Hair cortisol level as a molecular biomarker in retinitis pigmentosa patients.

PURPOSE: Retinitis pigmentosa (RP) patients commonly experience negative psychological states due to their progressive and unpredictable loss of vision and visual variations related to stress. The aim of this study was to examine hair cortisol concentrations (HCCs), which is usually associated with chronic stress, pretending to unveil possible associations between underlying psychological factors and disease severity in RP patients. METHODS: Seventy-eight RP patients and 148 healthy controls were included in this study. A complete ophthalmological exam was performed in all patients to grade into severity disease groups. Perceived stress and trait-anxiety were measured by the State-Trait Anxiety Inventory (STAI) questionnaire. RESULTS: Fifty-two (67%) patients had severe RP and 26 (33%) mild-moderate RP. Fifty-eight (58,9%) patients reported severely levels of stress and 18 (23.,1%) highly levels assessed by STAI questionnaire. RP patients exhibited higher HCCs (500.04 ± 120.99 pg/mg) than in controls (136.17 ± 60.51 pg/mg; p < 0.001). Severe RP patients had significant higher HCCs than mild-moderate patients differing in 274.27 pg/mg (p < 0.001). RP severity grade and perceived anxiety levels in the questionaries were not associated. Group differences were not affected by relevant covariates (age, grade of severity, stress status, and gender). CONCLUSIONS: HCC seems an effective biomarker associated with chronic stress in RP patients. This study shows that HCC in patients with RP are elevated compared to population-based controls, and association between HCC and RP severity was found. Future research is needed to characterize the effect of untreated negative psychological states on progression of the disease if any.

Effectiveness and safety of nutritional supplements in the treatment of hereditary retinal dystrophies: a systematic review.

The hereditary retinal dystrophies (HRDs) are a group of genetically determined disorders that result in loss of the visual function. There is a lack of standard pharmacological treatments or widely accepted nutritional recommendations. The objective of this review is to summarise the scientific evidence on the effectiveness and safety of nutritional supplements for the treatment of HRDs. We conducted a scientific literature search on Medline and PreMedline, EMBASE, SCI-EXPANDED, SSCI, and The Cochrane Library up to August 2014. Experimental, quasi-experimental and controlled observational studies were selected. Eight studies were ultimately included, seven on retinitis pigmentosa (RP) and one on Best disease. Vitamin A, vitamin E, docosahexaenoic acid (DHA), lutein and ß-carotene were assessed. A 15 000 IU daily dose of vitamin A was reported to have shown a small protective effect on the progression of RP, as was the use of the carotenoids lutein and ß-carotene. Different DHA doses has no effect on RP or Best disease. No supplement showed severe adverse effects in the selected studies although strong evidence of toxicity exists for high doses of vitamin A and ß-carotene in certain populations. The selected studies concluded that there may be a small beneficial effect of vitamin A, lutein and ß-carotene on the progression of RP. The limited evidence available indicates some well-designed additional studies on combined supplements strategies may achieve more robust conclusions. Moreover, the scarcity of evidence available on the treatment of HRD other than RP with nutritional supplements supports the need for further research efforts.

Pharmacokinetics of 0.5 mg of a single and a multiple dose of intravitreal vancomycin in infected rabbit eyes.

The purpose of this study was to determine the pharmacokinetics governing distribution and elimination of 0.5 mg of intravitreal vancomycin in a single dose and in a multiple therapeutic regime in infected rabbit eyes. A total of 96 rabbits was injected with approximately 200 CFU of S. aureus intravitreally. Four days later, a single dose of 0.5 mg of vancomycin was administered to Group I (n=36). Group II (n=60) was injected with a maximum of 4 doses of 0.5 mg every 36 hr. Four animals were sacrificed at different time points in each group. Samples of vitreous, aqueous and blood were taken from each animal for analyses by HPLC. These results were evaluated using the RSTRIP program. High vancomycin concentrations were demonstrated in the vitreous of Group I, with a calculated half-life of 12 hr. In Group II, vancomycin levels were within the therapeutic range during the entire experiment. There was minimal accumulation of the drug, and the half-life did not seem to be longer with multiple doses. In conclusion, the pharmacokinetics do not change significantly when a multidose regime is used compared with a single dose. Therapeutic intravitreal concentrations of vancomycin can be achieved by using repeated doses of 0.5 mg of vancomycin.

Pharmacokinetics of intravitreal vancomycin in normal and infected rabbit eyes.

The purpose of this study was to determine the pharmacokinetics governing the distribution and elimination of intravitreally injected vancomycin in normal and infected rabbit eyes. Two groups each of 36 pigmented animals were used. Group 1 served as control. In Group 2, experimental endophthalmitis was induced in the right vitreous by inoculation with Staphylococcus aureus. Once endophthalmitis developed, a vancomycin solution was injected. Four animals from each group were killed at nine time points post-injection, the vitreous and aqueous were removed, and blood samples were taken for HPLC analysis. Data analysis was performed using the RSTRIP program. The half-lives were 69 hours in normal vitreous and 14.53 hours in infected vitreous. Therapeutic drug levels were present in the vitreous 84 hours post-injection in all eyes; they were detected from 2 to 48 hours in normal aqueous but at lower levels in the infected ones. Kv and Ca/Cv ratios suggested that the primary route of elimination was across the retina and the anterior chamber in normal eyes, and via the retina in infected eyes. Results indicate that pharmacokinetic parameters change in pathological conditions, which may help establish better treatment guidelines for endophthalmitis.