Physicochemical and microbiological stability study of two new preservative-free methylprednisolone eye drops. / Estudio de estabilidad fisicoquímica y microbiológica de 2 nuevos colirios de metilprednisolona sin conservantes.

OBJECTIVE: To study the physicochemical and microbiological stability over 90 days of two preservative-free methylprednisolone sodium succinate (MTPSS) 1 mg/ml and 10 mg/ml eye drops for use in ocular pathologies such as Sjögren's syndrome and dry eye syndrome. METHOD: The two eye drops were prepared from injectable MTPSS (Solu-moderin® and Urbason®), water for injection and normal saline solution. In accordance with ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) guidelines, they were then stored in triplicate under refrigerated conditions (5 ±3 °C), at room temperature (25 ± 2 °C), and at 40 °C (±2 °C). In accordance with the USP (United States Pharmacopeia), physicochemical controls of the active ingredient content were carried out by HPLC-UV (High Performance Liquid Chromatography with Ultraviolet detection), together with controls of pH, osmolality, and visual examination. Microbiological sterility was also tested under refrigerated conditions up to 30 days in open containers and up to 90 days in closed ones. RESULTS: The eye drops stored at 5 °C were the most stable; in the 1 mg/ml eye drops, degradation of the drug fell below 90% from day 21, and in the 10 mg/ml eye drops, from day 42. pH change did not vary by ≥1 unit in formulations stored at 5 °C, unlike the other formulations. Changes in osmolality did not exceed 5% on day 90 in any storage conditions. Samples of non refrigerate eye drops at 10 mg/ml, presented a white precipitate from day 14 and 28 respectively. Non-refrigerated 1 mg/ml eye drops presented suspended particles on day 90. There were no color changes. Microbiological analysis showed that sterility was maintained for over 90 days in the closed containers, although microbial contamination was detected from day 21 in the open containers. CONCLUSIONS: 1 mg/ml MTPSS eye drops show physicochemical and microbiological stability for 21 days under refrigeration, compared to 42 days for 10 mg/ml eye drops stored under the same conditions. However, since they do not include preservatives in their composition, they should not be used for more than 7 days after opening.

Relationship between the number of glaucoma medications, ocular surface disorder, and treatment adherence / Relação entre o número de medicamentos para glaucoma, distúrbio da superfície ocular e adesão ao tratamento

ABSTRACT Purpose: To determine the relationship of ocular surface disease, the number of glaucoma medications prescribed and its influence on treatment adherence. Methods: In this cross-sectional study, demographic data of patients with glaucoma were collected, and patients completed the ocular surface disease index questionnaire and the glaucoma treatment compliance assessment tool. Ocular surface parameters were assessed by "Keratograph 5M." Patients were stratified into two groups according to the amount of prescribed ocular hypotensive eye drops (Group 1, one or two classes of medications; Group 2, three or four classes) Results: In total, 27 eyes of 27 patients with glaucoma were included: 17 using 1 or 2 topical medications (Group 1) and 10 eyes using 3 or 4 classes (Group 2). For the Keratograph assessment, patients using ≥3 medications had significantly smaller tear meniscus height (0.27 ± 0.10 vs. 0.43 ± 0.22; p=0.037). The analysis of Ocular Surface Disease Index questionnaire showed higher scores among the groups using more hypotensive eye drops (18.67 ± 13.53 vs. 38.82 ± 19.72; p=0.004). Regarding the glaucoma treatment compliance assessment tool, Group 2 had worse scores in components of forgetfulness (p=0.027) and barriers due to lack of drops (p=0.031). Conclusion: Patients with glaucoma using more hypotensive eye drops had worse tear meniscus height and ocular surface disease index scores than those using fewer topical medications. Patients using three or four drug classes had worse predictors of glaucoma adherence. Despite worse ocular surface disease results, no significant difference in self-reported side effects was found.

RESUMO Objetivo: Determinar a relação entre doença da superfície ocular (OSD), número de medicamentos prescritos para o glaucoma, e como isso influencia na adesão ao tratamento. Métodos: Neste estudo transversal, pacientes com glaucoma foram submetidos à coleta de dados demográficos, preenchimento do questionário Ocular Surface Disease Index e do Glaucoma Treatment Compliance Assessment Tool. Os parâmetros da superfície ocular foram avaliados pelo "Keratograph 5M". Indivíduos foram estratificados em 2 grupos de acordo com a quantidade de colírios hipotensores oculares prescritos (Grupo 1: uma ou duas classes de medicamentos; Grupo 2: três ou quatro classes). Resultados: No total, 27 olhos de 27 pacientes com glaucoma foram incluídos: 17 usando 1 ou 2 medicamentos tópicos (Grupo 1) e 10 olhos usando 3 ou 4 classes (Grupo 2). Na avaliação do Keratograph, os pacientes em uso de 3 ou mais medicamentos apresentaram altura do menisco lacrimal significativamente menor (0,27 ± 0,10 vs. 0,43 ± 0,22; p=0,037). Análise do questionário OSDI mostrou escores mais altos entre o grupo que usou mais colírios hipotensores (18,67 ± 13,53 vs. 38,82 ± 19,72; p=0,004). Em relação ao Glaucoma Treatment Compliance Assessment Tool, o Grupo 2 apresentou piores escores nos componentes de esquecimento (p=0,027) e barreiras por falta de colírios (p=0,031). Conclusão: O estudo demonstrou que pacientes com glaucoma usando mais colírios hipotensivos apresentaram piores escores de altura do menisco lacrimal e Ocular Surface Disease Index, em comparação com aqueles que usaram menos medicamentos tópicos. Pacientes em uso de 3 ou 4 classes de colírios tiveram piores preditores de adesão ao glaucoma. Apesar dos piores resultados de doença da superfície ocular, não houve diferença significativa nos efeitos colaterais relatados.

Ligneous conjunctivitis: Fresh-frozen plasma and heparin use intra-and postoperatively, a report of two cases

ABSTRACT Ligneous conjunctivitis is a rare chronic form of recurrent membranous inflammation and plasminogen deficiency. Ocular manifestations may be associated with sites other than mucous membranes, such as the oral cavity, internal ear, respiratory, genitals, and kidney. Treatment is extremely difficult because of the lack of topic plasminogen drops, and a high volume is required for systemic supplementation. This report aimed to present two patients with ligneous conjunctivitis treated with membrane excision, topical fresh-frozen plasma, and heparin intra-, and postoperatively. No recurrence was found in the ligneous membrane in the 12-month follow-up. The use of topical fresh-frozen plasma and heparin after membrane excision could be effective to avoid recurrence.

Autologous serum eye drops diluted with 0.5% methylcellulose and 0.9% saline solution: a clinical comparative study / Colírio de soro autólogo diluído com metilcelulose 0,5% e solução salina 0,9%: um estudo clínico comparativo

ABSTRACT Purpose: This clinical study compared autologous serum eye drops diluted with 0.5% methylcellulose and 0.9% saline solution. The subjective criteria for symptom improvement and the objective clinical criteria for response to therapy were evaluated. Methods: This longitudinal prospective study enrolled 23 patients (42 eyes) with persistent epithelial defects or severe dry eye disease refractory to conventional therapy who had been using autologous serum 20% prepared with methylcellulose for > 6 months and started on autologous serum diluted in 0.9% saline solution. The control and intervention groups consisted of the same patients under alternate treatments. The subjective criteria for symptom relief were evaluated using the Salisbury Eye Evaluation Questionnaire. The objective clinical criteria were evaluated through a slit-lamp examination of the ocular surface, tear breakup time, corneal fluorescein staining, Schirmer's test, rose Bengal test, and tear meniscus height. These criteria were evaluated before the diluent was changed and after 30, 90, and 180 days. Results: In total, 42 eyes were analyzed before and after 6 months using autologous serum diluted with 0.9% saline. No significant differences were found in the subjective criteria, tear breakup time, tear meniscus, corneal fluorescein staining, or rose Bengal test. Schirmer's test scores significantly worsened at 30 and 90 days (p=0.008). No complications or adverse effects were observed. Conclusions: This study reinforces the use of autologous serum 20% as a successful treatment for severe dry eye disease resistant to conventional therapy. Autologous serum in 0.9% saline was not inferior to the methylcellulose formulation and is much more cost-effective.

RESUMO Objetivo: Este estudo comparou o colírio de soro au tólogo manipulado com metilcelulose a 0,5% com solução salina 0,9%. Critérios subjetivos de melhora dos sintomas e critérios clínicos objetivos para resposta à terapia foram avaliados. Métodos: Este estudo prospectivo longitudinal envolveu 23 pacientes (42 olhos) com defeitos epiteliais persistentes ou doença de olho seco grave refratária à terapia convencional que usavam colírio de soro autólogo 20% preparado com metilcelulose por mais de 6 meses e iniciaram soro autólogo diluído em solução salina 0,9%. Os grupos controle e intervenção consistiam dos mesmos pacientes sob tratamentos alternados. Os critérios subjetivos para o alívio dos sintomas foram avaliados usando o Salisbury Eye Evaluation Questionnaire. Os critérios objetivos foram avaliados por meio de exame em lâmpada de fenda incluindo: tempo de ruptura da lágrima, coloração da córnea com fluoresceína, teste de Schirmer, coloração com rosa bengala e altura do menisco lacrimal. Esses critérios foram avaliados antes da troca do diluente e após 30, 90 e 180 dias. Resultados: Um total de 42 olhos foram analisados antes e após 6 meses usando soro autólogo diluído com solução salina 0,9%. Nenhuma diferença significativa foi encontrada nos critérios subjetivos, tempo de ruptura da lágrima, menisco lacrimal, coloração com fluoresceína ou rosa bengala. Os resultados dos testes de Schirmer pioraram significativamente em 30 e 90 dias (p=0,008). Não foram observadas complicações ou efeitos adversos. Conclusões: Este estudo reforça o uso do colírio de soro autólogo 20% como um tratamento de sucesso para a doença do olho seco grave resistente à terapia convencional. O soro autólogo diluído em solução salina a 0,9% não foi inferior à formulação de metilcelulose.

2% Ganciclovir Controlled Posner-Schlossman Syndrome Relapse and Reduced the Chance of Corticosteroid Dependence: A Large Cohort in East China.

PURPOSE: To present the process from acute Posner-Schlossman syndrome (PSS) relapse to remission under 2% ganciclovir (GCV), corticosteroids and anti-glaucoma agents on 323 patients. METHODS: A retrospective study enrolling 323 PSS patients. Demographics and ophthalmic examination results were generated. Patients were treated with GCV, corticosteroids and anti-glaucoma agents andfollowed up every 2-6 weeks. RESULTS: Patients were divided into the GCV monotherapy (N = 65, 20.12%), GCV and corticosteroids (G+C, N = 106) and GCV, corticosteroid and IOP-lowering drugs (G+C+L, N = 152) group. The G+C+L group had the highest intraocular pressure (IOP, 26.33 ± 10.26 mmHg, P < 0.001) and largest cup-to-disc ratio (0.58 ± 0.19, P < 0.05). After treatment, IOP of three groups dropped to similar level. Ninety-nine (30.65%) patients were corticosteroid-dependent whose daily corticosteroid consumption decreased after using GCV (from 2.23 ± 1.02 to 0.97 ± 0.98 drops/day). CONCLUSION: 2% GCV solutions worked effectively on PSS relapse with corticosteroids and anti-glaucoma agents. In patients suspected of CMV infection, proper GCV could reduce the chance of corticosteroid dependence.

Effects of Brimonidine, Omidenepag Isopropyl, and Ripasudil Ophthalmic Solutions to Protect against H2O2-Induced Oxidative Stress in Human Trabecular Meshwork Cells.

PURPOSE: We investigated whether hydrogen peroxide (H2O2)-induced oxidative stress causes human trabecular meshwork (HTM) cell dysfunction observed in open angle glaucoma (OAG) in vitro, and the effects of topical glaucoma medications on oxidative stress in HTM cells. METHODS: We used commercially available ophthalmic solutions of brimonidine, omidenepag isopropyl, and ripasudil in the study. HTM cells were exposed to H2O2 for 1 h, with or without glaucoma medications. We assessed cell viability and senescence via WST-1 and senescence-associated-ß-galactosidase (SA-ß-Gal) activity assays. After exposure to H2O2 and glaucoma medications, we evaluated changes in markers of fibrosis and stress by using real-time quantitative polymerase chain reaction (qPCR) to measure the mRNA levels of collagen type I alpha 1 chain (COL1A1), fibronectin, alpha-smooth muscle actin (α-SMA), matrix metalloproteinase-2 (MMP-2), endoplasmic reticulum stress markers of C/EBP homologous protein (CHOP), 78-kDa glucose-regulated protein (GRP78), and splicing X-box binding protein-1 (sXBP-1). RESULTS: HTM cell viability decreased and SA-ß-Gal activity increased significantly after exposure to H2O2. Treatment with three ophthalmic solutions attenuated these changes. Real-time qPCR revealed that H2O2 upregulated the mRNA levels of COL1A1, fibronectin, α-SMA, CHOP, GRP78, and sXBP-1, whereas it downregulated MMP-2 mRNA expression significantly. Brimonidine suppressed the upregulation of stress markers CHOP and GRP78. Additionally, omidenepag isopropyl and ripasudil decreased the upregulation of COL1A1 and sXBP-1. Furthermore, ripasudil significantly suppressed fibrotic markers fibronectin and α-SMA, compared with the other two medications. CONCLUSION: In vitro, H2O2 treatment of HTM cells induced characteristic changes of OAG, such as fibrosis changes and the upregulation of stress markers. These glaucomatous changes were attenuated by additional treatments with brimonidine, omidenepag isopropyl, and ripasudil ophthalmic solutions.

Points to consider when developing drugs for dry eye syndrome.

Changes in both the social environment (e.g., the increased use of electronic media) and the atmospheric environment (e.g., air pollution and dust) have contributed to an increasing incidence of eye disease and an increased need for eye care. Notably, the signs and symptoms of dry eye syndrome can impact the daily quality of life for various age groups, including the elderly, and usually requires active treatment. The symptoms of dry eye syndrome include tear film instability, hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities. As treatments for dry eye are being developed, a standardized guideline is needed to increase the efficiency of drug development and improve the quality of clinical trial data. In this paper, we present general considerations for the pharmaceutical industry and clinical trial investigators designing clinical trials focused on the development of drugs to treat dry eye syndrome.

Estabilidad del colirio de insulina para el tratamiento de úlceras corneales refractarias / Stability of insulin eye drops in the treatment of refractory corneal ulcers

Objetivo: Determinar y comparar la estabilidad físico-química y microbiológica de dos colirios de insulina 25 UI/ml elaborados con suerofisiológico o balanced salt solution bajo diferentes condiciones de conservación durante 120 días.Método: Los colirios se elaboraron por triplicado con insulina Actrapid®100 Ul/ml y balanced salt solution o suero fisiológico como vehículo, yfueron conservados a temperatura ambiente (25 °C), en nevera (2-8 °C)o congelador (–20 °C) durante 120 días. Se determinó la concentraciónde insulina mediante cromatografía liquida de ultra alta resolución, laosmolalidad y el pH a días 0, 3, 7, 15, 30, 60, 90 y 120. Asimismo, seextrajeron muestras para estudios microbiológicos en los días 0, 15, 30,60, 90 y 120.Resultados: La formulación elaborada con suero fisiológico mantuvola concentración de insulina por encima del 90% con respecto a la inicialtras 120 días de estudio en todas las condiciones de temperatura. En elcaso del colirio elaborado con balanced salt solution, la concentraciónse mantuvo estable en ambiente y congelador tras 120 días, aunque ennevera descendió por debajo del 90% a día 90 de estudio. Los valoresde osmolalidad y pH se mantuvieron constantes en ambas formulacionesy condiciones de conservación. No se observó crecimiento microbiológico en ninguna de las muestras retiradas.Conclusiones: El colirio de insulina 25 UI/ml elaborado con suerofisiológico es estable 120 días, conservado tanto a temperatura ambientecomo en nevera o congelador, protegido de la luz. Con balanced saltsolution permanece estable 120 días a temperatura ambiente y congelador, reduciéndose el periodo de validez a 90 días en el caso de laconservación en nevera. (AU)

Objective: To determine and compare the physicochemical and microbiological stability of two 25 IU/mL insulin eye drop formulations madewith normal saline and a balanced salt solution, respectively, stored for120 days under various conditions.Method: Eye drops were compounded in triplicate with 100 IU/mLActrapid® insulin and either normal saline or a balanced salt solution asvehicles, and they were stored alternatively at room temperature (25 °C),in a refrigerator (2-8 °C) or in a freezer (–20 °C) for 120 days. Insulinconcentrations were determined by ultra-high resolution liquid chromatography, and osmolality and pH values were measured at days 0, 3, 7,15, 30, 60, 90 and 120. Likewise, samples were extracted for microbiological studies on days 0, 30, 60, 90 and 120.Results: The formulation made with normal saline maintained insulinconcentrations above 90% of the baseline level after 120 days acrossall temperature conditions. In the case of the balanced salt solution-basedeye drops, insulin concentration when stored at room temperature or inthe freezer remained stable after 120 days, although insulin concentrationwhen stored in the refrigerator fell below 90% on day 90 of the study.Osmolality and pH values remained constant in both formulations andacross all storage conditions. No microbiological growth was observedin any of the samples. Conclusions: 25 IU/mL insulin eye drops made with normal salineremain stable for 120 days whether they are stored at room temperature,in a refrigerator or in a freezer, provided that they are protected fromlight. When made with a balanced salt solution, they remain stable for120 days at room temperature and in a freezer, their shelf life being reduced to 90 days in the case of storage in a refrigerator. (AU)

Ophthalmic Solutions with a Broad Antiviral Action: Evaluation of Their Potential against Ocular Herpetic Infections.

HSV-1 can be associated with severe and recurrent eye infections characterized by a strong inflammatory response that leads to blepharoconjunctivitis, epithelial and stromal keratitis, and retinal necrosis. The incidence of HSV-1 keratitis is 1.5 million every year worldwide, including more than 40,000 new cases exhibiting serious visual failures. Generally, the therapy uses antiviral drugs to promote healing; however, there are currently no compounds that are able to completely eradicate the virus. In addition, the phenomenon of resistance is rapidly spreading among HSV-1 strains, creating mutants developing resistance to the common antiviral drugs; therefore, deep research on this issue is warranted. The efficacy of different ophthalmic solutions already on the market was evaluated for reducing HSV-1 infection. Different plaque assays were set up on epithelial cells, revealing that two ophthalmic solutions were able to inhibit viral replication in the early stages of infection. The data were further confirmed by molecular tests analyzing the expression levels of the principal genes involved in HSV-1 infection, and a strong reduction was observed after only 1 min of eye-drop treatment. Collectively, these results suggested the use of ophthalmic solutions as potential antiviral options for the treatment of ocular herpetic infection.

2% Ganciclovir Eye Drops Control Posner-Schlossman Syndrome Relapses With/Without Cytomegalovirus Intraocular Reactivation.

Background: To observe and compare the efficacy of 2% ganciclovir eye drops in the treatment of Posner-Schlossman Syndrome relapses with/without cytomegalovirus intraocular reactivation. Methods: A prospective cohort study enrolling 101 patients diagnosed unilateral Posner-Schlossman Syndrome in Eye & ENT hospital, Fudan University, Shanghai, China. Thorough ophthalmic examinations were given. Aqueous humor sample was collected from the attacked eye of each patient and all pathogen immunoglobulins tests were performed. All patients were treated with appropriate corticosteroids and intraocular pressure-lowering drugs. 2% ganciclovir eye drops were given to patients whose cytomegalovirus antibody aqueous humor/serum correction ratio >0. Patients were followed up for 2 months. Ocular manifestations and cumulative drug dose were recorded. Results: A cytomegalovirus ratio >0.40 was considered cytomegalovirus reactivation. The reactivation group (N = 46) had significantly higher percent of iris depigmentation (78.26%, P < 0.05) and endothelial cell loss rate (19.46%, P < 0.001) than the latent group (N = 55, 58.18% and 10.86%, respectively). The cumulative treatment time and 2% ganciclovir doses were 6.50 ± 4.67 weeks and 181.70 ± 130.95 drops for the reactivation group; 5.95 ± 4.11 weeks and 161.89 ± 110.66 drops for the latent group (P > 0.05). The median cumulative 2% ganciclovir estimated for inflammation control were 252.00 ± 50.71 and 224.00 ± 32.45 drops for the reactivation and latent group. The residual rate of uncontrolled cases was 0.19 ± 0.15 and 0.00, respectively (P < 0.05). Conclusions: A treatment course of 8-9 weeks' 2% ganciclovir is recommended to relapses both with and without cytomegalovirus intraocular reactivation. Preventive ganciclovir application may benefit patients with historical cytomegalovirus infections. Clinical Trial Registration: www.chictr.org.cn, identifier: ChiCTR1900022340, Date: 2019/04/06.

In search of disambiguation: development of eye drop bottle sleeves to aid in identification and survey among possible users. A cross-sectional study

BACKGROUND: Considerable numbers of individuals present low vision, blindness, illiteracy and other conditions that could possibly impair their identification of medications, such as eye drops. Through helping these individuals to identify their eye drops, they can achieve greater autonomy. Misidentification can be avoided through use of multisensory sleeves that can be adapted to most eye drop bottles. Correct use of eye drops is important for preventing progression of diseases like glaucoma that could potentially lead to blindness. OBJECTIVE: To develop bottle sleeves to aid in identification of eye drops and then interview a group of possible users to evaluate the acceptance of the solution. DESIGN AND SETTING: Cross-sectional survey performed at an ophthalmological clinic in São Paulo (SP), Brazil. METHODS: We describe the development of multisensory sleeves to assist in identification of eye drops. To assess the acceptance of this solution, we interviewed 18 patients who were currently using three or more types of eye drops. RESULTS: We developed four prototypes for eye drop bottle sleeves and conducted an acceptance test on them. Most of the patients who answered the survey about the sleeves were elderly. Most (95%) reported believing that the sleeves would help reduce the risk of mixing up eye drops with other medications that also dispense drops. They also believed that these would increase their autonomy in using eye drops. CONCLUSION: The solution presented was well accepted and may help increase safety in using eye drops through preventing misidentification.

Amniotic membrane extract eye drops: a new approach to severe ocular surface pathologies.

A protocol for processing amniotic membrane as an extract to be re-hydrated and administered topically as eye drops (amniotic membrane extract eye drops, AMEED) has been developed. Safety and efficacy of AMEED was assessed in patients with severe ocular surface pathologies. prospective clinical follow-up of ocular surface symptoms before and after regular application of the AMEED for at least 4 weeks on patients with severe ocular surface disorders as chronic dry eye disease, limbal stem cell deficiency, neurotrophic ulcer and permanent and disabling symptomatology that were refractory to conventional treatment. Efficacy and tolerability were assessed based on patient-reported symptoms, objective measurements, and reports of adverse events. Thirty-six eyes from 25 patients were included. Although the visual quality function score, by means of a VQF25 questionnaire, was not statistically different after the treatment (p = 0.4657), there was a clear trend, statistically significant, towards the improvement in ocular symptoms like foreign body sensation, itching and stinging (p < 0.05) and clinical presentation of the pathology. All patients with corneal ulcer showed complete epithelization. Topically applied AMEED proved to be safe, well tolerated and effective in reducing the symptoms and clinical signs of severe ocular disease. Further studies are needed to confirm the best indications for AMEED use.

Antiangiogenic Nanomicelles for the Topical Delivery of Aflibercept to Treat Retinal Neovascular Disease.

The traditional intravitreal injection delivery of antivascular endothelial growth factor (anti-VEGF) to the posterior segment of the eye for treatment of retinal diseases is invasive and associated with sight-threatening complications. To avoid such complications, there has been significant interest in developing polymers for topical drug delivery to the retina. This study reports a nanomicelle drug delivery system made of a copolymer EPC (nEPCs), which is capable of delivering aflibercept to the posterior segment topically through corneal-scleral routes. EPC is composed of poly(ethylene glycol) (PEG), poly(propylene glycol) (PPG), and polycaprolactone (PCL) segments. In this study, aflibercept-loaded nEPCs (nEPCs + A) are capable of penetrating the cornea in ex vivo porcine eye models and deliver a clinically significant amount of aflibercept to the retina in laser-induced choroidal neovascularization (CNV) murine models, causing CNV regression. nEPCs + A also demonstrate biocompatibility in vitro and in vivo. Interestingly, this study also suggests that nEPCs have intrinsic antiangiogenic properties. The ability to deliver anti-VEGF drugs and the intrinsic antiangiogenic properties of nEPCs may result in synergistic effects, which can be harnessed for effective therapeutics. nEPCs may be a promising topical anti-VEGF delivery platform for the treatment of retinal diseases.

Focusing on antioxidant treatment of dry eye and novel drug study / 中华实验眼科杂志

Dry eye is becoming more common worldwide.Its pathophysiology is complicated, and its condition is chronic.Treatment options of dry eye are ineffective.As a multifactorial ocular surface disease, tear film instability, tear hyperosmolarity, ocular surface inflammation, and neurosensory abnormalities resulted from various causes are main natural pathological processes of dry eye.This multifactorial process of the disease leads to poor efficacy of single anti-inflammatory therapy.Oxidative stress is closely related to the occurrence of dry eye.During the decrease of tear film stability, reactive oxygen species produced by oxidative stress system damage the myelin sheath of ocular nerve and the lipid layer of tear film, inducing or aggravating the ocular inflammatory response.Targeting the main causes of dry eye's pathogenesis, stopping the vicious cycle of inflammatory responses in each link, and relieving patients' conditions are the main goals of antioxidant therapy.The development of anti-inflammatory and antioxidant medications is currently the main focus of international research on novel anti-dry eye medications.Some progresses have been made in the area of targeting oxidative stress biomarkers, mitochondrial targeting medications, mucin secretion, antioxidant enzymes like glycoprotein selenium and lactoferritin, as well as multifunctional nanoagents, and the antioxidant eye drops using nanomaterials have more advantages.Antioxidant treatment may be one of the potential future avenues of dry eye clinical research.Ophthalmologists and researchers should be fully aware of, pay close attention to and actively participate in investigations that are relevant to dry eye antioxidant therapy and the development of new medications.

Mass variability in drops of multidose eyedrops: a quality and reliability study / Variabilidade da massa das gotas dos colírios: um estudo de qualidade e confiabilidade

ABSTRACT Purpose: This quality and reliability study aimed to identify the mass variability of multidose eyedrops and to verify the existence of a reference pattern for the drop volume of eyedrops using standard lubricant eyedrops available on the Brazilian market. Methods: Five brands of lubricant eyedrops were evaluated. An ideal standard 20 µL drop of eyedrops from each manufacturer was captured using an adjustable micropipette. The eyedrop bottles were randomly selected, and five measurements of the samples' masses were collected using calibrated precision scales. Results: The mass of the 20 µL samples varied significantly (p<0.001) among the different manufacturers. However, among eyedrops of the same brand, mass variation was not statistically different. The global mean mass of all weighed drops was 18.24 mg, and non-uniformity was identified across all eyedrop brands. Conclusion: Significant variations in the drop masses of common lubricant eyedrops were identified using standard laboratory equipment. Heterogeneity in the drop volume of standard eyedrop medications suggest that potential dosage discrepancies exist, possibly altering treatment efficacy. A pre-established reference measure may lead to the production of more appropriately sized eyedrops for use in human eyes.

RESUMO Objetivo: Este estudo de qualidade e confiabilidade teve como objetivo identificar a variabilidade da massa do volume da gota de colírios multidose e verificar a existência de um padrão de referência para o volume da gota dos colírios usando lágrimas artificiais do mercado brasileiro. Métodos: Cinco marcas de colírios lubrificantes foram avaliadas quanto ao volume da gota. Uma gota padrão ideal de 20 µL de cada fabricante foi coletada usando uma micropipeta ajustável. Os frascos dos colírios foram selecionados aleatoriamente e cinco medidas das massas das amostras foram coletadas usando escalas de precisão calibradas. Resultados: A massa das amostras de 20 µL variou significativamente (p<0,001) entre os diferentes fabricantes. No entanto, entre os colírios da mesma marca, a variação da massa não foi estatisticamente diferente. A massa média global de todas as gotas pesadas foi de 18,24 mg e foi observada uma não-uniformidade entre todas as marcas de colírios. Conclusão: Identificou-se uma variação significativa nas massas do volume das gotas dos colírios lubrificantes, usando equipamento padrão de laboratório. A heterogeneidade no volume da gota dos colírios testados sugere a existência de discrepâncias potenciais em suas posologias, possivelmente alterando a eficácia do tratamento. Uma medida de referência pré-estabelecida pode levar à produção de colírios com gotas de tamanho mais apropriado para uso em olhos humanos.

Inhibitory Effect of Ophthalmic Solutions against SARS-CoV-2: A Preventive Action to Block the Viral Transmission?

In 2020, a global pandemic was declared following the spread of SARS-CoV-2, the pathogen responsible for COVID-19. The risk of infection is high due to the ease of transmission, which can occur orally, through droplets, or via contact with contaminated surfaces and objects. It has also been demonstrated that the ocular surface can constitute a transmission route, especially in hospital settings, where health care workers can become a dangerous source of infection. In order to increase prevention and reduce the spread of the virus on the ocular surface, the antiviral activity of already-marketed eye drops against SARS-CoV-2 was evaluated. Iodim, Ozodrop, Septavis, and Dropsept were tested against SARS-CoV-2 in plaque-assay experiments at different stimulation times. Furthermore, the expression levels of early and late genes were evaluated through molecular assays. Results indicated that three of the four ophthalmic solutions showed a considerable dose-dependent inhibition of viral replication, highlighting their use as potential antiviral drugs against SARS-CoV-2 and preventing other ocular infections.

Presión intraocular preoperatoria en el control del cierre angular primario tratado con extracción del cristalino / Preoperative intraocular pressure for the control of primary angle closure treated with clear lens extraction

Introducción: la extracción del cristalino transparente en pacientes con cierre angular primario se plantea si existe presión intraocular mayor o igual que 30 mm Hg o daño por glaucoma. En ojos con elevación moderada de la presión intraocular se desconocen los resultados. Objetivo: evaluar la influencia de la presión intraocular preoperatoria en el control del cierre angular primario tratado con extracción del cristalino transparente. Material y Métodos: se realizó un estudio pre-experimental, entre enero de 2013 y enero de 2020, incluyó 78 ojos de 78 pacientes con cierre angular primario tratados con extracción del cristalino transparente; divididos en dos grupos según presión intraocular preoperatoria. Para el análisis estadístico se empleó chi cuadrado de independencia, probabilidad exacta de Fisher, prueba t para muestras independientes y análisis de varianza de medidas repetidas; con significación estadística del 95 por ciento. Resultados: hubo diferencias significativas entre ambos grupos para longitud axial (p=0,003), grosor del cristalino (p<0,001) y espesor corneal central (p=0,016). La presión intraocular y número de colirios, variaron de forma muy significativa (p<0,001) entre el pre y posoperatorio, y entre ambos grupos en los diferentes momentos analizados. En el grupo A el 94,4 por ciento de los ojos mostró control absoluto posoperatorio invariable en el tiempo, en el grupo B la mayoría de los ojos tuvo control relativo con diferencias muy significativas (p<0,001) entre ambos. Conclusiones: la presión intraocular preoperatoria influye en el control del cierre angular primario tratado con extracción del cristalino transparente; valores previos menores que 30 mm Hg, propician mejor control posoperatorio(AU)

Introduction: Clear lens extraction is considered in patients older than 50 years with primary angle closure and intraocular pressure greater than or equal to 30 mm Hg or damage due to glaucoma. The results are unknown in eyes with a moderate elevation of intraocular pressure. Objective: To evaluate the influence of preoperative intraocular pressure in the control of the primary angle closure treated with clear lens extraction. Material and Methods: A pre-experimental study was conducted between January 2013 and January 2020. It included a total of 78 eyes of 78 patients with primary angle closure treated with clear lens extraction. They were divided into two groups according to preoperative intraocular pressure. For statistical analysis, Chi-square test, Fisher's exact probability test, and t test were used for independent samples and analysis of variance with repeated measurements; with 95 percent statistical significance. Results: There were significant differences in axial length (p=0,003), lens thickness (p<0,001) and central corneal thickness (p=0,016) between both groups. Intraocular pressure and the number of eye drops varied very significantly (p<0,001) between the pre-and postoperative periods and between both groups at the different moments analyzed. In group A, 94,4 percent of the eyes showed absolute postoperative control, which remained unchanged over time. In group B, most eyes had relative control. There were very significant differences (p<0,001) between both groups. Conclusions: Preoperative intraocular pressure influences the control of primary angle closure treated with clear lens extraction; previous values less than 30 mm Hg favor better postoperative control(AU)

Effect of steroid eyedrops after trabeculectomy in glaucoma patients: a keratograph analysis / Efeito de colirios esteróides pré-operatório em pacientes com glaucoma: análise com keratograph

ABSTRACT Purpose: To investigate the use of preoperative steroid eyedrops in glaucoma patients undergoing trabeculectomy for ocular surface disease. Methods: A total of 31 eyes of 31 glaucoma patients were included. Only glaucoma patients who had been using at least three topical intraocular pressure-lowering medications for longer than 6 months were included. All patients were treated with loteprednol etabonate ophthalmic suspension 0.5% four times per day for 1 week before trabeculectomy. Data from baseline (day of surgery) and the follow-up visit (2 weeks after surgery) were included. All patients underwent a detailed ophthalmologic examination. Ocular surface disease was evaluated using the Ocular Surface Disease Index questionnaire and clinical measures, including tear breakup time, conjunctival hyperemia, and biomicroscopy to detect the presence or absence of keratitis. Ocular Surface Disease Index scores greater than 13 indicated a clinically relevant presence of ocular surface disease. In addition, all patients underwent keratograph analysis. The comparison of ocular surface disease before and after trabeculectomy was assessed using a paired test. Results: The mean age of the glaucoma patients was 69.90 ± 10.77 years. The average visual acuity was 0.40 ± 0.34 logMAR. The overall Ocular Surface Disease Index prevalence rate was 27.20 ± 17.56 units. Clinical assessment revealed no significant difference in bulbar redness, breakup time, or keratitis before and after surgery (p>0.05 for all comparisons). Keratograph analysis showed that the only two parameters that were significantly different before and after trabeculectomy ewere the bulbar redness by keratograph (BR-K) and the average noninvasive tear breakup time. Patients presented more conjunctival hyperemia and shorter noninvasive tear breakup time after trabeculectomy as compared with before surgery (p=0.013 and p=0.041, respectively). Conclusions: The present study not only confirms the high prevalence of clinical findings of ocular surface disease in glaucoma patients but also reveals new objective parameters measured by keratograph analysis. Apart from using loteprednol etabonate ophthalmic suspension 0.5% 1 week before the surgery, our sample presented a worsening of conjunctival hyperemia (bulbar redness by keratograph) and also a shorter noninvasive tear breakup time postoperatively.

RESUMO Objetivo: Investigar a ação de colírios esteróides na doença de superfície ocular em pacientes a serem submetidos a cirurgia de trabeculectomia. Métodos: Foram incluídos 31 olhos de 31 pacientes com glaucoma em uso de pelo menos 3 medicações tópicas anti- hipertensivas há mais de 6 meses. Todos os pacientes foram tratados com colírio de etabonato de loteprednol 0,5% (1 gota a cada 6 horas) durante os 7 dias precedentes à cirurgia de trabeculectomia. Além disso, foram submetidos a exame oftalmológico completo e responderam questionário validado que visa avaliar parâmetros subjetivos correlacionados a doenças da superfície ocular (Ocular Surface Disease Index). Os aspectos clínicos avaliados foram: tempo de ruptura lacrimal, coloração da córnea após colírio de fluoresceína (ceratite) e hiperemia conjuntival. Os pacientes foram, ainda, submetidos à análise da superfície ocular através de novo software tecnológico denominado "Keratographic", tecnologia não invasiva que permite avaliar a doença da superfície ocular. A comparação da doença de superfície ocular antes e após a trabeculectomia foi avaliada estatisticamente através do teste pareado. Resultados: A média de idade dos participantes foi de 69,90 ± 10,77 anos. A AV média foi de 0,40 ± 0,34 logMAR. A taxa de prevalência global da Ocular Surface Disease Index foi de 27,20 ± 17,56 unidades. Em relação à avaliação clínica, não houve diferença significativa em relação hiperemia, ruptura lacrimal e ceratite antes e após a cirurgia (p>0,05 para todas as comparações). Em relação à análise com o "keratograph (menisco lacrimal, hiperemia, tempo de ruptura do filme lacrimal, meibografia para a pálpebra superior e inferior), os dois únicos parâmetros que diferiram significativamente antes e após a trabeculectomia, foram hiperemia e a média do tempo de rupture do filme lacrimal. Após a cirurgia de trabeculectomia, os pacientes apresentaram aumento da hiperemia conjuntival e diminuição do tempo de ruptura do filme lacrimal (p=0,013 e p=0,041, respectivamente). Conclusões: O presente estudo, não somente confirma a elevada prevalência da doença de superfície ocular em pacientes com glaucoma, como também demonstra que a mesma pode ser mensurada objetivamente através de parâmetros mensurados pelo Keratograph. Apesar de ter utilizado etabonato de loteprednol 0,5% uma semana antes da cirurgia, nossa amostra apresentou piora da hiperemia conjuntival e diminuição no tempo de ruptura do filme lacrimal no pós-operatório.

Recalcitrant Pseudomonas Aeruginosa Keratitis with Hyphaema.

PURPOSE: To report a case of recalcitrant pseudomonas keratitis with a rare presentation of hyphaema. OBSERVATION: A 45-year-old female was noted to have contact lens-related pseudomonas keratitis with hyphaema. The organism was refractory to multiple antibiotics and only responded to Tazocin eye drops. CONCLUSION AND IMPORTANCE: Hyphaema is a rare presentation in bacterial keratitis and could represent infection with an especially virulent organism. Use of Aspirin could precipitate hyphaema in infective keratitis. Alternative antibiotic choices such as Tazocin, colistin, meropenem, and imipenem can be considered when standard therapy is ineffective for multidrug-resistant Pseudomonas keratitis.

Medical Costs of and Changes in Glaucoma Treatment among Patients Newly Starting Glaucoma Care.

Purpose: To use a medical claim database to investigate medical costs and treatment patterns among patients newly starting glaucoma care.Subjects and methods: Subjects registered in the Japan Medical Database Center (JMDC) from January 2005 to March 2016 who were newly diagnosed with glaucoma, started glaucoma treatment, and had treatment records covering more than five years were included in the analysis. All direct medical costs were collected for a period of up to ten years. Factors affecting medical costs were analyzed. Changes in hypotensive eyedrops and choices related to glaucoma surgery were also analyzed.Results: Out of approximately 1.42 million subjects, 2,393 satisfied the inclusion and exclusion criteria. The average total medical cost incurred per patient over a period of ten years was US$9,030, including US$1,214 during the initial year. The proportion of the total cost represented by the cost of hypotensive eyedrops increased from 5.2% to 10.6% over the ten-year period. Medical costs were higher in patients younger than ten years old than in patients of all other age groups. The number of ocular hypotensive eyedrops increased from 0.9 to 1.5 over the ten-year period. Medical costs were higher for subjects with secondary glaucoma than for other subjects. Sixty-three patients underwent trabeculotomy or trabeculectomy, and trabeculectomy was the preferred choice in later years.Conclusions: The total direct medical cost associated with glaucoma was US$9,030 for the first ten years. Drug costs gradually increased with treatment duration and patient age and varied by glaucoma type.