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Nu Eyes Clinical Studies

Nu-Eyes™- Clinical Publication Abstracts

Important Note: We have provided here several abstracts of from research publications, however to review all of the publications regarding the treatment of cataracts with N-Acetylcarnosine eye drops please visit the following public medical database resource www.pubmed.com.

Efficacy of N-Acetylcarnosine in the treatment of cataracts.

Babizhayev MA, Deyev AI, Yermakova VN, Semiletov YA, Davydova NG, Doroshenko VS, Zhukotskii AV, Goldman IM.

PURPOSE: To evaluate the effects of 1% N-acetylcarnosine (NAC) solution on lens clarity over 6 and 24 months in patients with cataracts. TRIAL DESIGN: Randomized, placebo-controlled study.

PARTICIPANTS: 49 subjects (76 affected eyes) with an average age of 65.3 +/- 7.0 years with a diagnosis of senile cataract with minimum to advanced opacification in various lens layers.

METHODS: 26 patients (41 eyes) were allocated to topical NAC 1% eyedrops twice daily. The control group consisted of 13 patients (21 eyes) who received placebo eyedrops and 10 patients (14 eyes) who did not receive eyedrops.

MAIN OUTCOME MEASURES: All patients were evaluated at entry and followed up every 2 months for a 6-month period (trial 1), or at 6-month intervals for a 2-year period (trial 2), for best-corrected visual acuity and glare testing. In addition, cataract was measured using stereocinematographic slit-images and retro-illumination examination of the lens. Digital analysis of lens images displayed light scattering and absorbing centers in two- and three-dimensional scales.

RESULTS: The overall intra-reader reproducibility of cataract measurements (image analysis) was 0.830, and glare testing 0.998. After 6 months, 90% of NAC-treated eyes showed improvement in best corrected visual acuity (7 to 100%) and 88.9% showed a 27 to 100% improvement in glare sensitivity. Topographic studies indicated fewer areas of posterior subcapsular lens opacity and 41.5% of treated eyes had improvement in image analysis characteristics. The overall ratios of image analysis characteristics at 6 months compared with baseline measures were 1.04 and 0.86 for the control and NAC-treated group, respectively (p < 0.001). The apparent benefits of treatment were sustained after 24 months' treatment. No treated eyes demonstrated worsening of vision. The overall visual outcome in the control group showed significant worsening after 24 months in comparison with both baseline and the 6-month follow-up examination. The overall clinical results observed in the NAC-treated group by the 24-month period of examination differed significantly (p < 0.001) from the control group in the eyes with cortical, posterior subcapsular, nuclear or combined lens opacities. Tolerability of NAC eyedrops was good in almost all patients, with no reports of ocular or systemic adverse effects.

CONCLUSION: Topical NAC shows potential for the treatment and prevention of cataracts.

Drugs R D. 2002; 3(2):87-103.

N-Acetylcarnosine, a natural histidine-containing dipeptide, as a potent ophthalmic drug in treatment of human cataracts.

Babizhayev MA, Deyev AI, Yermakova VN, Semiletov YA, Davydova NG, Kurysheva NI, Zhukotskii AV, Goldman IM.

A study was designed to document and quantify the changes in lens clarity over 6 and 24 months in 2 groups of 49 volunteers (76 eyes) with an average age of 65.3 +/- 7.0 enrolled at the time of diagnosis of senile cataracts of minimal to advanced opacification. The patients received N-acetylcarnosine, 1% sol (NAC) (26 patients, 41 eyes = Group II), placebo composition (13 patients, 21 eyes) topically (two drops, twice daily) to the conjunctival sac, or were untreated (10 patients, 14 eyes); the placebo and untreated groups were combined into the control (reference) Group I. Patients were evaluated upon entry, at 2-month (Trial 1) and 6-month (Trial 2)-intervals for best corrected visual acuity (b/c VA), by ophthalmoscopy and the original techniques of glare test (for Trial 1), stereo cinematographic slit-image and retro-illumination photography with subsequent scanning of the lens. The computerized interactive digital analysis of obtained images displayed the light scattering/absorbing centers of the lens into 2-D and 3-D scales. The intra-reader reproducibility of measuring techniques for cataractous changes was good, with the overall average of correlation coefficients for the image analytical data 0.830 and the glare test readings 0.998. Compared with the baseline examination, over 6 months 41.5% of the eyes treated with NAC presented a significant improvement of the gross transmissivity degree of lenses computed from the images, 90.0% of the eyes showed a gradual improvement in b/c VA to 7-100% and 88.9% of the eyes ranged a 27-100% improvement in glare sensitivity. Topographic studies demonstrated less density and corresponding areas of opacification in posterior subcapsular and cortical morphological regions of the lens consistent with VA up to 0.3. The total study period over 24 months revealed that the beneficial effect of NAC is sustainable. No cases resulted in a worsening of VA and image analytical readings of lenses in the NAC-treated group of patients. In most of the patients drug tolerance was good. Group I of patients demonstrated the variability in the densitometric readings of the lens cloudings, negative advance in glare sensitivity over 6 months and gradual deterioration of VA and gross transmissivity of lenses over 24 months compared with the baseline and 6-month follow-up examinations. Statistical analysis revealed the significant differences over 6 and 24 months in cumulative positive changes of overall characteristics of cataracts in the NAC-treated Group II from the control Group I.The N-acetylated form of natural dipeptide L-carnosine appears to be suitable and physiologically acceptable for nonsurgical treatment for senile cataracts.

Peptides. 2001 Jun; 22(6):979-94.

Rejuvenation of visual functions in older adult drivers and drivers with cataract during a short-term administration of N-acetylcarnosine lubricant eye drops.

The purpose of this study was to examine using the original halometer glare test of the type of visual impairment mediated by the increased glare sensitivity (halos) and associated with poorer visual function in both the better and worse eyes of older adult drivers and older drivers with cataract. The clinically validated formula of 1% N-acetylcarnosine (NAC) lubricant eye drops were applied topically to the eyes of older drivers to reduce glare disability and improve distance acuities for driving. This was a randomized, double-blind, placebo-controlled study. The examined subjects consisted of 65 older adults, with cataract in one or both eyes, and 72 adult drivers who did not have cataract in either eye. In the control group, comparison with baseline values showed some variability of data in gradual worsening of glare sensitivity at red and green targets and minimal VA changes over 4 months. In the NAC-treated group, 4-month follow-up generally showed an improvement in VA and a significant improvement in glare sensitivity at red and green targets was documented in worse and better eyes using a critical cut point halometer score for driving. The NAC-treated eyes had statistically significant difference in VA, glare sensitivity compared with the control group ( p < 0.001) at 4-month timepoint of treatment, as supported by the overall t-test results of the ratio of the follow-up data to the baseline values. Tolerability of NAC eyedrops was good in almost all patients, with no reports of ocular or systemic adverse effects. It would be advisable for traffic safety if a Halometer glare sensitivity test was implemented for vehicles and/or was regularly added to the requirements for a driver's licence. The results of this study provide a substantial basis for further evaluation of NAC in the treatment and prevention of vision impairment in the older population of drivers for legal driving. The developed ophthalmic drug NAC formula showed potential for the non-surgical treatment of age-related cataracts.

 Rejuvenation Res. 2004 Fall; 7(3):186-98.

N alpha-acetylcarnosine is a prodrug of L-carnosine in ophthalmic application as antioxidant.

Babizhayev MA, Yermakova VN, Sakina NL, Evstigneeva RP, Rozhkova EA, Zheltukhina GA.
Moscow Helmholtz Research Institute of Eye Diseases, Russian Federation.

The naturally occurring compound N alpha-acetylcarnosine (NAC) is proposed as the prodrug of L-carnosine (C) resistant to enzymatic hydrolysis by human serum carnosinase. Rabbit eyes were treated with 1% NAC, C or placebo and extracts of the aqueous humor from the anterior eye chamber were analyzed for imidazole content by reverse phase analytical high performance liquid chromatography (HPLC), thin-layer (TLC) and ion-exchange chromatographic techniques. The topical administration of pure C to the rabbit eye did not lead to accumulation of this compound in the aqueous humor over 30 min in concentration exceeding that in the placebo-treated matched eye. NAC showed dose-dependent hydrolysis in its passage from the cornea to the aqueous humor, releasing C after 15. 30 min of ocular administration of prodrug in a series of therapeutical modalities: instillation < or = subconjunctival injection < or = ultrasound induced phoresis. Different treatment techniques showed excellent toleration of 1% NAC by the eye. Once in the aqueous humor, C might act as an antioxidant and enter the lens tissue when present at effective concentrations (5-15 mmol/l). The advantage of the ophthalmic prodrug NAC and its bioactivated principle C as universal antioxidants relates to their ability to give efficient protection against oxidative stress both in the lipid phase of biological membranes and in an aqueous environment. NAC is proposed to treat ocular disorders, which have the component of oxidative stress in their genesis (cataracts, glaucoma, retinal degeneration, corneal disorders, ocular inflammation, complications of diabetes mellitus, systemic diseases).

Clin Chim Acta. 1996 Oct 15; 254(1):1-21.
Erratum in: Clin Chim Acta 1997 Mar 18; 259(1-2):199-201.

Revival of the Lens Transparency with N- Acetylcarnosine

Mark A. Babizhayev, Anatoly I. Deyev, Valentina N. Yermakova, Valerii V. Remenshchikov & Johan Bours

The risk, cost and social requirement factors drive the investigation of pharmaceutical approaches to the management of cataracts. The role of free-radical-induced lipid oxidation (LPO) in the development of cataracts has been identified. Initial stages of cataract are characterized by the accumulation of primary (diene conjugates, cetodienes) LPO products,while in later stages there is a prevalence of LPO fluorescent end products. Reliable increase in oxiproducts of fatty acyl content of lenticular lipids was shown by a direct gas chromatography technique producing fatty acid fluorine-substituted derivatives. The lens opacity degree correlates with the level of the LPO fluorescent end product accumulation in its tissue, accompanied by SH group oxidation of lens proteins due to a decrease of reduced glutathione concentration in the lens. The injection of LPO products into the vitreous was shown to induce cataract. Peroxide damage of the lens fiber membranes may be the initial cause of cataract formation. The authors developed N-Acetylcarnosine ophthalmic drug with lubricant carboxymethylcellulose in eye drops (NAC, Nu-EyesTM) suitable for the non-surgical prevention and treatment of age-related cataracts. The NAC ophthalmic drug protects the crystalline lens from oxidative stress-induced damages and in a recent clinical trial it was shown to produce an effective, safe and long-term improvement in sight. When administered topically to the eye, NAC drug functions as a time–release prodrug form of L-carnosine resistant to hydrolysis with carnosinase and significantly increases the intraocular uptake of L-carnosine in the aqueous humor. The mechanisms of prevention and reversal of cataracts with NAC ophthalmic drug are considered which include prevention by the intraocular released carnosine of free-radical-induced inactivation of proprietary lens antioxidant enzymes (superoxide dismutase), prevention of carbohydrate and metal-catalysed autooxidation of ascorbic acid –induced cross-linking glycation reactions to the lens proteins, universal antioxidant and scavenging activity towards lipid hydroperoxides, aldehydes and oxygen radicals, activation with L-carnosine ingredient of proteasome activity in the lens. In this study the clinical effects of a topical solution of NAC ophthalmic drug on lens opacities were examined in patients with cataracts and canines with age-related cataracts. The positive effect on lens clarity and clarifying modification of opacification zones is demonstrated. The data suggest a potential and show the efficacy of developed NAC ophthalmic drug for a positive effect of treatment of age-related cataracts.

Current Drug Therapy 2006 January; 1(1):91-116