobsters. Due to its unique molecular structure, astaxanthin features some important biologic properties, mostly represented by strong antioxidant, anti-inflammatory and antiapoptotic activities. A growing body of evidence suggests that astaxanthin is efficacious in the prevention and treatment of several ocular diseases, ranging from the anterior to the posterior pole of the eye. Therefore, the present review aimed at providing a comprehensive evaluation of current clinical applications of astaxanthin in the management of ocular diseases. The efficacy of this carotenoid in the setting of retinal diseases, ocular surface disorders, uveitis, cataract and asthenopia is reported in numerous animal and human studies, which highlight its ability of modulating several metabolic pathways, subsequently restoring the cellular homeostatic balance. To maximize its multitarget therapeutic effects, further long-term clinical trials are warranted in order to define appropriate dosage, route of administration and exact composition of the final product.

Mar. Drugs 2020, 18, 239; doi:10.3390/md18050239

Dietary Marine ω-3 Fatty Acids and Incident Sight-Threatening Retinopathy in Middle-Aged and Older Individuals with Type 2 Diabetes Prospective Investigation From the PREDIMED Trial

Aleix Sala-Vila et al

IMPORTANCE: Diabetic retinopathy (DR) is a devastating complication of individuals with type2 diabetes mellitus. The retina is rich in long-chain ω-3 polyunsaturated fatty acids (LCω3PUFAs), which are substrate for oxylipins with anti-inflammatory and antiangiogenic properties. Experimental models support dietary LCω3PUFA protection against DR, but clinical data are lacking.

OBJECTIVE: To determine whether LCω3PUFA intake relates to a decreased incidence of sight-threatening DR in individuals with type 2 diabetes older than 55 years.

DESIGN, SETTING, AND PARTICIPANTS: In late 2015, we conceived a prospective study with in the randomized clinical trial Prevención con Dieta Mediterránea (PREDIMED), testing Mediterranean diets supplemented with extra virgin olive oil or nuts vs a control diet for primary cardiovascular prevention. The trial was conducted in primary health care centers in Spain. From 2003 to 2009, 3614 individuals aged 55 to 80 years with a previous diagnosis of type 2 diabetes were recruited. Full data were available for 3482 participants (48% men;mean age 67 years).

EXPOSURES Meeting the dietary LCω3PUFA recommendation of at least 500 mg/d for primary cardiovascular prevention, as assessed by a validated food-frequency questionnaire.

MAIN OUTCOMES AND MEASURES: The main outcome was incident DR requiring laser photo coagulation, vitrectomy, and/or antiangiogenic therapy confirmed by an external adjudication committee

RESULTS: Of the 3482 participants, 48% were men and the mean age was 67 years. A total of2611 participants (75%) met target LCω3PUFA recommendation. During a median follow-up of 6 years, we documented 69 new events. After adjusting for age, sex, intervention group, and lifestyle and clinical variables, participants meeting the LCω3PUFA recommendation at baseline (!500 mg/d) compared with those not fulfilling this recommendation (<500 mg/d) showed a 48% relatively reduced risk of incident sight-threatening DR, with a hazard ratio of0.52 (95% CI, 0.31-0.88;P= .001). This association was slightly stronger for yearly updated LCω3PUFA intake (relative risk, 0.48; 95% CI, 0.28-0.82;P= .007).

CONCLUSIONS AND RELEVANCE: In middle-aged and older individuals with type 2 diabetes, intake of at least 500 mg/d of dietary LCω3PUFA, easily achievable with 2 weekly servings of oily fish, is associated with a decreased risk of sight-threatening DR. Our results concur with findings from experimental models and the current model of DR pathogenesis.

TRIAL REGISTRATION: clinicaltrials.govIdentifier:http://www.controlled-trials.com/ISRCTN35739639

JAMA Ophthalmol. 2016;134(10):1142-1149. doi:10.1001/jamaophthalmol.2016.2906 Published online August 18, 2016.

Effect of vitamin B12 supplementation on retinal lesions in diabetic rats

S. Sreenivasa Reddy, Y. K. Prabhakar et al

Purpose: Diabetic retinopathy (DR) is the most common complication of diabetes involving microvasculature and neuronal alterations in the retina. Previously, we reported that vitamin B12 deficiency could be an independent risk factor for DR in humans. However, the effect of vitamin B12 supplementation in experimental DR is unknown. Thus, in this study, we investigated the impact of dietary supplementation of vitamin B12 on retinal changes in diabetic rats.

Methods: Diabetes was induced in 2-month-old Sprague-Dawley rats and maintained for 4 months. One group of diabetic rats were fed normal levels of vitamin B12, and one group double the quantity of vitamin B12 (50 µg/kg diet). Vitamin B12 and homocysteine levels in the plasma were analyzed with radioimmunoassay (RIA) and high-performance liquid chromatography (HPLC), respectively. At the end of 4 months of experimentation, the eyeballs were collected. Retinal changes were analyzed with hematoxylin and eosin (H&E) staining, immunoblotting, and immunofluorescence methods.

Results: Dietary supplementation of vitamin B12 had no effect on food intake, bodyweight, fasting blood glucose, and plasma homocysteine levels in the diabetic rats. However, vitamin B12 supplementation prevented loss of rhodopsin, and overexpression of VEGF, and completely prevented overexpression of HIF1α, GFAP, and endoplasmic reticulum (ER) stress markers (GRP78, ATF6α, XBP1, CHOP, and caspase 12) in the diabetic rat retina. Further, vitamin B12 ameliorated apoptosis in the retina as shown with terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and prevented retinal thinning.

Conclusions: Vitamin B12 supplementation of diabetic rats appeared to be beneficial by circumventing retinal hypoxia, VEGF overexpression, and ER stress-mediated cell death in the retina. The present study adds another potential therapeutic strategy of vitamin B12 in diabetes.

Molecular Vision 2020; 26:311-325 http://www.molvis.org/molvis/v26/311