Drusen regression is associated with local changes in fundus autofluorescence in intermediate age-related macular degeneration.

PURPOSE: To investigate the association of spontaneous drusen regression in intermediate age-related macular degeneration (AMD) with changes on fundus photography and fundus autofluorescence (FAF) imaging. DESIGN: Prospective observational case series. METHODS: Fundus images from 58 eyes (in 58 patients) with intermediate AMD and large drusen were assessed over 2 years for areas of drusen regression that exceeded the area of circle C1 (diameter 125 µm; Age-Related Eye Disease Study grading protocol). Manual segmentation and computer-based image analysis were used to detect and delineate areas of drusen regression. Delineated regions were graded as to their appearance on fundus photographs and FAF images, and changes in FAF signal were graded manually and quantitated using automated image analysis. RESULTS: Drusen regression was detected in approximately half of study eyes using manual (48%) and computer-assisted (50%) techniques. At year-2, the clinical appearance of areas of drusen regression on fundus photography was mostly unremarkable, with a majority of eyes (71%) demonstrating no detectable clinical abnormalities, and the remainder (29%) showing minor pigmentary changes. However, drusen regression areas were associated with local changes in FAF that were significantly more prominent than changes on fundus photography. A majority of eyes (64%-66%) demonstrated a predominant decrease in overall FAF signal, while 14%-21% of eyes demonstrated a predominant increase in overall FAF signal. CONCLUSIONS: FAF imaging demonstrated that drusen regression in intermediate AMD was often accompanied by changes in local autofluorescence signal. Drusen regression may be associated with concurrent structural and physiologic changes in the outer retina.

Corticosteroid-associated osteonecrosis: a rare, but serious, complication in uveitis.

PURPOSE: To examine the incidence and prevalence of osteonecrosis in uveitis patients. METHODS: An electronic medical record database search was conducted to identify uveitis patients with osteonecrosis and the number at risk for corticosteroid-related osteonecrosis from 2003 to 2012. The clinical and ophthalmologic features of the uveitis patients with osteonecrosis were assessed with retrospective chart reviews. RESULTS: Six uveitis patients with osteonecrosis were identified, comprising a prevalence of 1.5%. The incidence density was 0.19 per 100 person-years of follow-up. The uveitides included sarcoidosis, sympathetic ophthalmia, idiopathic retinal vasculitis, idiopathic chronic anterior and intermediate uveitis, Vogt-Koyanagi Harada disease, and Cogan syndrome. The duration of systemic corticosteroid treatment ranged from 6 weeks to 6 years. The potential systemic risk factors were Raynaud phenomenon, antiphospholipid and autoantibodies, sickle cell trait, and thalassemia. CONCLUSIONS: Although osteonecrosis appears to be a rare complication among uveitis patients, physicians should strive to minimize systemic corticosteroid use when appropriate. A higher level of suspicion for osteonecrosis may be warranted in patients with additional systemic risk factors.

Subconjunctival sirolimus in the treatment of diabetic macular edema.

BACKGROUND: Diabetic macular edema (DME) is a leading cause of blindness in the developed world. Sirolimus has been shown to inhibit the production, signaling, and activity of many growth factors relevant to the development of diabetic retinopathy. This phase I/II study assesses the safety of multiple subconjunctival sirolimus injections for the treatment of DME, with some limited efficacy data. METHODS: In this phase I/II prospective, open-label pilot study, five adult participants with diabetic macular edema involving the center of the fovea and best-corrected ETDRS visual acuity score of ≤74 letters (20/32 or worse) received 20 µl (440 µg) of subconjunctival sirolimus at baseline, month 2 and every 2 months thereafter, unless there was resolution of either retinal thickening on OCT or leakage on fluorescein angiography. Main outcome measures included best-corrected visual acuity and central retinal thickness on OCT at 6 months and 1 year, as well as safety outcomes. RESULTS: Repeated subconjunctival sirolimus injections were well-tolerated, with no significant drug-related adverse events. There was no consistent treatment effect related to sirolimus; one participant experienced a 2-line improvement in visual acuity and 2 log unit decrease in retinal thickness at 6 months and 1 year, two remained essentially stable, one had stable visual acuity but improvement of central retinal thickness of 1 and 3 log units at 6 months and 1 year respectively, and one had a 2-line worsening of visual acuity and a 1 log unit increase in retinal thickness at 6 months and 1 year. Results in the fellow eyes with diabetic macular edema, not treated with sirolimus, were similar. CONCLUSIONS: Subconjunctival sirolimus appears safe to use in patients with DME. Assessment of possible treatment benefit will require a randomized trial.

Nutritional supplements for age-related macular degeneration.

PURPOSE OF REVIEW: Age-related macular degeneration (AMD), a leading cause of visual loss in older adults, has limited therapeutic options. This review describes the current literature on the role of nutritional supplementation in primary and secondary prevention of AMD. RECENT FINDINGS: Many observational studies have explored the association between diet, nutrient intake, and AMD. In particular, high dietary intakes of omega-3 fatty acids, and macular xanthophylls lutein and zeaxanthin have been associated with a lower risk of prevalent and incident AMD. However, the Age-Related Eye Disease study (AREDS) is the only large-scale randomized controlled clinical trial to show a 25% beneficial effect of nutritional supplementation in reducing the risk progression to advanced AMD in patients with intermediate AMD or with advanced AMD in one eye at 5 years of follow-up. On the basis of the results of AREDS, these patients are recommended to take AREDS formulation of vitamins C, E, beta-carotene, and zinc with copper. SUMMARY: At the present time, there is insufficient evidence in the literature to recommend routine nutritional supplementation in healthy adults for primary prevention of AMD. However, patients with intermediate risk of AMD or advanced AMD in one eye should consider taking AREDS-type supplements. Observational studies have also suggested benefit from increased dietary intake of macular xanthophylls and omega-3 fatty acids. These are currently being evaluated prospectively in a randomized controlled clinical trial, the AREDS2.

Treatment of agitation following traumatic brain injury: a review of the literature.

Agitation, restlessness, and aggression are frequent neurobehavioural sequelae in the early stages of recovery from traumatic brain injury (TBI). These behavioural symptoms disrupt patient care and impede rehabilitation efforts. We review the current literature (1985 onwards) examining the pharmacological management of post-TBI agitation in both acute and post-acute conditions. This article will assess the evidence for the use of selected alkylphenols, benzodiazepines, estrogens, antiandrogens, neuroleptics/antipsychotics, antidepressants, anti-Parkinsonian agents, antipsychotics, anticonvulsants, lithium carbonate, buspirone, beta-blockers, and psychostimulants in agitated TBI survivors. Review of the literature suggests that there is limited evidence to accurately guide clinicians in the management of this patient population.

Lycopene I--effect on osteoclasts: lycopene inhibits basal and parathyroid hormone-stimulated osteoclast formation and mineral resorption mediated by reactive oxygen species in rat bone marrow cultures.

Osteoclasts have been shown to produce reactive oxygen species (ROS) that can stimulate bone resorption. We explored the hypothesis that lycopene, the antioxidant carotenoid from tomatoes, can inhibit mineral resorption by inhibiting osteoclast formation and the production of ROS. Cells from bone marrow prepared from rat femur were plated into 16-well calcium phosphate-coated Osteologic Multi-test Slides and cultured in alpha-minimal essential medium supplemented with dexamethasone, beta-glycerophosphate, and ascorbic acid. The cells were treated with varying doses of lycopene in the absence or presence of parathyroid hormone (PTH) at the start of culture and at each medium change (i.e., every 48 hours). On day 8, mineral resorption pits were quantitated. Similar, parallel experiments were carried out in 12-well plastic dishes to assess tartrate-resistant acid phosphatase (TRAP) activity. Results showed that lycopene inhibited TRAP + formation of multinucleated cells in both vehicle- and PTH-treated cultures. Osteoclasts reduced nitroblue tetrazolium (NBT) to purple-colored formazan, indicating the presence of ROS in these cells. The formazan-staining cells were decreased by treatment with 10(-5) M lycopene, indicating that lycopene inhibited the formation of ROS-secreting osteoclasts. In conclusion, we have shown that lycopene inhibits basal and PTH-stimulated osteoclastic mineral resorption and formation of TRAP + multinucleated osteoclasts, as well as the ROS produced by osteoclasts. These findings are novel and may be important in the pathogenesis, treatment, and prevention of osteoporosis.