Fracture Prevention with Zoledronate in Older Women with Osteopenia.

BACKGROUND: Bisphosphonates prevent fractures in patients with osteoporosis, but their efficacy in women with osteopenia is unknown. Most fractures in postmenopausal women occur in those with osteopenia, so therapies that are effective in women with osteopenia are needed. METHODS: We conducted a 6-year, double-blind trial involving 2000 women with osteopenia (defined by a T score of -1.0 to -2.5 at either the total hip or the femoral neck on either side) who were 65 years of age or older. Participants were randomly assigned to receive four infusions of either zoledronate at a dose of 5 mg (zoledronate group) or normal saline (placebo group) at 18-month intervals. A dietary calcium intake of 1 g per day was advised, but calcium supplements were not provided. Participants who were not already taking vitamin D supplements received cholecalciferol before the trial began (a single dose of 2.5 mg) and during the trial (1.25 mg per month). The primary end point was the time to first occurrence of a nonvertebral or vertebral fragility fracture. RESULTS: At baseline, the mean (±SD) age was 71±5 years, the T score at the femoral neck was -1.6±0.5, and the median 10-year risk of hip fracture was 2.3%. A fragility fracture occurred in 190 women in the placebo group and in 122 women in the zoledronate group (hazard ratio with zoledronate, 0.63; 95% confidence interval, 0.50 to 0.79; P<0.001). The number of women that would need to be treated to prevent the occurrence of a fracture in 1 woman was 15. As compared with the placebo group, women who received zoledronate had a lower risk of nonvertebral fragility fractures (hazard ratio, 0.66; P=0.001), symptomatic fractures (hazard ratio, 0.73; P=0.003), vertebral fractures (odds ratio, 0.45; P=0.002), and height loss (P<0.001). CONCLUSIONS: The risk of nonvertebral or vertebral fragility fractures was significantly lower in women with osteopenia who received zoledronate than in women who received placebo. (Funded by the Health Research Council of New Zealand; Australian New Zealand Clinical Trials Registry number, ACTRN12609000593235 .).

Investigação oftalmológica pré-clínica do óleo essencial de Origanum vulgare L. Lamiaceae / Ophthalmological pre-clinical research about essential oil from the Origanum vulgare L. Lamiaceae

RESUMO Objetivo: Avaliar a irritação ocular aguda em coelhos, após a administração tópica de óleo essencial. Métodos: Para tanto, os animais foram divididos em três grupos, cada um com três coelhos, totalizando 6 olhos por grupo, e a diferença entre eles foi a concentração utilizada ( 1, 3 e 9%). Aplicou-se no saco conjuntival, de um dos olhos do animal, uma dose única de 0,1 ml do produto e o olho contralateral foi usado como controle. Analisou-se os efeitos causados pelo óleo essencial na conjuntiva, íris e córnea após 1, 24, 48, 72 horas e no final do sétimo dia após a aplicação tópica. As avaliações oftalmológicas foram feitas com o auxílio de um oftalmoscópio binocular indireto com e sem fluoresceína. As reações observadas foram graduadas segundo a escala de Draize. Foram realizados exames anatomopatológicos em todos os olhos estudados no final do experimento. Resultados: No grupo de animais submetidos à instilação ocular do óleo essencial a 1%, não se observou alterações. O tratamento com o óleo a 3% provocou alteração conjuntival no exame feito em 1 hora, o que foi reduzindo. A administração do óleo essencial a 9% induziu hiperemia conjuntival, não havendo qualquer alteração nos outros tempos de avaliação oftalmológica. Conclusão: A avaliação contribuiu para conhecer as alterações clínicas na superfície ocular. Desta forma, foi possível classificar o óleo a 1% como não irritante e nas concentrações de 3 e 9% como pouco irritante, tornando possível estudos clínicos, a fim de estabelecer o óleo como alternativa terapêutica em conjuntivites bacterianas.

ABSTRACT Objective: To evaluate acute eye irritation in rabbits following topical administration of essential oil. Methods: animals were divided into three groups, each containing three rabbits, with a total of 6 eyes per group. The difference between them was the concentration used (1, 3 and 9%). A single dose of 0.1 ml of the product was applied into the conjunctival sac of one eye of the animal, and the contralateral eye was used as control. The effects caused by the essential oil in the conjunctiva, iris and cornea were analyzed after 1, 24, 48 and 72 hours and at the end of the seventh day after topical application. Ophthalmologic evaluations were performed with the aid of a binocular indirect ophthalmoscope fluorescein and with and without the observed responses, before being graded according to the Draize scale. Pathological examinations were performed on all eyes studied at the end of the experiment. Results: in the group of animals subjected to the ocular instillation of 1% essential oil, there was no change. For treatment with 3% oil, conjunctival changes were found to be decreasing during the examination after 1 hour. Administration of the 9%essential oil induced conjunctival injection, without any change in the other ophthalmologic evaluation times. Conclusion: the evaluation contributed to meet the clinical changes in the ocular surface. Thus, it was possible to classify the oil at 1% as non-irritating and the concentration of 3% and 9 as mildly irritating, making it possible for clinical studies to establish the oil as an alternative therapy in bacterial conjunctivitis.

Bilateral Iritis after Vaccine for Bladder Cancer.

PURPOSE: Bacille Calmette-Guérin (BCG) is a vaccine that can be instilled into the urinary bladder as immunotherapy against superficial bladder cancer. Several case reports have implicated intravesical BCG in the development of uveitis. Patients treated with BCG therapy may present with systemic symptoms resembling reactive arthritis and, less frequently, have ocular adverse effects including bilateral panuveitis or chorioretinitis. In all but three previously reported cases of uveitis associated with BCG treatment, HLA-B27 has been positive. No patients have been reported to be positive for rheumatoid factor or antinuclear antibody (ANA). CASE REPORT: An HLA-B27-negative and low-positive ANA patient presented with bilateral uveitis after treatment with BCG therapy for superficial bladder cancer. CONCLUSIONS: There is a need for greater awareness among urologists, primary care physicians, and optometrists of the potential for BCG to cause uveitis. These doctors should look for indicators of uveitis, such as circumlimbal conjunctival injection, photophobia, irregular pupils, and keratic precipitates. Together with appropriate treatment or prompt referral, this could prevent unnecessary morbidity. Future studies are needed to further elucidate the possible reasons for ANA positivity in these patients and the future role of the test in diagnosis and management.

Intravitreal aflibercept after bilateral bevacizumab-induced iritis.

PURPOSE: To present a case of neovascular age-related macular degeneration treated with aflibercept intravitreal injections after bilateral bevacizumab injections, administered on separate dates, resulted in bilateral iritis. CASE REPORT: A 73-year-old woman with a previous history of two episodes of nongranulomatous iritis in her right eye that was believed to be associated with her systemic diagnosis of rheumatoid arthritis was treated with intravitreal bevacizumab injections for bilaterally occurring neovascular age-related macular degeneration. Initial bevacizumab injections in each eye administered sequentially over a week's time resulted in immediate-onset nongranulomatous iritis in each eye. Subsequent intravitreal injections of aflibercept were administered, and therapeutic benefit was achieved without occurrence of iritis. CONCLUSIONS: In cases where intravitreal bevacizumab results in anterior uveitis, aflibercept may be a safe alternative therapeutic choice for the treatment of neovascular age-related macular degeneration.

Acute anterior uveitis following intravitreal injection of bevacizumab.

BACKGROUND AND OBJECTIVE: To report five cases of iritis after intravitreal injection of bevacizumab. PATIENTS AND METHODS: The clinical charts of patients who received intravitreal injections of bevacizumab or ranibizumab from January 2009 to September 2011 by one physician were retrospectively reviewed. RESULTS: A total of 1,097 injections of bevacizumab and 571 of ranibizumab were administered. Five patients developed acute anterior uveitis and presented with severe pain, photophobia, conjunctival injection, and anterior chamber reaction 2 to 24 hours after intravitreal injection of bevacizumab. All five patients were treated with topical corticosteroids with rapid resolution of the inflammation. CONCLUSION: Although uncommon, acute iritis is a complication of intravitreal injection of bevacizumab.

Assessment of anterior chamber inflammation after intravitreal bevacizumab injection in different ocular exudative diseases.

PURPOSE: To investigate the inflammation of the anterior chamber after intravitreal bevacizumab injection in different ocular exudative diseases. METHODS: The study included 76 eyes from 62 consecutive patients with different ocular exudative diseases. The patients were divided into the 3 following groups: group 1 (nonproliferative diabetic retinopathy), group 2 (choroidal neovascularization secondary to age-related macular degeneration), and group 3 (macular edema with branch or central retinal vein occlusion). The study also included 32 age-matched control patients. Inflammation of the anterior chamber was examined with flare-cell photometry before and after an intravitreal injection of 1.25 mg of bevacizumab. RESULTS: There were no statistically significant differences between the measurements at baseline and postoperative day 1, 3, 7, or 30 in any of the groups (p>0.05). CONCLUSIONS: The extent of inflammation in the anterior chamber did not change after intravitreal bevacizumab injection in patients with nonproliferative diabetic retinopathy, choroidal neovascularization secondary to age-related macular degeneration, or macular edema due to branch or central vein occlusion.

Etanercept therapy-associated acute uveitis: a case report and literature review.

A female patient diagnosed with ankylosing spondylitis experienced a new onset acute iritis following the initiation of etanercept therapy and recurrent episodes of iritis continues during the treatment of etanercept. Etanercept-associated iritis was suspected. Anti-TNF therapies can alleviate uveitis in some studies, but in some other anecdotal reports etanercept is considered as the main cause of uveitis. A literature review is presented below. For clinicians, more attention must be paid to the potential association between uveitis or iritis and etanercept, and more careful surveillance of patients under etanercept treatment is necessary.

Putative side effects of prostaglandin analogs.

Anecdotal case reports describe the occurrence of cystoid macular edema, iritis, herpes simplex keratitis, periocular skin darkening, and headaches in patients treated with prostaglandin analogs for glaucoma. The purpose of this article is to critically analyze these anecdotal case reports in light of a few well-controlled, randomized clinical studies to determine whether conclusions can be made about a causal relationship between the use of prostaglandin analogs and the occurrence of these side effects. None of these putative side effects has been proven to be causally related to latanoprost therapy using valid scientific methodology. These possible side effects occur rarely. Cystoid macular edema, iritis, and herpes simplex keratitis occur in eyes with risk factors. To scientifically establish a causal relationship between drug therapy and rare side effects, repeated rechallenging with masked controls is required. With rare exception, such methodology has not been used with any of these putative side effects. Nevertheless, even without firm establishment of a causal relationship, caution is advised with the use of prostaglandin analogs in eyes with risk factors for cystoid macular edema, iritis, and herpes simplex keratitis until properly designed, large, controlled studies provide more definitive information.

Effects of enzymatic sterilization detergents on the corneal endothelium.

OBJECTIVE: To evaluate the potential of enzymatic detergents to cause endothelial damage and anterior segment inflammation. METHODS: Paired rabbit corneas were mounted in an in vitro specular microscope. Endothelia were perfused either with the sterile irrigating solution BSS Plus (Alcon Laboratories Inc, Ft Worth, Tex) (control) or 0.1%, 0.4%, or 1.0% Medline Enzymatic Detergent (Medline Industries Inc, Mundelein, Ill) in BSS Plus. Swelling rates were determined by regression analysis. Human endothelia were perfused using 1.56% detergent. All corneas were fixed for scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Endothelial permeability was determined following perfusion of 0.78% detergent. Finally, in vivo intracameral injections with 1.56% or 3.9% detergent were performed to evaluate clinical changes and to correlate with histopathologic analysis. RESULTS: Dose-related corneal swelling rates were observed. Digital specular micrographs revealed greater endothelial cell damage when perfused with 1.0% detergent. The TEM of endothelia exposed to 1.0% solutions demonstrated abnormal vacuolization and dilated extracellular spaces, which manifested as an increased corneal permeability to 3 to 4 times that of controls. Human corneas swelled comparably to rabbit corneas but demonstrated increased sensitivity when evaluated by TEM and SEM. Histopathologic analysis after intracameral injection revealed thickened corneas with fewer endothelial cells and irises with increased inflammatory and fibrinous responses compared with controls. CONCLUSIONS: Medline Enzymatic Detergent causes a dose-dependent corneal swelling, ultrastructural damage, increased corneal permeability, and increased inflammatory response in the iris after intracameral injection. CLINICAL RELEVANCE: Failure to adequately rinse the detergent from surgical instruments may result in corneal edema and intraocular inflammation.

[Acute hypopyon uveitis with rifabutin therapy of systemic Mycobacterium avium complex (MAC) infection in AIDS]. / Akute Hypopyon-Uveitis unter Rifabutin-Therapie einer systemischen Mycobacterium avium complex (MAC)-Infektion bei AIDS.

BACKGROUND: Hypopyon-uveitis has been identified as a dosage-dependent side effect in patients with acquired immunodeficiency syndrome who are treated for Mycobacterium avium complex (MAC) infection with systemic rifabutin. PATIENTS AND METHODS: We report a 38-year-old female AIDS patient with bilateral hypopyon uveitis under therapy with rifabutin in combination with clarithromycin and indinavir. RESULTS: At the time of presentation of the bilateral hypopyon uveitis the patient was treated with rifabutin (300 mg/day), clarithromycin (1000 mg/day) and ethambutol (1000 mg/day) for an M. avium complex infection. Also, the patient received the protease inhibitor indinavir. The rifabutin dose was reduced to 150 mg/day. Hypopyon and inflammation resolved under therapy with steroids. CONCLUSIONS: The concomitant use of rifabutin, clarithromycin, and protease inhibitors may lead to hypopyon uveitis. Reduction of dosage of rifabutin (150 mg/day) and treatment with topical steroids are required.

Iritis associated with intravenous cidofovir.

OBJECTIVE: To report two patients with AIDS and cytomegalovirus retinitis who developed iritis after receiving intravenous cidofovir. Both experienced recurrent symptoms upon rechallenge. CASE SUMMARIES: Two HIV-positive patients with cytomegalovirus retinitis infections previously controlled with intravenous ganciclovir or foscarnet were treated with intravenous cidofovir. Symptoms of iritis developed after the second or third dose of cidofovir. One patient experienced symptoms unilaterally, while the other patient had bilateral symptoms. In both patients, the iritis resolved with topical ophthalmic therapy, but recurred following subsequent infusions of cidofovir. Therapy with cidofovir was discontinued, and no further recurrences of iritis were noted. One patient had post-inflammatory fixed dilated pupils. CONCLUSIONS: Iritis can uncommonly occur in patients receiving intravenous cidofovir and oral probenecid. With prompt drug discontinuation and administration of topical corticosteroids and/or mydriatic agents, symptoms are usually reversible.

[A comparative study of thio-tepa and mitomycin C in the treatment of pterygium. Preliminary results]. / Etude comparative du Thio-tepa et de la Mitomycine C dans le traitement du ptérygion. Résultats préliminaires.

AIMS: To compare the efficacy of Thio-tepa and Mitomycine C to obviate recurrence; to compare cost-efficacy ratios; to evaluate their facility of use and their complications. METHODS: In a prospective blinded study, 36 patients undergoing surgery for 46 primary and recurrent pterygium were assigned randomly to three groups: group 1 received 0.02 mg/ml of Mitomycine C three times daily for 5 days; group 2 received Thio-tepa four times daily for 6 weeks, group 3 served as a control receiving distilled water three times daily for five days. RESULTS: Recurrence rates were 38%, in group 1; 28% in group 2; 82% in group 3 respectively. Follow-up ranged from 15 to 44 weeks (mean 27.93 +/- 8.9 weeks). Mean delay recurrence time was 6.3 weeks. Topical Mitomycin caused: iritis, conjunctival irritation, excessive lacrymation, photophobia, ocular pain; Thio-tepa caused: photophobia, foreign body sensation, headache. CONCLUSIONS: Mitomycine C appears to be an effective and safe adjunctive treatment for this cost-efficacy and this facility of use comparison.

Adverse events and autopsy findings after intravitreous cidofovir (HPMPC) therapy in patients with acquired immune deficiency syndrome (AIDS).

OBJECTIVE: The purpose of the study is to evaluate the adverse events and autopsy findings in a series of consecutive 20-microg intravitreous cidofovir injections at a single institution. DESIGN: The study design was a nonrandomized, consecutive case series. PARTICIPANTS: Seventy-six patients with acquired immune deficiency syndrome with cytomegalovirus retinitis were studied prospectively. Sixty-three patients had 1 month's follow-up or longer, and this comprised the study group. In addition, histopathologic findings from 18 eyes of 9 patients were studied at autopsy. INTERVENTION: A total of 296 injections of 20 microg cidofovir were given in 115 eyes. Sixty-three patients who had 246 injections in 93 eyes had 1 month's follow-up or longer for the evaluation of adverse events. MAIN OUTCOME MEASURES: Postinjection chronic hypotony associated with permanent visual loss, transient hypotony, iritis, and its long-term sequela (posterior synechia and cataract, retinal detachment, extraocular cytomegalovirus involvement) were the outcomes of interest in this study. Additionally, light and electron microscopic studies of human eyes were performed. RESULTS: The most severe adverse event was postinjection chronic hypotony. This phenomenon was associated with permanent visual loss. This was observed in 1% of the injections and 3% of the eyes of the patients (95% confidence interval, 0%-6%). Transient hypotony associated with mild-to-moderate visual loss developed in 14%, but vision recovered to baseline levels in these eyes subsequently. Analysis showed that transient hypotony in the injected eye could predict postinjection chronic hypotony in the fellow eye (two-tailed Fisher's exact test, P = 0.02). The incidence of iritis was 32%; posterior synechia and cataract were the long-term sequela of the iritis and developed in 19% and 11% of the eyes, respectively. The incidence of retinal detachment was lower (6%). Histopathologic evaluation of the eyes showed mild-to-moderate atrophy of the nonpigmented epithelium of the ciliary body and no other evidence of intraocular toxicity. CONCLUSIONS: The most serious adverse event was postinjection chronic hypotony, which occurred in 3% of eyes. Episodes of transient hypotony appear to indicate that the fellow eye was predisposed to chronic hypotony. Therefore, it may be prudent to give intravitreous injections at least 2 weeks apart in the fellow eye to evaluate the clinical response of the injected eye.

Pharmacological evaluation of anti-inflammatory pyrrole-acetic acid derivative eye drops.

The effects of mucoadhesive eye drops containing a pyrrole-acetic acid derivative (tolmetin) at 0.5% concentration on ocular inflammation produced by sodium arachidonate in the rabbit's eye were evaluated. Furthermore, the bioavailability of the mucoadhesive formulation in the aqueous humor against an aqueous-based solution was compared. Tolmetin eye drops significantly reduced the signs of ocular inflammation elicited by sodium arachidonate on conjunctiva and iris. Tolmetin treatment significantly reduced the levels of prostaglandin E2, polymorphonuclear leukocytes and protein concentration in aqueous samples obtained from the eyes treated with arachidonate. The de novo production of prostaglandin E2 by corneas obtained from rabbits sacrificed 2 hours after arachidonate instillation were significantly higher in samples taken from controls than in corneas obtained from the eyes treated with tolmetin eye drops. Furthermore, the drug treatment significantly reduced the rise in intraocular pressure arachidonate-induced. The mucoadhesive formulation showed a higher bioavailability in aqueous humor compared to the aqueous-based solution both in the uninflamed and in the inflamed rabbit eyes.

Iritis and hypotony after treatment with intravenous cidofovir for cytomegalovirus retinitis.

OBJECTIVE: To describe intraocular inflammation due to treatment with intravenous cidofovir dihydrate for cytomegalovirus retinitis. DESIGN: Retrospective cohort. SETTING: Three university outpatient ophthalmology clinics. PATIENTS: All patients treated with intravenous cidofovir therapy before October 31, 1996. INTERVENTION: Treatment with intravenous cidofovir was given according to standardized protocols. Intraocular inflammation was treated according to the best medical judgment. MAIN OUTCOME MEASURES: The presence of new intraocular inflammation, the severity of inflammation, visual acuity, and intraocular pressure. RESULTS: Eleven cases of iritis (26%) occurred among 43 patients. In 6 cases, the iritis was bilateral. Patients who experienced iritis were more likely to have been previously treated for cytomegalovirus retinitis (P = .03), to be diabetic (P = .05), or to be receiving protease inhibitors (P < .001). Four patients and 15 control subjects had also taken rifabutin (P = .70). The onset of iritis occurred at a mean (+/-SD) of 4.9 +/- 1.8 days after a cidofovir dose and after a mean (+/-SD) of 4.2 +/- 1.6 doses of cidofovir. Six eyes of 4 patients had hypotony. Five eyes of 5 patients had a persistent decrease in visual acuity of at least 2 Snellen lines. CONCLUSIONS: Acute intraocular inflammation may occur with or without hypotony after intravenous cidofovir therapy, similar to the reactions seen after intravitreous administration. Although the manifestations may be severe, they are manageable with topical corticosteroid therapy in most cases. Cidofovir therapy can be continued in some patients if medical necessity warrants, but recurrent inflammation or permanent hypotony may occur.