Lawrence Ulanski

Observation of Human Retinal Remodeling in Octogenarians with a Resveratrol Based Nutritional Supplement

Purpose: Rare spontaneous remissions from age-related macular degeneration (AMD) suggest the human retina has large regenerative capacity, even in advanced age. We present examples of robust improvement of retinal structure and function using an OTC oral resveratrol (RV) based nutritional supplement called Longevinex® or L/RV (circa 2004, Resveratrol Partners, LLC, Las Vegas, NV, USA). RV, a polyphenolic phytoalexin caloric-restriction mimic, induces hormesis at low doses with widespread beneficial effects on systemic health. RV alone inhibits neovascularization in the murine retina. Thus far, published evidence includes L/RV mitigation of experimentally induced murine cardiovascular reperfusion injury, amelioration of human atherosclerosis serum biomarkers in a human Japanese randomized placebo controlled trial, modulation of micro RNA 20b and 539 that control hypoxia-inducing-factor (HIF-1) and vascular endothelial growth factor (VEGF) genes in the murine heart (RV inhibited micro RNA20b 189-fold, L/RV 1366-fold). Little is known about the effects of L/RV on human ocular pathology. Methods: Absent FDA IRB approval, but with permission from our Chief of Staff and medical center IRB, L/RV is reserved for AMD patients, on a case-by-case compassionate care basis. Patients include those who progress on AREDS II type supplements, refuse intra-vitreal anti-VEGF injections or fail to respond to Lucentis®, Avastin® or Eylea®. Patients are clinically followed traditionally as well as with multi-spectral retinal imaging, visual acuity, contrast sensitivity, cone glare recovery and macular visual fields. Three cases are presented. Results: Observed dramatic short-term anti-VEGF type effect including anatomic restoration of retinal structure with a suggestion of improvement in choroidal blood flow by near IR multispectral imaging. The visual function improvement mirrors the effect seen anatomically. The effect is bilateral with the added benefit of better RPE function. Effects have lasted for one year or longer when taken daily, at which point one patient required initiation of anti-VEGF agents. Unanticipated systemic benefits were observed. Conclusions: Preliminary observations support previous publications in animals and humans. Restoration of structure and visual function in octogenarians with daily oral consumption of L/RV is documented. Applications include failure on AREDS II supplements, refusing or failing conventional anti-VEGF therapy, adjunct therapy to improve RPE function, and compassionate use in medically underserved or economically depressed third-world countries.

Treating uveitis-associated hypotony with pars plana vitrectomy and silicone oil injection.

Purpose: The purpose of this study was to determine the effect on intraocular pressure (IOP) and visual acuity of treating uveitis-related hypotony in patients with vitrectomy and intravitreal silicone oil injection. Methods: Patients who underwent pars plana vitrectomy and silicone oil injection for uveitis-associated hypotony treatment were identified retrospectively. The primary outcome was maintaining an IOP of ≥5 mmHg. Visual acuity improvement was defined as an increase in ≥2 lines of acuity. Results: Twelve eyes of 10 patients were identified. Median preoperative IOP was 2 mmHg (range: 0–7 mmHg). Two of 12 eyes had an IOP of ≥5 mmHg at presentation. The number of eyes with an IOP of ≥5 mmHg was 7 of 12 eyes (58%) at 1 month, 4 of 12 eyes (33%) at 3 months, 6 of 12 eyes (50%) at 6 months, and 3 of 9 eyes (33%) at 1 year. Five of 12 eyes (42%) were reinjected between 1 and 3 times with silicone oil for recurring hypotony. Median presenting Snellen visual acuity was counting fingers (range: 20/125 to light perception). Seven of 9 eyes (78%) maintained their preoperative vision at 1 year. Conclusion: Intraocular pressure elevated modestly in most patients in this series. However, results were often transient, and some eyes required repeated silicone oil injections. Although silicone oil is reasonable to consider for the treatment and maintenance of IOP in patients with ocular hypotony secondary to uveitis, better treatments are needed.

Resveratrol Based Oral Nutritional Supplement Produces Long-Term Beneficial Effects on Structure and Visual Function in Human Patients

Background: Longevinex® (L/RV) is a low dose hormetic over-the-counter (OTC) oral resveratrol (RV) based matrix of red wine solids, vitamin D3 and inositol hexaphosphate (IP6) with established bioavailability, safety, and short-term efficacy against the earliest signs of human atherosclerosis, murine cardiac reperfusion injury, clinical retinal neovascularization, and stem cell survival. We previously reported our short-term findings for dry and wet age-related macular degeneration (AMD) patients. Today we report long term (two to three year) clinical efficacy. Methods: We treated three patients including a patient with an AMD treatment resistant variant (polypoidal retinal vasculature disease). We evaluated two clinical measures of ocular structure (fundus autofluorescent imaging and spectral domain optical coherence extended depth choroidal imaging) and qualitatively appraised changes in macular pigment volume. We further evaluated three clinical measures of visual function (Snellen visual acuity, contrast sensitivity, and glare recovery to a cone photo-stress stimulus). Results: We observed broad bilateral improvements in ocular structure and function over a long time period, opposite to what might be expected due to aging and the natural progression of the patient’s pathophysiology. No side effects were observed. Conclusions: These three cases demonstrate that application of epigenetics has long-term efficacy against AMD retinal disease, when the retinal specialist has exhausted other therapeutic modalities.

Aqueous and vitreous penetration of linezolid and levofloxacin after oral administration.

PURPOSE To evaluate the time course of drug concentrations achieved in aqueous (AQ), vitreous (V), and serum (S) compartments after oral administration of linezolid and levofloxacin. DESIGN Randomized, clinical trial. METHODS SETTINGS Clinical practice. PATIENT POPULATION Sixteen patients (16 eyes) undergoing vitrectomy who had not had a prior pars plana vitrectomy in the study eye were randomly assigned to one of 4 groups. INTERVENTION AQ, V, and S samples were obtained from all subjects after single concomitant doses of linezolid 600 mg and levofloxacin 750 mg between 1 and 12 h before the procedure: group A = 1-3 h; group B = 3-6 h; group C = 6-9 h; group D = 9-12 h. MAIN OUTCOME MEASURES AQ, V, and S concentrations of linezolid and levofloxacin. RESULTS Overall mean concentrations ± standard deviation (μg/mL) achieved by linezolid in AQ, V, and S compartments were 3.32 ± 2.06, 2.98 ± 1.87, and 7.91 ± 3.94, respectively. Overall mean concentrations ±standard deviation (μg/mL) achieved by levofloxacin in AQ, V, and S compartments were 2.19 ± 1.92, 1.95 ± 1.27, and 7.38 ± 3.47, respectively. CONCLUSIONS Single concomitant doses of linezolid and levofloxacin achieved AQ and V concentrations above the minimum inhibitory concentration for 90% of common ocular gram-positive and gram-negative pathogens up to 12 h after administration. The combination of linezolid and levofloxacin represents a viable option for the prophylaxis and management of endophthalmitis.

Pulmonary Metastasis Masquerading as Anterior Uveitis

in loss of BSCVA. As observed using OCT, we suggest here that the effect of Intacs in keratoconus is not on the cone’s apex but rather a more limited local flattening effect on the cornea surface above the segment. Because Intacs do not stretch the cone itself, it would explain why 1 inferior segment is better than 2 segments and why tighter channels should not make a difference. The local effect also explains why inserting a thicker superior segment is not as good as inserting a thicker inferior one near the steepest area of the cornea.

Restoration of Central Macular Pigment Dip with Dietary RR Zeaxanthin Supplementation in Patients with AMD

The central macula lutea (fovea) contains the highest density of cone photoreceptors, responsible for detailed and color vision in the central 2-3° of the visual field. AMD is the leading cause of permanent vision impairment in aging Western populations, with the Centers for Disease Control and Prevention estimating that 1.8 million Americans over age 40 have AMD and another 7.3 million Americans have large drusen, which places them at a high risk of developing AMD [1]. Research demonstrates that the relationship between MPOD and central retinal thickness has a strong positive correlation [2], and additional studies show that reduced MPOD is associated with a higher risk of developing AMD [3]. Heterochromatic flicker photometry has been used to measure the spatial profile of MPOD, with two predominant profile types emerging: typical exponential/peaked profile or atypical “central dip” profile [4]. The MARS study by Dietzel et al. [5] found 19.8% of subjects possess this central dip profile, meaning they demonstrate a significantly lower MPOD at retinal eccentricities of 0°, 0.25°, and 0.5° but significantly higher MPOD at 1° and 2° when compared to subjects with no central dip. Concordance between pairs of eyes was labeled as highly significant [5]. The underlying cause of this central dip profile is not well understood, though research showing a higher incidence in certain ethnic populations suggests a genetic link [6,7]. The three primary risk factors for MPOD central dip have been identified as the same three primary risk factors for AMD: age, smoking, and elevated BMI [4,8]. Macular pigment is composed of three carotenoids: lutein (L), RR zeaxanthin (Z), and RS meso-zeaxanthin (Mz). These three molecules are collectively known as xanthophyll carotenoids or macular carotenoids. L and Z have both been wellstudied and are found in many vegetables regularly consumed by humans such as spinach, broccoli, kale, and bell peppers [9]. The role of Mz is not as well understood: it has recently been found in the human food chain in the skin of a handful of species of fish, but only in trace quantities. Research has shown that Mz can be enzymatically derived from L [10], though the relative roles of endogenous Mz isomerization versus dietary consumption of Mz in retinal health remain unstudied (Figure 1-3).