The gap between the need for novel retinal drug delivery methods, technologies in R&D phase, and approved ocular drug delivery technologies.

The past four decades were marked by the realization that the delivery of drugs into the eye is a crucial step in the development and utilization of new ocular drugs. This realization led to vast efforts and investments in research and development (R&D) to improve and approve new technologies. The realization of intravitreal injections and the vast utilization of this methodology in retinal disease management deepened the need for new drug delivery methods for drugs already approved safe and effective. Yet, there are only a handful of technologies approved and in clinical use today. Here, we focus on this gap by highlighting bottlenecks and by encouraging creative thinking for solutions.

Kynurenic Acid and Neuroprotective Activity of the Ketogenic Diet in the Eye.

BACKGROUND: There is growing evidence of the involvement of the kynurenine metabolic pathway and the enhancement of kynurenic acid production in the neuroprotective effects of the ketogenic diet. OBJECTIVE: Here, we review evidence implicating kynurenic acid in the efficacy of ketogenic diet in eye diseases associated with neurodegeneration. FINDINGS: Ketogenic diet and ketone bodies that are elevated during exposure to the ketogenic diet each have a neuroprotective effect on retinal ganglion cells in a rat model of Nmethyl- D-aspartate induced neuronal damage. Chronic exposure to ketogenic diet also increases kynurenic acid concentrations in discrete rat brain structures. A non-selective glutamate receptor agonist, glutamate, also decreases the production of kynurenic acid in bovine retinal slices; this effect is attenuated by acetoacetate and ß-hydroxybutyrate, two of three ketone bodies overproduced during ketogenic diet. PERSPECTIVE: Whether ketogenic diet induced enhancement of kynurenic acid production would translate into a clinically significant improvement in certain eye diseases like glaucoma and retinal neurodegenerations awaits further experimental and clinical verification.

The antioxidants in the process of ocular pathology / Los antioxidantes en el proceso de patologías oculares

Introduction: The influence of antioxidants on ocular processes has taken on a significant importance in recent years for its effects on visual health. Oxidative stress is a factor involved in the development of major pathologies such as cataracts, glaucoma and age-related macular degeneration (AMD). Objective: To establish the scientific evidence that exists about the different types of antioxidants and their effects on ocular pathological processes through a systematic review. Methods: Literature search in MEDLINE, Scielo and Cochrane for studies evaluating the use of antioxidants in the prevention and/or treatment of eye diseases. Selected randomized controlled clinical trials over the past 7 years were selected. Results: The relationship between different types of antioxidants, vitamin E, C, beta carotene, zinc, lutein, anthocyanins and carotenoids, suggests a positive relationship with the risk and progression of AMD and glaucoma parameters, indicating a lower risk of the disease due to an increased consumption of antioxidants in the diet. Initial reports suggest a potential role for diet modification in the treatment of age-related macular degeneration and glaucoma primarily, not evidencing for the prevention of cataract. Conclusions: Promoting adequate consumption of antioxidants in the diet can prevent and protect against highly prevalent eye diseases. The antioxidants of the group of vitamins are the most studied so far in the ocular pathologies. More clinical trials are needed to establish these relationships more precisely.

Introducción: la influencia de los antioxidantes en los procesos oculares ha tomado en los últimos años una relevancia importante por sus efectos en la salud visual. El estrés oxidativo es un factor implicado en el desarrollo de las principales patologías tales como cataratas, glaucoma y degeneración macular asociada a la edad (DMAE). Objetivo: establecer la evidencia científica que existe sobre los distintos tipos de antioxidantes y sus efectos en procesos patológicos oculares mediante una revisión sistemática. Métodos: búsqueda bibliográfica en MEDLINE, Scielo y Cochrane de estudios que evalúan la utilización de antioxidantes en la prevención y/o tratamiento de las enfermedades oculares. Se seleccionaron ensayos clínicos controlados y aleatorizados publicados en los últimos 7 años. Resultados: la relación entre distintos tipos de antioxidantes, vitamina E, C, betacaroteno, zinc, luteína, antocianinas y carotenoides, sugiere una relación positiva ante el riesgo y progresión de DMAE y parámetros del glaucoma, indicando un menor riesgo de la enfermedad ante un mayor consumo de antioxidantes en la dieta. Informes iniciales sugieren un papel potencial para la modificación de la dieta en el tratamiento de la degeneración macular asociada a la edad y glaucoma principalmente, no evidenciándose para la prevención de la catarata. Conclusiones: promover el consumo adecuado de antioxidantes en la dieta puede prevenir y proteger frente a patologías oculares de gran prevalencia. Los antioxidantes del grupo de vitaminas son los más estudiados hasta el momento en las patologías oculares. Es necesario llevar a cabo más ensayos clínicos para establecer de forma más precisa estas relaciones.

La historia clínica en pacientes oftalmológicos tratados con complejos multivitamínicos / Clinical history in ophthalmological patients treated with multivitamin complexes

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Antioxidants and vision health: facts and fiction.

A number of nutritional supplements containing antioxidants are advertised for better vision health. Do they benefit the average consumer? The literature was examined for the effectiveness of antioxidants for human eye health, and for the intricacies in collection of such evidence. The following diseases were considered: cataract, glaucoma, age-related macular degeneration (AMD), retinopathy, retinitis pigmentosa, eye infections, and uveitis. The literature indicates that antioxidant supplements plus lutein have a reasonable probability of retarding AMD. For glaucoma, such supplements were ineffectual in some studies but useful in others. In some studies, antioxidant rich fruits and vegetables were also useful for protection against glaucoma. For diabetic retinopathy, antioxidant supplements may have a small benefit, if any, but only as an adjunct to glycemic control. In very high-risk premature retinopathy and retinitis pigmentosa, antioxidant supplements may be beneficial but those with excess Vitamin E should be avoided. For cataract, there is no evidence for an advantage of such nutritional supplements. However, lubricant drops containing N-acetylcarnosine may be helpful in initial stages of the disease. For eye infections and other causes of uveitis, antioxidants have not been found useful. We recommend that a diet high in antioxidant rich foods should be developed as a habit from an early age. However, when initial signs of vision health deterioration are observed, the appropriate nutritional supplement products may be recommended but only to augment the primary medical treatments.

The role of lutein in eye-related disease.

The lens and retina of the human eye are exposed constantly to light and oxygen. In situ phototransduction and oxidative phosphorylation within photoreceptors produces a high level of phototoxic and oxidative related stress. Within the eye, the carotenoids lutein and zeaxanthin are present in high concentrations in contrast to other human tissues. We discuss the role of lutein and zeaxanthin in ameliorating light and oxygen damage, and preventing age-related cellular and tissue deterioration in the eye. Epidemiologic research shows an inverse association between levels of lutein and zeaxanthin in eye tissues and age related degenerative diseases such as macular degeneration (AMD) and cataracts. We examine the role of these carotenoids as blockers of blue-light damage and quenchers of oxygen free radicals. This article provides a review of possible mechanisms of lutein action at a cellular and molecular level. Our review offers insight into current clinical trials and experimental animal studies involving lutein, and possible role of nutritional intervention in common ocular diseases that cause blindness.

Calorie restriction (CR) and CR mimetics for the prevention and treatment of age-related eye disorders.

The morbidity of ocular diseases, including macular degeneration, diabetic retinopathy, and dry eye disease, has been gradually increasing worldwide. Because these diseases develop from age-associated ocular dysfunctions, interventions against the aging process itself may be a promising strategy for their management. Among the several approaches to interrupt aging processes, calorie restriction (CR) has been shown to recover and/or slow age-related functional declines in various organs, including the eye. Here, we review interventions against the aging process as potential therapeutic approaches to age-related ocular diseases. The effects of CR and CR mimetics in animal models of age-related eye diseases are explored. Furthermore, we discuss the possibilities of expanding this research to prospective studies to elucidate the molecular mechanisms by which CR and/or CR mimetics preserve ocular functions.

Informing food choices and health outcomes by use of the dietary glycemic index.

Considerable epidemiologic evidence links consuming lower glycemic index (GI) diets with good health, particularly upon aging. The GI is a kinetic parameter that reflects the ability of carbohydrate (CHO) contained in consumed foods to raise blood glucose in vivo. Newer nutritional, clinical, and experimental data link intake of lower dietary GI foods to favorable outcomes of chronic diseases, and compel further examination of the record. Based upon the new information there are two specific questions: 1) should the GI concept be promoted as a way to prolong health, and 2) should food labels contain GI information? Further, what are the remaining concerns about methodological issues and consistency of epidemiological data and clinical trials that need to be resolved in order to exploit the benefits of consuming lower GI diets? These issues are addressed in this review.

Estado nutricio de vitamina A en preescolares con padecimientos oculares / Nutritional status of vitamin A in preschoolers with ocular diseases

El propósito del estudio fue evaluar el estado nutricio de vitamina A en preescolares con padecimientos oculares que acuden al Hospital Civil de Guadalajara. En estudio transversal analítico se incluyeron por conveniencia 100 sujetos (24-71 meses) con padecimiento ocular. El consumo de vitamina A (VA), energía y macro nutrimentos se estimó con una encuesta dietética de recordatorio de 24 horas (EDR-24h). Mediante cromatografía líquida de alta presión (HPLC) se determinó la concentración sérica de retinol y se realizó una citología de impresión conjuntival (CIC) por un patólogo entrenado en la técnica. Se estimaron los índices talla/edad y peso/talla (Puntaje z) y se utilizaron las pruebas de ANOVA, U de Mann Whitney y de correlación de Spearman. Fueron niñas 44,1 por ciento y varones 55.9 por ciento. Los padecimientos oculares más frecuentes fueron: estrabismo (41,9 por ciento), conjuntivitis (19,4 por ciento) y padecimientos congénitos (17,2 por ciento). Según la EDR-24 h el consumo de vitamina A fue de 374 µg/día ± 706; la concentración de Retinol sérico 30 µg/dL ± 7,6 y CIC fue normal en 75,6 por ciento. Sólo 3.2 por ciento a 3,5 por ciento presentaron deficiencia de VA (concentración de retinol y CIC). No hubo asociación entre padecimientos oculares y deficiencia de VA. Hubo correlación positiva entre consumo de vitamina A e índice peso/talla (r = 0,244). En conclusión, la mayoría de los preescolares cubrió la ingestión recomendada de vitamina A, la deficiencia de esta vitamina fue baja y no se asoció a padecimientos oculares.

SUMMARY The purpose was to evaluate the nutritional status of vitamin A in preschool children with ocular diseases attending to the Hospital Civil of Guadalajara. In a cross sectional design 100 preschool children between 24 and 71 mo of age with ocular diseases were included. Vitamin A intake was evaluated by 24 h dietetic recall, plasma Retinol concentration by high pressure liquid chromatography (HPLC); and, conjunctiva impression cytology (CIC) was carried out by a trained pathologist. ANOVA and U Mann Whitney tests, and also Spearman correlations were estimated. There were 44.1 percent females and 55,9 percent males. Strabismus was the most common disease (41,9 percent), conjunctivitis (19,4 percent), and congenital diseases (17,2 percent). The mean intake of Vitamin A was 374 µg/d ± 706 and the serum concentration of retinol was of 30 µg/dL ± 7,6; CIC was normal in 75,6 percent. The percentage of vitamin A deficiency was 3,2 percent according to the serum concentration of Retinol and 3,5 percent to the CIC criteria. It was not association between the nutritional status of vitamin A and ocular diseases. A positive correlation between vitamin A intake and weight/height index (r = 0,244) was found. In conclusion, most preschool children covered the dietary reference intake recommendation of vitamin A; deficiency of this vitamin was lower and, it was not associated to ocular diseases.

Iris diagnosis.

Iris diagnosis is a useful method of assessment that offers the potential to expand the physician's understanding of a patient's overall state of health and vitality, and of the aetiology of disease processes. As it becomes refined by research around the world (mostly in Germany at present), its accuracy in predicting organ disease already quite remarkable, continues to improve. Iris diagnosis offers a useful and quick screening method that may alert the physician to underlying problems as an aid to the holistic physician in nutritional counseling.

Relationship between hemorrhagic ocular diseases and vitamin C deficiency: clinical and experimental data.

The hematic level of ascorbic acid was significantly lower with respect to that of healthy subjects in 55 patients with hemorrhagic ocular diseases. Experiments on albino guinea pigs showed that an induced hypovitaminosis C (2 weeks of scorbutigenic diet followed by a maintenance dose of 0,5 mg of ascorbic acid) caused the appearance of widespread retina hemorrhages and a significant decrease of the blood ascorbate levels with respect to the control groups. The present results suggest that a prolonged insufficient dietary intake of ascorbic acid may give rise to hemorrhagic ocular pathologies in humans.