Ophthalmic Corticosteroids Research Articles

Development and Validation of Claims-Based Algorithms for Conjunctivitis and Keratitis.

Ocular surface disorders have been reported among patients with various medical conditions, including atopic dermatitis (AD). Nonetheless, validated algorithms to identify conjunctivitis and keratitis in claims data are lacking. Develop validated, claims-based algorithms for conjunctivitis and keratitis among patients with AD using medical records. Patients with AD were identified in a claims database between March 2017 and November 2019. Among these patients, candidate algorithms were developed that included diagnosis codes for conjunctivitis or keratitis, alone and in combination with ophthalmic treatments. Among patients who met ≥ 1 candidate algorithms, a subset was randomly selected for medical record review. Additionally, records from a random sample of patients with AD were reviewed to assess sensitivity. Overall, 341 records were sought and 262 adjudicated by an expert ophthalmologist. The positive predictive value (PPV) of each algorithm was calculated and compared to a pre-specified threshold of ≥ 70%. For conjunctivitis, the final algorithm was ≥ 1 conjunctivitis diagnosis (PPV = 81%, 95% confidence interval [CI]: 73%-87%). For keratitis, the final algorithm combined the following 2 candidate algorithms: ≥ 1 keratitis diagnosis and ≥ 1 dispensing of a topical antibiotic or antibiotic-steroid combination (PPV = 91%); and ≥ 1 keratitis diagnosis and ≥ 1 dispensing of an ophthalmic corticosteroid, topical immune-modulator, or topical NSAID (PPV = 68%) for an overall PPV of 80% (95% CI: 55%-93%). The first claims-based algorithms to identify conjunctivitis and keratitis among AD patients were developed and validated. They are available for use in future studies, particularly to better understand conjunctivitis and keratitis occurrence among patients with AD.

Diamond burr debridement of calcific band keratopathy in 24 eyes of 22 horses.

To evaluate the safety and effectiveness of diamond burr debridement (DBD) for the treatment of calcific band keratopathy (CBK) in horses. Medical records from horses with CBK were reviewed over a period of 4 years. Diagnosis of CBK was based on slit-lamp examination findings, and DBD was performed on standing sedated horses. Follow-up was obtained by clinical reevaluation of the treated eyes or a telephone survey with the referring veterinarian. Twenty-two horses of different ages (median: 11 years; range: 5-23) representing 24 CBK-affected eyes (14 left eyes and 10 right eyes) were included in the study. The patients had a medical history of chronic and recurrent uveitis, which required repeated long-term treatments with various combinations of ophthalmic corticosteroids. DBD alone cleared the cornea in 22 affected eyes (92%), but it was combined with blade scraping in two cases with thick calcium plaques. The postoperative medication included a topical antibiotic, atropine drops, and oral flunixin meglumine. Corneal healing was achieved in 21 eyes (87%), 5-21 days (median time 13 days) postoperatively. The three remaining horses were lost to follow-up. Recurrence occurred in 5 of the 21 (24%) reexamined eyes, 3-12.5 weeks (median 8 weeks) postoperatively, and required a second DBD. Four of the 21 eyes ended up being enucleated due to sequelae of uveitis. The main limitations of the study include those inherent to all retrospective clinical data collections. Mechanical DBD can readily and safely clear the cornea in horses with CBK, but recurrence of calcium deposition is possible.

Development of Crystalline Corneal Opacities (Steroid Keratopathy) in Dogs After Treatment With Ophthalmic Corticosteroids.

To retrospectively evaluate and describe the relationship between the use of topical corticosteroids and the development of crystalline corneal opacities (steroid keratopathy) in a colony of research Beagles and Beagle-derived dogs. Medical records of 73 purpose-bred Beagles and Beagle-derived dogs were reviewed from June 2012 to May 2021. All dogs were treated with topical ophthalmic corticosteroids for at least 21 days. In addition to regular ophthalmic examination, some dogs also had a systemic lipid profile (n = 6) performed to work up further and characterize the crystalline corneal opacities. Globes of 3 dogs were examined histopathologically. Axial stromal crystalline corneal opacities were appreciated in 25 eyes of 14 dogs after a median of 141 days after initiating treatment (35-396 days). Multiple corticosteroids were used, including neomycin-polymyxin b-dexamethasone 0.1% ophthalmic ointment, prednisolone acetate 1% ophthalmic suspension, and difluprednate 0.05% ophthalmic emulsion (Durezol). Resolution of corneal opacity was documented in 4 of 25 eyes when ophthalmic corticosteroids were discontinued after a median of 406.5 days (271-416 days). Histopathologic examination revealed a dense band of acellular material, poorly staining with periodic acid-Schiff, subtending the corneal epithelium, and being surrounded by spindle cells. This case series documents the onset of steroid keratopathy in Beagles and Beagle-derived dogs after treatment with ophthalmic corticosteroids. Clinical resolution of steroid keratopathy lesions may be possible after discontinuation of ophthalmic corticosteroids.

Localized alopecia and suppression of hypothalamic-pituitary-adrenal (HPA) axis in dogs following treatment with difluprednate 0.05% ophthalmic emulsion (Durezol\xae)

BackgroundDespite the common use of topical ophthalmic corticosteroids in dogs, detailed reports on systemic and dermatologic adverse effects are limited.ResultsNine purpose-bred research Beagles were treated with difluprednate 0.05% ophthalmic emulsion in one or both eyes 2–3 times daily. Some difluprednate treated dogs developed mild to severe alopecia of the periocular region, face, and distal pinna (5/9). The median duration of treatment prior to onset of dermatologic signs for difluprednate treated dogs was 550 days (453–1160 days). Diagnostic testing included complete blood count (CBC) and serum biochemistry, adrenocorticotropic hormone (ACTH) stimulation testing combined with endogenous ACTH measurement, and skin biopsy. The CBC and chemistry were within normal limits for all dogs. There were varying degrees of suppression of the hypothalamic-pituitary-adrenocortical (HPA) axis with difluprednate treatment. Dogs with the most profound alopecic changes had less pronounced HPA axis suppression compared to dogs with no integumentary changes. Skin biopsies demonstrated follicular atrophy and follicular keratosis. When topical difluprednate was reduced to unilateral therapy, the hair regrew on the untreated side of the face. In addition to the affected research dogs, a 7-year old female spayed Chihuahua that was being treated as a clinical patient with long-term difluprednate 0.05% ophthalmic emulsion developed generalized hypotrichosis on the head and body and a potbellied appearance. ACTH stimulation testing revealed suppression of the HPA axis with a mild increase in serum alkaline phosphatase (ALP) activity and a urine specific gravity of 1.016. The combination of clinical signs and laboratory abnormalities was supportive of iatrogenic hyperadrenocorticism.ConclusionsIn dogs long-term use of difluprednate ophthalmic emulsion results in HPA axis suppression and in some cases iatrogenic hyperadrenocorticism. A novel pattern of localized alopecia is suspected to be related to dermal absorption and local action due to superior potency and penetration compared to other commonly utilized ophthalmic corticosteroids.

Severe pseudomembranous keratoconjunctivitis with deterioration of eyesight induced by immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) play a significant role in therapy for relapsed or refractory cancers due to their excellent efficacy. ICIs, however, frequently induce immune-related adverse events (irAEs) in various tissues and organs, sometimes leading to severe conditions. Thus, early identification and treatment of irAEs are important. Herein, the authors report two cases of a rare type of irAE, severe keratoconjunctivitis with deterioration of eyesight, induced by ICIs. Characteristically, both cases were accompanied by concurrent severe oral mucositis. The patients were treated successfully with both systemic and topical ophthalmic corticosteroids, resulting in complete remission of severe pseudomembranous conjunctivitis and full recovery of eyesight. ICI-induced keratoconjunctivitis progresses rapidly and can lead to blindness. Thus, prompt diagnosis and treatment are necessary.

Temporal Association between Topical Ophthalmic Corticosteroid and the Risk of Central Serous Chorioretinopathy.

This retrospective, nationwide, matched cohort study investigated the temporal relationship of central serous chorioretinopathy (CSCR) following topical ophthalmic corticosteroid (TOC) use. Using the Longitudinal Health Insurance Database 2000 (LHID2000), we collected patients diagnosed with CSCR between January 2001 and December 2010 (n = 2921) and a control group (n = 17,526). Information for each patient was collected and tracked from the index date until December 2011. TOC users were classified based on (i) the date of the last prescription before diagnosis: current users (≤30 days) and former users (31–182 days and ≥183 days) and (ii) the prescription refill intervals: persistent users (interval ≤90 days) and non-persistent users (interval >90 days). The odds ratio (OR) was estimated from multivariate conditional logistic regression after adjusting for relevant confounders. After adjusting for age, sex, geographic region, index date, previously known comorbidities, the date of last TOC prescription before diagnosis, or prescription refilling intervals, the results revealed that patients were likely to have developed CSCR while using TOCs currently (OR = 30.42, 95% CI = 25.95–35.66, p < 0.001) and persistently (OR = 7.30, 95% CI = 6.13–8.69, p < 0.001) as compared to the controls. Our results indicate that current or persistent TOCs use increases the risk of CSCR. Thus, patients requiring TOCs should be advised of this risk, particularly in current or persistent use conditions.

Corticosteroids in ophthalmology: drug delivery innovations, pharmacology, clinical applications, and future perspectives.

Corticosteroids remain the mainstay of the treatment for various ocular conditions affecting the ocular surface, anterior and posterior segments of the eye due to their anti-inflammatory, anti-oedematous, and anti-neovascularization properties. Prednisolone, prednisolone acetate, dexamethasone, triamcinolone acetonide, fluocinolone acetonide, and loteprednol etabonate are amongst the most widely used ophthalmic corticosteroids. Corticosteroids differ in their activity and potency in the eye due to their inherent pharmacological and pharmaceutical differences. Different routes and regimens are available for ocular administration of corticosteroids. Conventional topical application to the eye is the route of choice when targeting diseases affecting the ocular surface and anterior segment, while periocular, intravitreal, and suprachoroidal injections can be potentially effective for posterior segment diseases. Corticosteroid-induced intraocular pressure elevation and cataract formation remain the most significant local risks following topical as well as systemic corticosteroid administration. Invasive drug administration via intracameral, subconjunctival, and intravitreal injection can enhance ocular bioavailability and minimize dose and dosing frequency of administration, yet may exacerbate ocular side effects of corticosteroids. This review provides a critical appraisal of the ophthalmic uses of corticosteroid, routes of administration, drug delivery fundamentals and novel ocular implantable steroid delivery systems, factors influencing side effects, and future perspectives for ocular corticosteroid therapy.

Ophthalmic Corticosteroids in Pregnant Women with Allergic Conjunctivitis and Adverse Neonatal Outcomes: Propensity Score Analyses

The risks of topical ophthalmic corticosteroids during pregnancy remain unclear. This study investigated the association between exposure to topical ophthalmic corticosteroids during pregnancy and adverse neonatal outcomes. Retrospective, cohort, database study. Pregnant women with allergic conjunctivitis in the JMDC claims database (JMDC, Tokyo, Japan) between 2005 and 2018 were included. Adverse neonatal outcomes (congenital anomalies [CA], preterm birth [PB], low birthweight [LB], and the composite of these 3 outcomes) were compared between mothers who did and did not receive topical ophthalmic corticosteroids during the first trimester. Controls were women who were not prescribed topical ophthalmic corticosteroids during the first trimester. First, propensity scores were calculated with known confounders, including disorders during pregnancy, other chronic comorbidities, and use of antihistamines. Logistic regression was then conducted with propensity score adjustment. A total of 6,847 eligible women were identified of whom 898 (13%) had received topical ophthalmic corticosteroids. CA occurred in 5.5% and 4.9%, respectively; PB in 3.4% and 3.9%, respectively; LB in 5.9% and 7.0%, respectively; and the composite outcome in 11.7% and 11.7% of unexposed and exposed mothers, respectively. Corticosteroid eye drops were not significantly associated with an increase in CA (adjusted odds ratio [aOR], 0.78; 95% confidence interval [CI], 0.54-1.14; P= .20); PB (aOR, 1.23; 95% CI, 0.80-1.88; P= .35); LB (aOR, 1.17; 95% CI, 0.84-1.61; P= .35), or composite outcome (aOR, 0.95; 95% CI, 0.73-1.22; P= .68). The use of topical ophthalmic corticosteroids in pregnant women with allergic conjunctivitis was not associated with any increase in CA, PB, or LB.

Loteprednol Etabonate (Submicron) Ophthalmic Gel 0.38%: A Review in Post-Operative Inflammation and Pain Following Ocular Surgery.

Loteprednol etabonate ophthalmic gel 0.38% (Lotemax® SM; hereafter referred to as loteprednol etabonate gel 0.38%) is a topical ophthalmic corticosteroid approved in the USA for the treatment of post-operative inflammation and pain following ocular surgery. This formulation provides improved drug delivery compared with loteprednol etabonate micronized gel 0.5%, with a smaller drug particle size (in the submicron range) to improve dissolution and penetration into ocular tissues, meaning less loteprednol etabonate is required to exert therapeutic effect. In two multicentre, randomized phase III trials, significantly more loteprednol etabonate gel 0.38% than vehicle recipients displayed complete resolution of ocular inflammation and ocular pain at day 8 post cataract surgery. Complete resolution of pain was seen as early as post-operative day 3. Treatment-related ocular adverse events in the loteprednol etabonate gel 0.38% group occurred in < 1% of subjects and included one incidence each of photophobia, cystoid macular oedema, eyelid oedema and instillation site pain. Treatment with loteprednol etabonate gel 0.38% had no meaningful impact on intraocular pressure (IOP) or visual acuity. Thus, loteprednol etabonate gel 0.38% extends the treatment options available in resolving post-operative inflammation and pain in patients who have undergone ocular surgery.

Conjunctivitis in dupilumab clinical trials.

SummaryBackgroundDupilumab blocks the shared receptor component for interleukin (IL)‐4 and IL‐13. It is approved in the U.S.A. for patients aged ≥ 12 years with moderate‐to‐severe atopic dermatitis (AD) uncontrolled by topical prescription medicines or who cannot use topical medicines, for patients in Japan whose AD is uncontrolled with existing therapies, for patients with moderate‐to‐severe AD in Europe who are candidates for systemic therapy and for patients aged ≥ 12 years for maintenance treatment of moderate‐to‐severe asthma uncontrolled with their current medicines. AD trials have reported increased incidence of conjunctivitis for dupilumab vs. placebo.ObjectivesTo characterize further the occurrence and risk factors of conjunctivitis in dupilumab clinical trials.MethodsWe evaluated randomized placebo‐controlled trials of dupilumab in AD (n = 2629), asthma (n = 2876), chronic rhinosinusitis with nasal polyps (CRSwNP) (n = 60) and eosinophilic oesophagitis (EoE) (n = 47).ResultsIn most AD trials, dupilumab‐treated patients had higher conjunctivitis incidence than placebo controls. Higher baseline AD severity and previous history of conjunctivitis were associated with increased conjunctivitis incidence. Conjunctivitis was mostly mild to moderate. Most cases recovered or resolved during the treatment period; two patients permanently discontinued dupilumab due to conjunctivitis or keratitis. Common treatments included ophthalmic corticosteroids, antibiotics, and antihistamines or mast cell stabilizers. Most cases were diagnosed by the investigators. In asthma and CRSwNP trials, the incidence of conjunctivitis was lower for both dupilumab and placebo than in AD trials; dupilumab did not increase the incidence compared with placebo. In the EoE trial, no patients had conjunctivitis.ConclusionsConjunctivitis was more frequent with dupilumab treatment in most AD trials. In dupilumab trials in other type 2 diseases, incidence of conjunctivitis was overall very low, and was similar for dupilumab and placebo. In AD, the incidence of conjunctivitis was associated with AD severity and prior history of conjunctivitis. The aetiology and treatment of conjunctivitis in dupilumab‐treated patients require further study. What's already known about this topic? Ocular disorders, including allergic conjunctivitis, are common in patients with atopic dermatitis (AD).In most dupilumab AD trials, dupilumab‐treated patients had higher conjunctivitis incidence than those receiving placebo.Most cases were mild to moderate and recovered or were recovering during study treatment; study treatment discontinuation due to conjunctivitis was rare.Conjunctivitis incidence was very low and similar for dupilumab and placebo in clinical trials in asthma, chronic rhinosinusitis with nasal polyps and eosinophilic oesophagitis. What does this study add? This analysis confirms and extends the results of the individual clinical trials.Baseline disease‐related factors, including AD severity, prior conjunctivitis history and certain biomarkers (thymus and activation‐regulated chemokine, IgE, eosinophils), were associated with increased incidence of conjunctivitis.Patients who responded well to dupilumab had reduced incidence of conjunctivitis.Further study is needed to elucidate the aetiology and treatment of conjunctivitis in dupilumab‐treated patients with AD.

Use of Topical Steroids in Conjunctivitis: A Review of the Evidence.

Conjunctivitis, or inflammation of the conjunctiva, is a common condition that can be caused by infectious (eg, bacterial or viral infections) and noninfectious (eg, allergy) etiologies. Treatment involves diagnosis of the underlying cause and use of appropriate therapies. A broad-spectrum therapy that can address multiple etiologies, and also the accompanying inflammation, would be very useful. In this review, we discuss the usefulness of topical ophthalmic corticosteroids and ophthalmic formulations that combine corticosteroids with anti-infectives/antibiotics for treating acute infectious conjunctivitis. A review of the published literature and relevant treatment guidelines. Topical corticosteroids are useful in treating ocular inflammation, but most treatment guidelines recommend steroid use generally in severe cases of conjunctivitis. This is partly due to risks associated with steroid use. These risks include potential for prolonging adenoviral infections and potentiating/worsening herpes simplex virus infections, increased intraocular pressure, glaucoma, and cataracts. Most of these perceived risks are not, however, supported by high-quality clinical data. They are also associated with long-term steroid uses that are dissimilar to applications for infectious conjunctivitis. Clinical data show that ophthalmic formulations that combine corticosteroids with broad-spectrum anti-infectives could be effective and well tolerated when used for short-term treatment (≤2 weeks). Corticosteroids, in combination with anti-infectives, could be a promising treatment option for acute conjunctivitis subject to development of further evidence on their effectiveness and safety in conjunctivitis treatment.

Bioequivalence Study Methods with Pharmacokinetic Endpoints for Topical Ophthalmic Corticosteroid Suspensions and Effects of Subject Demographics.

To establish bioequivalence for topical ophthalmic corticosteroid suspensions, some of U.S. product-specific guidances (PSGs) for generic drug products recommend evaluation of aqueous humor (AH) pharmacokinetics (PK). However, the AH PK study is complex because the relationships among AH PK, subject demographics, ocular anatomy, physiology and the compounds' physicochemical characteristics are not well understood. The objective of this research is to provide an overview of the in vivo human AH studies submitted to the U.S. Food and Drug Administration (FDA) for ophthalmic corticosteroid suspensions and to investigate the impact of subject demographics on the human AH PK. We summarized demographic data, sampling time points, sample size per time point and PK parameters to investigate correlations in the studies submitted to the FDA. In the evaluation of subject-specific covariates, the area under the concentration-time curves (AUC) and maximum concentrations (Cmax) were significantly different among ethnicities and age groups. Gender was not primarily associated with differences in AH PK. Our results suggest that the difference in ethnicity and age of the study population play an important role in the AH PK profiles of topical ophthalmic corticosteroid suspensions. Considering the subject-specific covariate effects in designing bioequivalence studies with AH PK endpoints could reduce bias from covariate imbalance and help identify true effects of formulation differences.

Ocular toxocariasis caused by toxocara canis in an adult woman. Case report

Introducción. La toxocariasis es una zoonosis producida por las larvas de los nematodos Toxocara canis y Toxocara cati, parásitos intestinales de los cánidos y los félidos, respectivamente.Presentación del caso. Paciente femenino de 22 años de edad, procedente de Caquetá, Colombia, con un cuadro de 3 meses de evolución con pérdida de visión en ojo izquierdo, acompañada de dolor ocular, diplopía, fotofobia y ojo rojo bilateral, quien presenta desprendimiento de retina en ojo izquierdo diagnosticado por ecografía. La mujer asiste a oftalmología, donde se hace diagnóstico diferencial con retinoblastoma y pars planitis. Se inicia manejo sintomático con corticoides orales y tópicos, con mejoría de la sintomatología, pero persistencia de pérdida de la agudeza visual.Discusión. Al revisar historial de antecedentes socioeconómicos, la paciente convive con perros y gatos, por lo que se piensa en toxocariasis ocular. En el cuadro hemático se observa ligera leucocitosis y linfocitosis, sin eosinofilia. La determinación de anticuerpos anti-Toxoplasma gondii y anti-cisticerco de Taenia solium resultaron negativas, al igual que el VDRL. El test de ELISA para T. canis fue positivo, con unos títulos IgG de 1:64 (positivo ≥1:32, especificidad &gt;90%). Se inicia manejo con corticoide oftálmico, sistémico, albendazol y vitrectomía. Con la intervención quirúrgica se libera banda vítrea, logrando la desaparición de la diplopía, pero persiste granuloma periférico residual, el cual será intervenido por oftalmología.Conclusiones. Dada la posibilidad de ser confundida con un retinoblastoma —una neoplasia maligna que puede requerir la enucleación del ojo—, el conocimiento de esta forma de presentación de la toxocariasis es de suma importancia para los clínicos.

Abstract LB-201: Durable remission of lethal canine hemangiosarcoma

Abstract Background: Angiosarcoma is an uncommon but deadly malignant neoplasm of the vascular endothelium. Primary disease may present at any vascularized site but often occurs in the dermis on the neck and scalp or in the radiation field of women previously-treated for breast cancer. Metastases are often present at first diagnosis, and five-year survival is an abysmal 10-30%. In contrast to the relative paucity of human diagnoses, angiosarcoma is a major killer in the companion canine population, responsible for an estimated 120,000 deaths per year in the United States. The canine disease (termed HSA) closely mimics the human disease in both pathology and genetics. It frequently presents in the dog as acute hemoabdomen secondary to splenic rupture. Even if life-saving splenectomy is performed, median OS is a scant 48 days, and one-year OS hovers at 0%. Given the lack of an analogous rodent model and the accelerated timeline of the canine disease, the outbred companion canine is an ideal system in which to translate novel therapeutic approaches. Here we report an interim analysis of a phase I multi-site, open-label veterinary trial of chemo-immunotherapy performed on consecutively-presenting splenectomized companion canines with histopathologically-verified HSA. Methods: In addition to two cycles of 20 mg/m2 (low-dose) doxorubicin, enrolled study subjects received an autologous cell-therapy reported to generate durable CD8+ memory similar to that of physiologic viral infection. Vaccine was generated from mobilized peripheral blood and cryopreserved tumor antigen and was administered in four doses given in conjunction with type I interferon. Disease burden was monitored monthly by abdominal ultrasound, chest x-ray, and echocardiogram. Results: At the time of abstract submission, median OS had not yet been reached in the per protocol population, with 75% of animals alive and healthy (NED or ongoing PR) at up to one year post-splenectomy (p&amp;lt;0.0002). Abdominal ultrasound documented the resolution of local mesenteric disease in one animal, sternal lymphadenopathy in another, and hepatic metastases in a third. In the intent-to-treat population, median OS was 109 days with 43% of animals alive and healthy at up to one year post-splenectomy. A single incidence of grade 1/2 uveitis resolved promptly with administration of ophthalmic corticosteroids. Conclusions: Administration of autologous cell therapy in conjunction with low-dose doxorubicin is feasible, safe, and highly efficacious in the companion canine population. Generally, if subjects survived long enough to begin treatment, the prognosis became quite favorable. The results suggest that additional clinical studies in both canines and humans are warranted. Citation Format: Matthew M. Halpert, Vanaja Konduri, Yunyu Chen, Dan Liang, Jonathan M. Levitt, Brittany Neal, Caleb Hudson, Heidi Hottinger, Sindy Piscoya, Nicola Wilson, Lisa DiBernardi, Shonda Stallings, Zharkyn Omarbekov, Lori Seelhof, Oscar Ramirez, Qizhi C. Yao, Ratan D. Bhardwaj, Vinod Ravi, Laurel Douglass, William K. Decker. Durable remission of lethal canine hemangiosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-201. doi:10.1158/1538-7445.AM2017-LB-201

Опыт применения трехкомпонентного слезозаменителя Стиллавита® в профилактике комбинированного синдрома «сухого глаза» после катарактальной хирургии

Purpose: to study the possibilities of the three-component substitute for tears (Stillavit®) in the prevention of combined dry eye syndrome after cataract surgery. Material and methods. 60 patients (60 eyes) aged 55 to 82 (ave. 69.7 ± 7.5 years) with subclinical dry eye syndrome of various genesis were operated for cataract. The patients were divided into two clinical groups depending on the type of post-surgical therapy; the main group of 30 patients (30 eyes) who received standard treatment (ophthalmic corticosteroid and antibacterial drugs 4 times a day) and lacrimal replacement therapy with Stilavit® 4 times a day for 7 days, and the control group of 30 patients (30 eyes) who only received standard postoperative treatment for 7 days. Examination setting included biomicroscopу with vital dyes, a Schirmer test, a Norn test, an evaluation of the lacrimal meniscus index, and the degree of epitheliopathy of the conjunctiva and the cornea. Results. Patients with subclinical dry eye syndrome who received corneal surgery with cataract phacoemulsification and IOL implantation are at risk of a complication of the course of dry eye syndrome and the development of a combined dry eye syndrome. Inclusion of the Stilavit® instillation in the early postoperative period 4 times a day for 7 days significantly increases the stability of the pregroovy tear film and lessens the degree of the epitheliopathy of the conjunctiva and the cornea. Conclusions. Based on the examination data, we can recommend a three-component substitute for tears (Stilavit®) for the prevention of the development of combined dry eye syndrome after cataract surgery. For citations: Shurygina I.P., Akulov S.N., Kabardina E.V., et al. A three-component substitute for tears (Stillavit®) in the prevention of combined dry eye syndrome after cataract surgery: usage experience. Russian ophthalmological journal. 2017; 10 (4): 82-8. doi: 10.21516/2072-0076-2017-10-4-82-88 (In Russian).

Impact of the Topical Ophthalmic Corticosteroid Loteprednol Etabonate on Intraocular Pressure.

Corticosteroids are a mainstay therapeutic option for the treatment of ocular inflammation. However, safety remains a concern for clinicians, particularly with long-term use. Though highly effective at suppressing inflammatory and allergic responses, topical ophthalmic corticosteroids carry an inherent risk of side effects, including elevated intraocular pressure (IOP), a risk factor for the development of glaucoma. The corticosteroid loteprednol etabonate (LE) contains an ester rather than a ketone at the C-20 position, minimizing the potential for side effects, including IOP elevation. In early pivotal clinical trials of LE ophthalmic suspension for conjunctivitis (allergic, giant papillary), anterior uveitis, and post-operative inflammation, LE had minimal impact on IOP over short-term (<28 days) and long-term (≥28 days) use. Since then, new LE formulations—including a gel, an ointment, and a suspension of LE in combination with tobramycin—have become commercially available. Multiple studies evaluating the safety and efficacy of LE for inflammatory conditions have been reported, including those requiring longer-term treatment such as photorefractive keratectomy, corneal transplantation, and dry eye disease. We review the available published data on the effect of LE on IOP and report on the cumulative incidence of clinically significant IOP elevations (≥10 mm Hg from baseline) with short-term and long-term LE use. In all studies, LE consistently demonstrated a low propensity to elevate IOP, regardless of formulation, dosage regimen, or treatment duration, including in known steroid responders. The cumulative proportion of patients exhibiting clinically significant IOP increases was 0.8% (14/1725 subjects) in studies evaluating short-term LE treatment and 1.5% (21/1386 subjects) in long-term studies. Furthermore, use of LE was associated with significantly lower rates of IOP elevation ≥10 mm Hg as compared to prednisolone acetate or dexamethasone (when used in combination with tobramycin). The cumulative data to date substantiates a favorable IOP-safety profile for LE with both short-term and long-term use.

A Successful Treatment of Anterior nodular Scleritis with Topical Corticosteroids in a patient with Crohn's Colitis

Scleritis is a chronic, painful, potentially blinding disorder that may also involve the cornea, the adjacent episclera and the unveil tract. It is often associated with ocular complications (corneal changes, glaucoma, cataracts) and in up to 50% of patients it is accompanied by an underlying systemic illness such as rheumatoid arthritis , Wegener’s granulomatosis or inflammatory bowel diseases (IBDs). It is considered to be a relatively rare extra-intestinal ocular manifestation of IBDs (about 2%). This case report represents an anterior nodular scleritis in a patient with Crohn’s colitis who had been primarily treated with topical ophthalmic corticosteroids, and was on infliximab therapy for the underlying disease for three years. Treating a mild form of scleritis with topical corticosteroids could be a reasonable therapeutic option for patients receiving an anti-TNF agent for subjacent inflammatory bowel disease, in order to avoid further immunosuppression with systemic anti-inflammatory drugs.

Associations Between Topical Ophthalmic Corticosteroids and Central Serous Chorioretinopathy: A Taiwanese Population-Based Study.

To investigate the association between central serous chorioretinopathy (CSCR) and topical ophthalmic corticosteroid use. Data were collected from the Longitudinal Health Insurance Database 2000, containing randomly selected medical claim data from 23 million residents in Taiwan. The study cohort comprised all patients diagnosed with CSCR between January 2001 and December 2010 (n = 2921) with a control group of patients (n = 17,526) matched to study patients according to age, sex, geographic region, and date of index medical care. Demographic characteristics, comorbidities, and corticosteroid use (topical ophthalmic, oral, nasal spray, injected, and inhaled) within 1 year before CSCR diagnosis were examined using univariate logistic regression. Student's t-test was used for continuous variables. Adjusted logistic regression was used to compare the odds ratio (OR) of the prognosis of CSCR patients with that of controls. In CSCR patients, we observed an increased prevalence of topical ophthalmic corticosteroid use (OR 6.328, 95% confidence interval [CI] 5.786-6.921, P < 0.0001). After adjusting for age, sex, geographic location of the patient's residence, hypertension, diabetes mellitus, hyperlipidemia, chronic renal disease, peptic ulcer, psychiatric disease, allergic respiratory disease, coronary artery disease, and corticosteroid use, conditional logistic regression analysis showed that CSCR patients were more likely to have used topical ophthalmic corticosteroids recently than the controls (OR 6.036, 95% CI 5.512-6.610, P < 0.0001). Results strongly support an association between recent topical ophthalmic corticosteroid use and CSCR. Thus, patients who require ophthalmic corticosteroids should be advised of the associated risk of developing CSCR.

Seasonal and perennial allergic conjunctivitis.

Seasonal and perennial allergic conjunctivitis are IgE-mediated, hypersensitivity conditions characterized by ocular pruritus, epiphora, and hyperemia. Proper diagnosis is usually made clinically based on history and physical examination. Diagnostic procedures are rarely necessary. Non-pharmacological measures, such as environmental modification and proper eye care, should be considered for all patients with allergic conjunctivitis. Pharmacological interventions may also be required. Milder cases can be treated with short-term topical ophthalmic therapy such as a decongestant/ antihistamine combination, a mast cell stabilizer, or a multi-action agent. Moderate to severe cases may require longer usage of the above agents and/or the addition of an oral antihistamine. Refractory cases may necessitate the use of topical ophthalmic corticosteroids and topical NSAIDs. Immunotherapy, whether via the subcutaneous route or the intranasal route, should be considered in the treatment of persistent severe cases refractory to conventional treatment. Despite all the available therapeutic agents, there continues to be a constant need to discover more effective ways to treat seasonal and perennial allergic conjunctivitis. This article also discusses recent patents related to the field.

Hydrocortisone concentration influences time to clinically significant healing of acute inflammation of the ocular surface and adnexa - results from a double-blind randomized controlled trial.

BackgroundThe efficacy of topical ophthalmic corticosteroids depends upon small modifications in preparations, such as drug concentration.The aim of this study was to confirm that hydrocortisone acetate (HC-ac) ophthalmic ointments of 2.5% and 1% are more effective than a 0.5% eye ointment.MethodsIn this randomized, double-blind, placebo-controlled, parallel-group clinical study, the change of signs and symptoms of acute inflammation of the ocular surface and adnexa was evaluated in 411 subjects.ResultsMedian time to clinically relevant response as estimated by 50% reduction in clinical signs and symptoms (CSS) total score over the entire trial was similar for subjects treated with HC-ac 2.5% (73.5 h) and for subjects treated with HC-ac 1.0% (67.7 h) and was considerably and significantly longer for subjects treated with HC-ac 0.5% (111.8 h) [p < 0.001 for both dosages]. All trial medications were safe and well tolerated.ConclusionHydrocortisone acetate 2.5% and Hydrocortisone acetate 1% eye ointments are efficacious and safe treatments for acute inflammations of the ocular surface or adnexa, and showed significantly better efficacy than a control group treated with Hydrocortisone acetate 0.5% therapy.Trial registrationCurrent Controlled Trials ISRCTN15464650.