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.

[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.

Anterior nongranulomatous uveitis after intravitreal HPMPC (cidofovir) for the treatment of cytomegalovirus retinitis. Analysis and prevention.

BACKGROUND AND OBJECTIVE: The authors characterize and analyze the incidence of a previously reported mild anterior nongranulomatous uveitis associated with intravitreal injections of (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC), also termed cidofovir (Vistide, Gilead Sciences, Foster City, CA). This is an acyclic nucleoside phosphonate analogue with a potent anticytomegalovirus effect. The authors also analyzed the effects of probenecid therapy, as well as prophylaxis with probenecid plus topical corticosteroids and cycloplegics on the course and outcome of the uveitis. METHODS: Prospective case series from a tertiary referral center, which included 46 consecutive patients with acquired immune deficiency syndrome (AIDS) and cytomegalovirus (CMV) retinitis. There was a total of 130 injections in 69 eyes treated with 20 micrograms of intravitreal HPMPC. Forty-one patients (119 injections) received oral probenecid, 5 patients (11 injections) did not, and 21 patients (53 injections) received topical corticosteroids and cycloplegics as an adjuvant to probenecid in the prophylaxis of iritis. RESULTS: Mild to moderate nongranulomatous iritis was seen in 26% of patients after their first injection (n = 12). Patients receiving probenecid prophylaxis after first injection had a significantly lower frequency of iritis versus patients who did not receive probenecid at the time of first injection (P = 0.0089). In contrast, treatment with topical corticosteroid and cycloplegics after injection did not statistically significantly affect the frequency of iritis in patients (P = 0.44). The development of iritis after a second injection of HPMPC was more likely if it had occurred after the initial injection (P = 0.015; Fisher's exact test). All cases of iritis were treated with topical corticosteroids and cycloplegics, and there was no permanent impairment of vision secondary to iritis after HPMPC injection in any eyes. CONCLUSIONS: Anterior uveitis was seen in 26% of patients after first-time HPMPC injection. Concomitant use of probenecid appears to decrease the frequency of the iritis from 71% to 18% in patients with AIDS and CMV retinitis after the first intravitreal injection of HPMPC. Topical corticosteroid administration after injection (before iritis) was ineffective in preventing iritis treatment with topical corticosteroids and cycloplegics resulted in resolution of all iritis cases.

Acute iritis induced by granulocyte colony-stimulating factor used for mobilization in a volunteer unrelated peripheral blood progenitor cell donor.

We describe a volunteer unrelated peripheral blood progenitor cell donor with previously diagnosed dermatitis herpetiformis in whom the administration of G-CSF for the mobilization of precursor cells induced acute iritis. G-CSF has been administered to healthy people with minimal side-effects but when used in patients with autoimmune disorders worsening of symptoms or new manifestations may be a potential concern.

Metipranolol-associated granulomatous iritis.

PURPOSE: Topical metipranolol therapy for primary open-angle glaucoma has been associated with anterior granulomatous uveitis in the United Kingdom. We studied granulomatous uveitis reactions to topical metipranolol 0.3% therapy for primary open-angle glaucoma in two patients in the United States. METHODS: Two patients, aged 71 and 81 years, were given topical metipranolol 0.3% therapy for primary open-angle glaucoma. RESULTS: Both developed granulomatous uveitis. The iritis was associated with an increase in intraocular pressure in both patients and resolved on discontinuation of the drug. One patient was inadvertently rechallenged with metipranolol, and the iritis recurred. CONCLUSIONS: Topical metipranolol 0.3% therapy may be associated with the development of granulomatous uveitis and a paradoxical increase in intraocular pressure.

Serious complications of topical mitomycin-C after pterygium surgery.

BACKGROUND: The use of topical mitomycin (mitomycin-C) as a medical adjunct to pterygium and glaucoma surgery is increasing. METHODS: The authors report on a series of 10 patients who experienced serious, vision-threatening complications associated with the use of this drug after pterygium surgery. RESULTS: Complications included severe secondary glaucoma (4 patients), corneal edema (3 patients), corneal perforation (1 patient), corectopia (2 patients), iritis (8 patients), sudden onset mature cataract (2 patients), scleral calcification (1 patient) and incapacitating photophobia and pain (8 patients). Two patients required penetrating keratoplasties and a third required three lamellar keratoplasties. Another patient underwent four additional surgeries including a conjunctival Z-plasty, scleral patch grafting, and conjunctival autografting before his intractable pain and photophobia resolved 15 months after the original surgery. Because of these complications, 6 patients required a total of 20 return visits to the operating room after their original pterygium surgery. In 5 eyes, visual acuity remained at 20/200 or less. Three of the six patients with the most severe complications had concomitant chronic external diseases (rosacea [3 patients], ichthyosis [1 patient], keratitis sicca [1 patient]). CONCLUSION: The authors urge extreme caution in the use of mitomycin. If mitomycin is used, the lowest possible concentration should be applied for the shortest time period in an effort to avoid these complications. A prospective multicenter study of the ophthalmic use of this medication is needed.

Acute granulomatous iritis following 5 fluorouracil therapy for failed trabeculectomy.

We are reporting a case which developed idiosyncratic anterior granulomatous uveitis following a single dose of subconjunctival 5 Fluorouracil. This has not been previously reported anywhere in the world.

Fibrinous iritis due to oxybuprocaine.

Following minor surgery performed under topical application of oxybuprocaine (Dorsacaine, Novesin) two patients suffered from fibrinous iritis and moderate corneal swelling. We believe that this represents a toxic reaction caused by an inadvertent entry of this drug into the anterior chamber during the procedure.

Intraocular inflammation of denatured viscoelastic substance in cases of cataract extraction and lens implantation.

I present three successive pseudophakic cases that had intraocular inflammation (iritis) and bullous keratopathy presumably caused by denatured sodium hyaluronate (Healon). The denatured Healon was injected into the anterior chamber mixed with fresh Healon during routine planned extracapsular cataract extraction and intraocular lens implantation, when the cannula was reused after sterilization by disinfectants and autoclaving. A residuum of the viscoelastic substance remained inside the cannula and its nature was changed to a toxic chemical by the action of disinfectants and the sterilization procedures. The first two cases developed pseudophakic bullous keratopathy and had successful penetrating keratoplasties performed. The third case had minimal intraocular inflammation. The hypothesis that this intraocular reaction was due to denatured Healon was confirmed by use of a rabbit eye model. I recommend using a single-use disposable cannula for intracameral administration of Healon.

[Acute granulomatous interstitial nephritis with iritis. Possible induction by non-steroidal antiphlogistics]. / Akute granulomatöse interstitielle Nephritis mit Iritis. Mögliche Auslösung durch nicht-steroidale Antiphlogistika.

A 49-year old woman developed non-oliguric acute renal failure accompanied by bilateral acute anterior uveitis, following a three weeks' period of lethargy, anorexia and temporary fever. Kidney biopsy revealed acute interstitial nephritis with interstitial infiltrations of lymphocytes and monocytes, as well as multiple perivascular epithelioid granulomas. A substantial improvement of renal function was achieved under treatment with systemic corticosteroids. The uveitis resolved completely under additional topical treatment. During a follow-up period of 9 months, there has been no relapse of nephritis or uveitis. The disease of this patient resembles the so-called TINU syndrome of unknown aetiology. Remarkable features of the present case are the histological diagnosis of granulomatous acute interstitial nephritis in the absence of systemic granulomatous disease, as well as a possible association with the administration of non-steroidal antiinflammatory drugs.

Migration of acetylated hemicellulose from capillary hemodialyzer to blood, causing scleritis and/or iritis.

From November 1981 to early March 1982, an outbreak of scleritis and/or iritis occurred among patients treated with a Nipro brand NAC series cellulose acetate capillary dialyzer. The rate of incidence with dialyzers produced in 1982 was significantly higher than that with dialyzers produced in 1981. An extract obtained from the dialyzers caused iritis in rabbits after its infusion into an auricula vein. Glycerol, acetylated carbohydrate (AC) derivatives, urethane derivatives, and polypropyleneglycol were found in the extract. AC derivatives caused iritis in rabbits, whereas they caused hyperemia of the bulbar conjunctiva in dogs. The AC derivatives contained xylose and glucose units in a ratio of 1.6-2.3:1. The amounts of AC derivatives were significantly larger in the extracts from 1982 than from 1981 devices. Moreover, another brand, but the same type, of dialyzer, the Cordis Dow 4000, contained a slight amount of them. These facts show that AC derivatives derived from hemicellulose played a primary role in the outbreak.

Intraocular irritation evaluation of benzalkonium chloride in rabbits.

The purpose of this study was to define the threshold for intraocular irritation of benzalkonium chloride, a preservative used in some formulations which enter the anterior segment of the eye during ocular surgery. Various concentrations of benzalkonium were injected into anterior chambers of albino rabbit eyes. Conjunctivitis, flare, iritis, and corneal changes occurred in a dose response pattern. The threshold of irritation was 0.03%, with highest nonirritating concentration being 0.01%. In other works in this laboratory, threshold of irritation for topical ocular benzalkonium was 0.05%, but the nature of ocular changes was less substantial than those observed intraocularly. Because the threshold for intraocular irritation is less than that topically, the nature of ocular changes was different for two routes, and there is a paucity of clinical data for intraocular benzalkonium chloride, a safety factor of 10 was utilized in setting the highest safe concentration of 0.001% for intraocular use. The preservative efficacy of 0.001% is questionable; therefore, we cannot endorse benzalkonium chloride as a preservative for formulations which will enter the anterior segment of the eye.