Ocufolin^®

The Effects of Vitamin Supplementation Containing L-Methylfolate (Ocufolin^® forte) on Retinal Venous Pressure and Homocysteine Plasma Levels in Patients with Glaucoma

Thibaut Devogelaere,¹ Andreas Schötzau,²

Purpose: To report our observations of the effects of Ocufolin^® forte on elevated retinal venous pressure (RVP) and elevated serum homocysteine (Hcy) in patients with glaucoma and/or ocular vascular diseases.
Methods: A total of 26 patients with glaucoma and/or ocular vascular diseases in at least one eye, abnormal steady-state pattern electroretinography, RVP measured using an ophthalmodynamometer at least 15 mmHg higher than intra-ocular pressure (IOP), fasting serum Hcy level >12 μmol/l and stable and well-controlled IOP (with or without IOP-lowering treatment) received supplementation with Ocufolin^® forte for 3 months.
Results: As additional treatment was needed in 2 patients their results were excluded from analysis. In the remaining 24 patients, 42 eyes of 21 patients qualified for RVP analysis. Mean IOP remained stable (p=0.15) during the study, but mean RVP dropped by 8.8 mmHg (p<0.001), from 28.1±11.7 mmHg at pre-supplementation to 19.3±7.4 mmHg at 3 months. In 22 of the 24 patients, serum Hcy was analyzed again between 3 days and almost 41 weeks after cessation of supplementation. Serum Hcy levels dropped from 15.8±2.8 μmol/l before to 12.51±2.90 μmol/l after supplementation (p<0.001).
Conclusions: In this pilot study, Ocufolin^® forte had a clinically relevant and statistically significant RVP lowering effect and led to a clinically relevant and statistically significant Hcy decrease, offering a new treatment modality for eye diseases with increased RVP, such as glaucoma.

Devogelaere Schötzau_healthbook TIMES Schw Aerztej_3(2021)54_L-Methylfolate formulation Retinal Venous pressure Homocysteine Glaucoma

https://schw-aerztej.healthbooktimes.org/article/30108-the-effects-of-vitamin-supplementation-containing-l-methylfolate-ocufolin-forte-on-retinal-venous-pressure-and-homocysteine-plasma-levels-in-patien

Measuring and Treating Retinal Venous Pressure: Efforts and Benefits

Expert Opinion by Josef Flammer

Dr. Thibaut Devogelaere studied the effect of Ocufolin^® forte on retinal venous pressure (RVP) in glaucoma patients. This seemingly unspectacular information is, in our opinion, a big step forward for many patients, especially glaucoma patients. Therefore, it has prompted us to write some general thoughts on the measurement and treatment of elevated RVP in glaucoma.

Editorial Times Healthbook November 2021

Can we improve ocular blood flow and protect the eye?

Expert Opinion by A. David Smith

Maintenance of a good blood flow through the eye is crucial and impairment or dysregulation of blood flow is a likely cause of several diseases of the eye. In particular, raised retinal venous pressure (RVP) has many adverse effects. The blood vessels in the retina are unusual in that they are not innervated by autonomic nerves and the control of blood flow is largely mediated by local release of vasoactive substances, mainly from the vascular endothelium. Hence, impaired blood flow is often the consequence of the impaired function of the vascular endothelium (vascular endotheliopathy), which can be caused by hypertension, diabetes, oxidative stress and raised plasma homocysteine or by primary vascular dysregulation (the Flammer syndrome).

Editorial Times Healthbook November 2021

A pilot study to assess the effect of a three-month vitamin supplementation containing L-methylfolate on systemic homocysteine plasma concentrations and retinal blood flow in patients with diabetes

Doreen Schmidl,¹ Kinga Howorka,² Stephan Szegedi,¹ Kristina Stjepanek,^1,3 Stefan Puchner,^1,2 Ahmed Bata,¹ Ulrike Scheschy,¹ Gerold Aschinger,² René M. Werkmeister,² Leopold Schmetterer,^{1,2,4,5,6,7,8} Gerhard Garhofer¹

Improved Retinal Microcirculation in Mild Diabetic Retinopathy Patients Carrying MTHFR Polymorphisms Who Received the Medical Food, Ocufolin^®

Zhiping Liu ^1,2, Hong Jiang^2,3, Justin H Townsend ², Jianhua Wang²

¹Ophthalmic Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China;
²Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA; ³Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA

Purpose: To evaluate the effects of Ocufolin^® on retinal microcirculation in patients with mild diabetic retinopathy carrying MTHFR polymorphisms.
Methods: In a prospective, case-controlled study, eight patients with mild diabetic retinopathy and MTHFR polymorphisms and 15 normal controls (NC) were recruited. MTHFR polymorphisms were subtyped as normal, C677T, or A1298C. Best-corrected visual acuity (BCVA) was evaluated. Retinal blood flow velocity (BFV) was measured using Retinal Function Imager. Retinal tissue perfusion (RTP, blood flow rate per inner retinal volume) was calculated within a 2.5 mm diameter circle centered on the fovea. The eight retinopathy patients received Ocufolin^® for 6 months, and their imaging was performed at baseline, 4 months, and 6 months. The NC group was imaged once.
Results: BCVA and vascular indices of DR + PM patients at baseline were below those of NC and improved after Ocufolin^® administration. Compared to baseline, DR + PM patients had significantly improved BCVA during the follow-up period (P < 0.05). RTP and arteriolar BFV were significantly increased at 6 months (P < 0.05), approaching NC.
Conclusion: Ocufolin^® may be effective in improving both visual acuity and retinal microcirculation in patients with DR + PM. Further studies with increasing sample size, and longer duration, including cases with severe DR, are needed.

https://www.dovepress.com/improved-retinal-microcirculation-in-mild-diabetic-retinopathy-patient-peer-reviewed-fulltext-article-OPTH 

Effects of Ocufolin^® on retinal microvasculature in patients with mild non-proliferative diabetic retinopathy carrying polymorphisms of the MTHFR gene

Zhiping Liu, Hong Jiang, Justin H Townsend, Jianhua Wang

Introduction: To evaluate effects of Ocufolin^® on retinal microvasculature in mild non-proliferative diabetic retinopathy patients who carried methylenetetrahydrofolate reductase (MTHFR) polymorphisms (DR +MTHFRP).

Research design and methods: This is a prospective cohort study. Eight DR +MTHFRP (administrated Ocufolin^® for 6 months) and 15 normal controls (NCs) were recruited. MTHFR polymorphisms were subtyped as normal, C677T, or A1298C. Best-corrected visual acuity (BCVA) was evaluated. Retinal vessel density (VD) and microstructure were evaluated by optical coherence tomography angiography.

Results: BCVA and vascular indices of DR +MTHFRP at baseline were worse than those of NC and improved. Compared with baseline, DR +MTHFRP had significantly improved BCVA during follow-up period (p<0.05). VD of superficial vascular plexus was increased at 4 months (p=0.012), while VD of retinal vascular network did not change (p>0.05). Carriers of A1298C and C677T showed statistically significant increase in VD at all layers by 6 months, while carriers of C677T alone showed no significant change and carriers of A1298C alone showed decreased density from 4 months to 6 months. Microstructure did not change during the follow-up period.

Conclusion: A 6-month intake of Ocufolin is capable of reversing structural changes of microangiopathy in mild non-proliferative DR +MTHFRP. This suggests a novel way to address these impairments prior to catastrophic vision loss.

https://drc.bmj.com/content/9/1/e002327

Nutritional and medical food therapies for diabetic retinopathy

Ce Shi, Peng Wang, Shriya Airen, Craig Brown, Zhiping Liu, Justin H. Townsend, Jianhua Wang & Hong Jiang

Abstract: Diabetic retinopathy (DR) is a form of microangiopathy. Reducing oxidative stress in the mitochondria and cell membranes decreases ischemic injury and end-organ damage to the retina. New approaches are needed, which reduce the risk and improve the outcomes of DR while complementing current therapeutic approaches. Homocysteine (Hcy) elevation and oxidative stress are potential therapeutic targets in DR.

Common genetic polymorphisms such as those of methylenetetrahydrofolate reductase (MTHFR), increase Hcy and DR risk and severity. Patients with DR have high incidences of deficiencies of crucial vitamins, minerals, and related compounds, which also lead to elevation of Hcy and oxidative stress. Addressing the effects of the MTHFR polymorphism and addressing comorbid deficiencies and insufficiencies reduce the impact and severity of the disease. This approach provides safe and simple strategies that support conventional care and improve outcomes.

Suboptimal vitamin co-factor availability also impairs the release of neurotrophic and neuroprotective growth factors. Collectively, this accounts for variability in presentation and response of DR to conventional therapy. Fortunately, there are straightforward recommendations for addressing these issues and supporting traditional treatment plans.

We have reviewed the literature for nutritional interventions that support conventional therapies to reduce disease risk and severity. Optimal combinations of vitamins B1, B2, B6, L-methylfolate, methylcobalamin (B12), C, D, natural vitamin E complex, lutein, zeaxanthin, alpha-lipoic acid, and n-acetylcysteine are identified for protecting the retina and choroid. Certain medical foods have been successfully used as therapy for retinopathy. Recommendations based on this review and our clinical experience are developed for clinicians to use to support conventional therapy for DR.

DR from both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) have similar retinal findings and responses to nutritional therapies. 

https://doi.org/10.1186/s40662-020-00199-y

Improving diabetic and hypertensive retinopathy with a medical food containing L-methylfolate: a preliminary report

Jianhua Wang, Craig Brown, Ce Shi, Justin Townsend, Giovana Rosa Gameiro, Peng Wang & Hong Jiang

Background: Homocysteine and vitamin D may play a role in the development of diabetic and hypertensive retinopathy in patients with diabetes mellitus (DM) and hypertension. Supplementing food with L-methylfolate and vitamin D theoretically may improve diabetic and hypertensive retinopathy, however, the outcome of these nutritional approaches has not been fully examined. A retrospective case review was done of cases of retinopathy reversal in patients on Ocufolin™ and a similar nonprescription multivitamin, Eyefolate™. In this study, they were administered L-methylfolate (2.7 mg and 3.0 mg, respectively) and vitamin D3 (4500 IU each). These dosages are significantly above the RDA but well below levels associated with toxicity. 

Case presentation: Seven patients had nonproliferative diabetic retinopathy (NPDR) and some of them had hypertension. One patient had only hypertensive retinopathy. All patients were instructed to take Ocufolin^® medical food as a food supplement. Baseline genetic testing for MTHFR polymorphisms was conducted. Fundus photography was used to document the fundus condition of the enrolled eyes in 8 NPDR patients at the initial and follow-up visits. Microaneurysms (MA) and exudates were observed to be improved in some trial patients. All subjects had one or more MTHFR polymorphisms. All had diabetic retinopathy, hypertensive retinopathy, or both. MAs were resolved, and exudates were decreased in 8/8 cases after taking the medical food. Retinal edema was found in 2/8 cases and improved or resolved in both cases after taking the medical food or the supplement. The best corrected visual activity was stable or improved in 8/8 cases.

Conclusion: We report a series of diabetic and hypertensive retinopathy cases with MTHFR polymorphisms and the improvement of retinal microvasculature (mainly MAs) in serial fundus photography after taking a medical food or supplement containing L-methylfolate and vitamin D. It appears that the use of nutritional supplements and medical foods containing L-methylfolate and vitamin D may be effective in facilitating the improvement of diabetic and hypertensive retinopathy.

https://doi.org/10.1186/s40662-019-0147-0