Efficacy of adjunctive therapy using Vizoovet in improving clinical signs of keratoconjunctivitis sicca in dogs: A pilot study.

OBJECTIVE: To assess the clinical safety and efficacy of adjunctive therapy using Vizoovet to ameliorate clinical signs of keratoconjunctivitis sicca (KCS) in dogs. ANIMALS STUDIED: Twenty client-owned dogs. PROCEDURES: Canine patients diagnosed with KCS were enrolled in this prospective study. Patients were randomly selected to receive either Vizoovet or GenTeal drops twice daily in addition to twice daily tacrolimus 0.03% solution. Data were collected from only one eye of each patient and included STT-1, IOP, TFBUT, and results of objective clinical scoring performed by pet owners. Statistical significance was set at P ≤ .05. RESULTS: In all, 20 dogs (20 eyes) were enrolled in this prospective randomized study. Females (n = 12; 60%) outnumbered males (n = 8; 40%) and all dogs were spayed/neutered. Mean age of all dogs was 10.6 ± 3.79 years. In both treatment groups, the improvement in STT-1 values over the course of the study was significant (P = .002). When comparing the STT-1 improvements between groups, no significance was found (P = .78). In both groups, the improvement in TFBUT was significant (P = .0018). When comparing the TFBUT improvements between groups, no significance was found (P = .14). Squinting, rubbing, ocular discharge, and medication administration scores all significantly improved throughout the course of the study; however, they did not differ significantly between groups. Throughout the study, no adverse side effects were noted clinically or by the pet owner in either group. CONCLUSIONS AND CLINICAL RELEVANCE: Adjunctive treatment with Vizoovet was as safe and effective as GenTeal drops at improving clinical signs of dry eye in dogs.

Apricot Kernel Extract and Amygdalin Inhibit Urban Particulate Matter-Induced Keratoconjunctivitis Sicca.

Exposure to particulate matter is a risk factor for various ocular surface diseases, including keratoconjunctivitis sicca (KCS). In this study, we investigated the protective effects of apricot kernel extract (AKE) and its bioactive compound, amygdalin, on KCS induced by exposure to urban particulate matter (UPM). In the in vivo experiments, eye drops containing 0.5 mg/mL AKE (AKE-0.5) or 1 mg/mL AKE (AKE-1) were administered directly into the eyes of female rats after UPM exposure. Additionally, the effect of AKE and amygdalin on matrix metalloproteinases (MMPs) activity and the expressions of inflammatory factors, including tumor necrosis factor (TNF)-α and interleukin (IL)-6, was investigated in conjunctival epithelial cells in vitro. Topical administration of AKE-1 attenuated UPM exposure-induced reduction of tear secretion. Both AKE-0.5 and AKE-1 inhibited UPM exposure-induced corneal epithelial damage and irregularity. AKE also protected against UPM exposure-induced disruption of the mucin-4 layer on the ocular surface. In addition, AKE and amygdalin prevented UPM-induced activation of MMPs and upregulation of TNF-α and IL-6 in conjunctival epithelial cells. Therefore, AKE may have protective effects against UPM exposure-induced KCS via the inhibition of MMPs and inflammation. The pharmacological activities of AKE may be in part due to its bioactive compound, amygdalin.

Oral omega 3 in different proportions of EPA, DHA, and antioxidants as adjuvant in treatment of keratoconjunctivitis sicca in dogs / Ômega 3 oral em diferentes proporções de EPA, DHA e antioxidantes como adjuvante no tratamento de ceratoconjuntivite seca em cães

ABSTRACT Purpose: To compare the efficacy of 0.03% to­pical tacrolimus in combination with oral omega (ω) 3 with different ratios of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and antioxidants as adjuvant in the treatment of keratoconjunctivitis sicca (KCS) in dogs. Methods: Forty-five dogs with KCS were evaluated monthly for 6 months. Evaluations included performance of the Schirmer tear, fluorescein, and lissamine green tests. Tear film break-up time (TBUT) was assessed. Conjunctival cytology was evaluated at the beginning, middle, and end of the study. Conjunctiva was biopsied at the beginning and end of the study. Dogs were randomly assigned to one of the three groups (n=15): Group T (topical tacrolimus 0.03%), Group TO (topical tacrolimus + ω-1.5 EPA: 1 DHA), or Group TOA (topical tacrolimus + ω-1 EPA:4.5 DHA + antioxidants). Results: There was a significant improvement in clinical signs in all groups. TBUT increased throughout treatment in all groups; this effect was most pronounced in Group TO. Cytological analysis performed at the end of the study period, showed decreased levels of lymphocytes, neutrophils, and metaplastic and squamous cells in Groups T, TO, and TOA. Histological analysis performed at the end of the study period showed decreased levels of lymphocytes and neutrophils and increased levels of goblet cells. These effects were most pronounced in Group TO. Conclusion: Oral treatment with ω-3 containing a higher proportion of EPA than DHA increased the effectiveness of topical tacrolimus 0.03% in the treatment of keratoconjunctivitis sicca in dogs.

RESUMO Objetivo: Comparar a eficácia do tacrolimus 0,03% tópico associado ao ômega 3 oral, com diferentes proporções de ácido eicosapentaenoico (EPA), ácidos docosa-hexaenoicos (DHA) e antioxidantes, como adjuvante no tratamento de cães acometidos por ceratoconjuntivite seca. Métodos: Quarenta e cinco cães atendidos no Hospital Veterinário da UNOESTE portadores de ceratoconjuntivite seca foram avaliados mensalmente por 6 meses pelo Teste Lacrimal de Schirmer, Teste de Fluoresceína, Tempo de Ruptura do Filme Lacrimal, Teste de Rosa Bengala, citologia da conjuntiva no início, meio e fim do projeto e biopsia da conjuntiva no início e final do projeto. Os cães foram distribuídos aleatoriamente em 3 grupos (n=15): grupo T (tacrolimus 0,03% tópico), grupo TO (tacrolimus + ômegas 1.5 EPA/1 DHA oral) e grupo TOA (tacrolimus + ômegas 1 EPA/4,5 DHA + antioxidantes oral). Resultados: Houve uma melhora significativa nos sinais clínicos em ambos os grupos. No tempo de ruptura do filme lacrimal todos os grupos apresentaram aumento no decorrer do tratamento, sendo que o grupo TO foi o que apresentou melhor resultado em todos momentos quando comparado aos demais grupos. Ao final do experimento, os grupos T, TO e TOA apresentaram na análise citológica, diminuição de linfócitos, neutrófilos, células metaplásicas e escamosas, e na análise histopatológica, diminuição de linfócitos e neutrófilos e aumento das células caliciformes, com o grupo TO com melhor desempenho. Conclusão: O tratamento oral com ω-3 contendo uma maior proporção de EPA do que o DHA aumentou a eficácia do tacrolimus tópico 0,03% no tratamento de ceratoconjuntivite sicca em cães.

Oral omega 3 in different proportions of EPA, DHA, and antioxidants as adjuvant in treatment of keratoconjunctivitis sicca in dogs.

PURPOSE: To compare the efficacy of 0.03% to-pical tacrolimus in combination with oral omega (ω) 3 with different ratios of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and antioxidants as adjuvant in the treatment of keratoconjunctivitis sicca (KCS) in dogs. METHODS: Forty-five dogs with KCS were evaluated monthly for 6 months. Evaluations included performance of the Schirmer tear, fluorescein, and lissamine green tests. Tear film break-up time (TBUT) was assessed. Conjunctival cytology was evaluated at the beginning, middle, and end of the study. Conjunctiva was biopsied at the beginning and end of the study. Dogs were randomly assigned to one of the three groups (n=15): Group T (topical tacrolimus 0.03%), Group TO (topical tacrolimus + ω-1.5 EPA: 1 DHA), or Group TOA (topical tacrolimus + ω-1 EPA:4.5 DHA + antioxidants). RESULTS: There was a significant improvement in clinical signs in all groups. TBUT increased throughout treatment in all groups; this effect was most pronounced in Group TO. Cytological analysis performed at the end of the study period, showed decreased levels of lymphocytes, neutrophils, and metaplastic and squamous cells in Groups T, TO, and TOA. Histological analysis performed at the end of the study period showed decreased levels of lymphocytes and neutrophils and increased levels of goblet cells. These effects were most pronounced in Group TO. CONCLUSION: Oral treatment with ω-3 containing a higher proportion of EPA than DHA increased the effectiveness of topical tacrolimus 0.03% in the treatment of keratoconjunctivitis sicca in dogs.

Comparison of the efficacy of 0. 03% tacrolimus eye drops diluted in olive oil and linseed oil for the treatment of keratoconjunctivitis sicca in dogs / Comparação do colírio tacrolimus 0, 03% em óleo de oliva e linhaça no tratamento da ceratoconjuntivite seca em cães

ABSTRACT Objective: To compare the efficacy of 0.03% tacrolimus eye drops diluted in two different vehicles (linseed oil and olive oil) for the treatment of keratoconjunctivitis sicca (KCS) in dogs. Methods: This study included 60 dogs. Of this group, 20 were healthy and allocated to the control group, and 40 were diagnosed with bilateral KCS and randomly allocated to either the TO (tacrolimus in olive oil) or the TL (tacrolimus in linseed oil) groups. Ophthalmic examinations, Schirmer Tear Test-1 (STT-1), Tear Film Break-up Time (TBUT) and Fluorescein Test (FT) were carried out monthly, along with cytological and histopathological examinations at the beginning and end of the study. Results: The clinical signs, corneal ulcers, Schirmer Tear Test-1 values, and Tear Film Break-up Time values improved in both groups after one month of treatment. Cytological examination at the end of the study showed decreased lymphocytes, neutrophil, metaplastic, and squamous cell counts in both groups, while the histopathological analysis showed decreases in lymphocytes and neutrophils and an increase in goblet cell density (cells/mm2). The decreases in neutrophil count were more significant (p<0.05) in the TL group for both types of examination. Conclusion: In sum, 0.03% tacrolimus eye drops diluted in olive oil and linseed oil were effective in the treatment of keratoconjunctivitis sicca. None of the evaluated parameters differed significantly between the two groups, except for neutrophil count which was significantly lower in the TL group. Thus, linseed oil may be considered as an alternative diluent for tacrolimus eye drops.

RESUMO Objetivo: Comparar a eficácia do tacrolimus 0,03% colírio, diluído em óleo de linhaça e óleo de oliva, no tratamento de ceratoconjuntivite seca em cães. Métodos: Foram utilizados 60 cães; 20 cães saudáveis como grupo controle, e 40 cães com diagnóstico de ceratoconjuntivite seca bilateral, distribuídos aleatoriamente em dois grupos: Tacrolimus em óleo de oliva (TO) e Tacrolimus em óleo de semente de linhaça (TL). Os animais foram avaliados mensalmente com exames oftálmicos, Teste lacrimal de Schirmer-1 (TLS-1), Tempo de ruptura do filme lacrimal (TRFL) e Teste de Fluoresceína (TF), e mensalmente com citologia conjuntival e com exame histopatológico no início e final do estudo. Resultados: Nos dois grupos de tratamento os sinais clínicos, Teste lacrimal de Schirmer-1, óleo de semente de linhaça e Tempo de ruptura do filme lacrimal apresentaram melhora após um mês de tratamento. E no final do estudo, na análise citológica, ambos apresentaram diminuição de linfócitos, neutrófilos, células metaplásicas e células escamosas, e na análise histopatológica houve diminuição de linfócitos, neutrófilos e o aumento de células caliciformes. No grupo óleo de semente de linhaça, a diminuição de neutrófilos foi mais significativa (p<0,05) em ambas análises. Conclusão: Em suma, tacrolimus 0,03% colírio diluído em óleo de oliva e óleo de linhaça foram eficientes no tratamento de ceratoconjuntivite seca. Nenhum dos parâmetros avaliados diferiu significativamente entre os dois grupos, exceto a contagem de neutrófilos, que foi significativamente menor no grupo TL. Assim, o óleo de linhaça pode ser considerado como um diluente alternativo para o colírio tacrolimus.

Comparison of the efficacy of 0.03% tacrolimus eye drops diluted in olive oil and linseed oil for the treatment of keratoconjunctivitis sicca in dogs.

OBJECTIVE: To compare the efficacy of 0.03% tacrolimus eye drops diluted in two different vehicles (linseed oil and olive oil) for the treatment of keratoconjunctivitis sicca (KCS) in dogs. METHODS: This study included 60 dogs. Of this group, 20 were healthy and allocated to the control group, and 40 were diagnosed with bilateral KCS and randomly allocated to either the TO (tacrolimus in olive oil) or the TL (tacrolimus in linseed oil) groups. Ophthalmic examinations, Schirmer Tear Test-1 (STT-1), Tear Film Break-up Time (TBUT) and Fluorescein Test (FT) were carried out monthly, along with cytological and histopathological examinations at the beginning and end of the study. RESULTS: The clinical signs, corneal ulcers, Schirmer Tear Test-1 values, and Tear Film Break-up Time values improved in both groups after one month of treatment. Cytological examination at the end of the study showed decreased lymphocytes, neutrophil, metaplastic, and squamous cell counts in both groups, while the histopathological analysis showed decreases in lymphocytes and neutrophils and an increase in goblet cell density (cells/mm2). The decreases in neutrophil count were more significant (p<0.05) in the TL group for both types of examination. CONCLUSION: In sum, 0.03% tacrolimus eye drops diluted in olive oil and linseed oil were effective in the treatment of keratoconjunctivitis sicca. None of the evaluated parameters differed significantly between the two groups, except for neutrophil count which was significantly lower in the TL group. Thus, linseed oil may be considered as an alternative diluent for tacrolimus eye drops.

Clinical trials with multiple endpoints can establish a correlation, but not (yet) causality, between dietary supplementation with omega-3 fatty acids and keratoconjunctivitis sicca.

AIM: We review clinical evidence of therapeutic efficacy and effectiveness of omega-3 fatty acids (omega-3s) in keratoconjunctivitis sicca, colloquially known as dry eye disease. In doing so, we identify relevant literature to address the following questions: (1) What definitive guidance can clinical evidence offer eye physicians and their patients? (2) What aspects of omega-3 supplementation lack definitive evidence, and how might economic assessments help? METHODS: A targeted and systematic search strategy based on PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) was designed in this study for refereed clinical trials of omega-3s in dry eye treatment. Four key databases were accessed. Records were filtered through a three-step process using predetermined inclusion criteria. Data was extracted for experimental design, sample population characteristics, content of test and control groups, symptoms and associated opthalmologic conditions, diagnostic measures, patient health outcomes, adverse events, and model time horizon. RESULTS: A total of 219 records were initially identified, of which 21 prospective clinical trials, with a total of 2,973 participants, were admitted for review. Clinical evidence indicates that daily oral supplementation with omega-3s statistically correlates with dry eye treatment in the general symptomatic population as well as induced sub-populations. Reported adverse events are minimal. These trials nonetheless exhibit considerable heterogeneity in clinical endpoints, particularly as a result of the multi-factorial character of dry eye as well as continuous advances in scientific knowledge and technology. Their findings and recommendations appear to be of limited external validity. And causal inferences are needed, but difficult to establish. These have encouraged and sustained wide variations in ophthalmologic practice and normative decision-making. CONCLUSIONS: Comparability of omega-3 therapeutic efficacy and effectiveness remains a major challenge in dry eye disease management. Notwithstanding its multi-factorial character, addressing prevailing methodological and empirical issues in clinical trials will help reduce knowledge gaps and normative choices among eye physicians and patients alike. In this regard, pharmacoeconomics offers a useful and robust toolset through which analysis of cost-minimization, cost-effectiveness, and cost-utility as well as meta-analysis can be comparatively pursued. Blending measures of costs and outcomes puts in perspective the heterogeneity of clinical endpoints in keratoconjunctivitis sicca.

n-3 Fatty Acid Supplementation for the Treatment of Dry Eye Disease.

BACKGROUND: Dry eye disease is a common chronic condition that is characterized by ocular discomfort and visual disturbances that decrease quality of life. Many clinicians recommend the use of supplements of n-3 fatty acids (often called omega-3 fatty acids) to relieve symptoms. METHODS: In a multicenter, double-blind clinical trial, we randomly assigned patients with moderate-to-severe dry eye disease to receive a daily oral dose of 3000 mg of fish-derived n-3 eicosapentaenoic and docosahexaenoic acids (active supplement group) or an olive oil placebo (placebo group). The primary outcome was the mean change from baseline in the score on the Ocular Surface Disease Index (OSDI; scores range from 0 to 100, with higher scores indicating greater symptom severity), which was based on the mean of scores obtained at 6 and 12 months. Secondary outcomes included mean changes per eye in the conjunctival staining score (ranging from 0 to 6) and the corneal staining score (ranging from 0 to 15), with higher scores indicating more severe damage to the ocular surface, as well as mean changes in the tear break-up time (seconds between a blink and gaps in the tear film) and the result on Schirmer's test (length of wetting of paper strips placed on the lower eyelid), with lower values indicating more severe signs. RESULTS: A total of 349 patients were assigned to the active supplement group and 186 to the placebo group; the primary analysis included 329 and 170 patients, respectively. The mean change in the OSDI score was not significantly different between the active supplement group and the placebo group (-13.9 points and -12.5 points, respectively; mean difference in change after imputation of missing data, -1.9 points; 95% confidence interval [CI], -5.0 to 1.1; P=0.21). This result was consistent across prespecified subgroups. There were no significant differences between the active supplement group and the placebo group in mean changes from baseline in the conjunctival staining score (mean difference in change, 0.0 points; 95% CI, -0.2 to 0.1), corneal staining score (0.1 point; 95% CI, -0.2 to 0.4), tear break-up time (0.2 seconds; 95% CI, -0.1 to 0.5), and result on Schirmer's test (0.0 mm; 95% CI, -0.8 to 0.9). At 12 months, the rate of adherence to treatment in the active supplement group was 85.2%, according to the level of n-3 fatty acids in red cells. Rates of adverse events were similar in the two trial groups. CONCLUSIONS: Among patients with dry eye disease, those who were randomly assigned to receive supplements containing 3000 mg of n-3 fatty acids for 12 months did not have significantly better outcomes than those who were assigned to receive placebo. (Funded by the National Eye Institute, National Institutes of Health; DREAM ClinicalTrials.gov number, NCT02128763 .).

Noninvasive Electrical Stimulation for the Treatment of Chronic Ocular Pain and Photophobia.

INTRODUCTION: "Dry eye" or "keratoconjunctivitis sicca" is a multifactorial disease estimated to have a worldwide prevalence of 5-33%. Conventional therapies targeting the ocular surface with artificial tears, anti-inflammatories, punctal closure, eyelid hygiene, and antibiotics do not provide relief in all patients, especially those with neuropathic-like ocular complaints (wind hyperalgesia and photophobia). We anticipated that ocular transcutaneous electrical nerve stimulation (TENS) would alleviate symptoms of ocular pain, photophobia, and dryness in these latter individuals. METHODS: All individuals who received electrical stimulation between May 10, 2016 and April 6, 2017 for the treatment of chronic ocular pain at the oculofacial pain clinic of the Miami Veterans Administration Hospital were included in this retrospective review. All patients had symptoms of dryness along with other neuropathic-like symptoms (e.g., photophobia) and minimal signs of tear dysfunction. Ocular pain intensity, symptoms of dryness, and light sensitivity were compared pre-treatment and five min post-treatment via a two-tailed paired Student's t-test. RESULTS: The use of TENS significantly reduced the mean pain intensity in both the right and left eyes five min after treatment compared to prior to treatment (p < 0.05, paired t-test). The use of TENS significantly decreased light sensitivity in both eyes (p < 0.05). The findings for symptoms of dryness, however, were equivocal with a significant decrease in the left eye but not the right (p < 0.05, paired t-test). DISCUSSION: Our data indicate that TENS may similarly provide analgesia in patients with dry eye symptoms as it does for many other chronic pain conditions. Furthermore, the noted effect on symptoms of photophobia and dryness suggest that all may be linked by similar trigeminal-thalamic-cortical pathways. Prospective studies with electrical stimulation of dry eye are needed to further elucidate its benefit and mechanism of action.

TFOS DEWS II Management and Therapy Report.

The members of the Management and Therapy Subcommittee undertook an evidence-based review of current dry eye therapies and management options. Management options reviewed in detail included treatments for tear insufficiency and lid abnormalities, as well as anti-inflammatory medications, surgical approaches, dietary modifications, environmental considerations and complementary therapies. Following this extensive review it became clear that many of the treatments available for the management of dry eye disease lack the necessary Level 1 evidence to support their recommendation, often due to a lack of appropriate masking, randomization or controls and in some cases due to issues with selection bias or inadequate sample size. Reflecting on all available evidence, a staged management algorithm was derived that presents a step-wise approach to implementing the various management and therapeutic options according to disease severity. While this exercise indicated that differentiating between aqueous-deficient and evaporative dry eye disease was critical in selecting the most appropriate management strategy, it also highlighted challenges, based on the limited evidence currently available, in predicting relative benefits of specific management options, in managing the two dry eye disease subtypes. Further evidence is required to support the introduction, and continued use, of many of the treatment options currently available to manage dry eye disease, as well as to inform appropriate treatment starting points and understand treatment specificity in relation to dry eye disease subtype.

Clinical evaluation of a nutraceutical diet as an adjuvant to pharmacological treatment in dogs affected by Keratoconjunctivitis sicca.

BACKGROUND: Canine keratoconjunctivitis sicca (cKCS) is an inflammatory eye condition related to a deficiency in the tear aqueous fraction. Etiopathogenesis of such disease is substantially multifactorial, combining the individual genetic background with environmental factors that contribute to the process of immunological tolerance disruption and, as a consequence, to the emergence of autoimmunity disease. In this occurrence, it is of relevance the role of the physiological immune-dysregulation that results in immune-mediated processes at the basis of cKCS. Current therapies for this ocular disease rely on immunosuppressive treatments. Clinical response to treatment frequently varies from poor to good, depending on the clinical-pathological status of eyes at diagnosis and on individual response to therapy. In the light of the variability of clinical response to therapies, we evaluated the use of an anti-inflammatory/antioxidant nutraceutical diet with potential immune-modulating activity as a therapeutical adjuvant in cKCS pharmacological treatment. Such combination was administered to a cohort of dogs affected by cKCS in which the only immunosuppressive treatment resulted poorly responsive or ineffective in controlling the ocular symptoms. RESULTS: Fifty dogs of different breeds affected by immune-mediated cKCS were equally distributed and randomly assigned to receive either a standard diet (control, n = 25) or the nutraceutical diet (treatment group, n = 25) both combined with standard immunosuppressive therapy over a 60 days period. An overall significant improvement of all clinical parameters (tear production, conjunctival inflammation, corneal keratinization, corneal pigment density and mucus discharge) and the lack of food-related adverse reactions were observed in the treatment group (p < 0.0001). CONCLUSIONS: Our results showed that the association of traditional immune-suppressive therapy with the antioxidant/anti-inflammatory properties of the nutraceutical diet resulted in a significant amelioration of clinical signs and symptoms in cKCS. The beneficial effects, likely due to the presence of supplemented nutraceuticals in the diet, appeared to specifically reduce the immune-mediated ocular symptoms in those cKCS-affected dogs that were poorly responsive or unresponsive to classical immunosuppressive drugs. These data suggest that metabolic changes could affect the immune response orchestration in a model of immune-mediated ocular disease, as represented by cKCS.

Expert opinion in the management of aqueous Deficient Dry Eye Disease (DED).

BACKGROUND: Dry eye disease (DED) affects millions of people worldwide. There are a variety of new treatments beyond traditional therapies such as preservative free artificial tears. Here, we conduct a survey to identify the most common treatments used among specialists and assess their interest in newer therapies. METHODS: An international survey was distributed to dry eye researchers and expert practitioners via an internet survey. The survey data collected were analyzed with descriptive statistics. RESULTS: One hundred and fifteen respondents completed the survey; of these, 66 % were cornea specialists. The most commonly prescribed topical treatments included cyclosporine A (CSA) 0.05 % (71/104, 68 %), fluorometholone (FML) 0.1 % (59/99, 60 %), loteprednol etabonate 0.5 % (50/99, 51 %), and autologous serum eye drops (ASD; 48/97, 49 %). The most commonly prescribed non-topical medications included essential fatty acid supplements (72/104, 69 %), low-dose doxycycline (oral; 61/100, 61 %), and flaxseed supplements (32/96, 33 %) as well as punctal plugs (76/102, 75 %). Respondents reported treatment with topical corticosteroids for 2 to 8 weeks (46/86, 53 %), followed by less than 2 weeks (24/86, 28 %) and with topical CSA between 2 to 8 weeks (45/85, 53 %) followed by 2 to 6 months (24/85, 28 %). The top three signs and symptoms reported to indicate treatment response were, in order, fluorescein staining of the cornea, reduction in foreign body sensation, and reduction in burning sensation. CONCLUSION: This survey offers insight into current expert opinion in the treatment of DED. The results of this survey are hypothesis generating and will aid in the design of future clinical studies.

Comparison of 1% cyclosporine eye drops in olive oil and in linseed oil to treat experimentally-induced keratoconjunctivitis sicca in rabbits.

PURPOSE: To evaluate the effectiveness of topical 1% cyclosporine eye drops diluted in either of the two vehicles-olive and linseed oil-and that of the oils themselves in treating experimentally-induced keratoconjunctivitis sicca (KCS) in rabbits. METHODS: KCS was induced in 25 New Zealand rabbits using 1% atropine sulfate eye drops for 7 days before treatment and throughout the treatment period (12 weeks). The rabbits were divided into five groups: one control (C) group without KCS induction and four treatment groups in which KCS was induced and treated topically with olive oil (O), linseed oil (L), cyclosporine in olive oil (CO), and cyclosporine in linseed oil (CL). The animals were evaluated using Schirmer tear test 1 (STT), the fluorescein test (FT), tear-film break-up time (TBUT), the rose bengal test (RBT), and histopathological analysis. RESULTS: Values of STT and TBUT significantly decreased 1 week post-induction (p<0.05) and were similar to initial values after the 4th week of treatment, in all groups. After KCS induction, there was significantly less corneal damage in group L than in group CL, as assessed FT and RBT. Histopathology demonstrated that Groups L and CL presented less edema and corneal congestion. There was no significant difference in the goblet cell density (cells/mm2) between the groups (p=0.147). CONCLUSION: Cyclosporine diluted in olive oil or linseed oil was effective in the treatment of KCS, although it had better efficacy when diluted in linseed oil. Linseed oil presented better effectiveness, whether associated or not, than olive oil. These results may contribute to the creation of novel topical ophthalmic formulations for KCS treatment in future.

Comparison of 1% cyclosporine eye drops in olive oil and in linseed oil to treat experimentally-induced keratoconjunctivitis sicca in rabbits / Comparação da ciclosporina 1% em óleo de oliva e óleo de linhaça no tratamento da ceratoconjuntivite seca experimentalmente induzida em coelhos

ABSTRACTPurpose:To evaluate the effectiveness of topical 1% cyclosporine eye drops diluted in either of the two vehicles-olive and linseed oil-and that of the oils themselves in treating experimentally-induced keratoconjunctivitis sicca (KCS) in rabbits.Methods:KCS was induced in 25 New Zealand rabbits using 1% atropine sulfate eye drops for 7 days before treatment and throughout the treatment period (12 weeks). The rabbits were divided into five groups: one control (C) group without KCS induction and four treatment groups in which KCS was induced and treated topically with olive oil (O), linseed oil (L), cyclosporine in olive oil (CO), and cyclosporine in linseed oil (CL). The animals were evaluated using Schirmer tear test 1 (STT), the fluorescein test (FT), tear-film break-up time (TBUT), the rose bengal test (RBT), and histopathological analysis.Results:Values of STT and TBUT significantly decreased 1 week post-induction (p<0.05) and were similar to initial values after the 4th week of treatment, in all groups. After KCS induction, there was significantly less corneal damage in group L than in group CL, as assessed FT and RBT. Histopathology demonstrated that Groups L and CL presented less edema and corneal congestion. There was no significant difference in the goblet cell density (cells/mm2) between the groups (p=0.147).Conclusion:Cyclosporine diluted in olive oil or linseed oil was effective in the treatment of KCS, although it had better efficacy when diluted in linseed oil. Linseed oil presented better effectiveness, whether associated or not, than olive oil. These results may contribute to the creation of novel topical ophthalmic formulations for KCS treatment in future.

RESUMOObjetivo:Avaliar a eficácia do uso tópico do colírio de ciclosporina 1% em dois veículos, óleo de oliva e linhaça, e dos óleos separados, no tratamento da ceratoconjuntivite seca experimentalmente induzida (KCS) em coelhos.Método:Vinte e cinco coelhos Nova Zelândia foram induzidos para KCS com colírio de sulfato de atropina a 1% por sete dias antes e durante o período de tratamento (12 semanas) e foram divididos em 5 grupos, um grupo controle (C), sem indução de KCS e quatro grupos de tratamento tópico com ciclosporina em óleo de oliva (CO), ciclosporina em óleo de linhaça (CL), óleo de oliva (O) e óleo de linhaça (L). Os animais foram avaliados utilizando o teste lacrimal de Schirmer I (STT), teste de fluoresceína (FT), teste de ruptura do filme lacrimal (TBUT), teste de rosa bengala (RBT) e análise histopatológica.Resultados:Os valores de TBUT e STT diminuíram significativamente uma semana pós-indução da KCS (p<0,05) e foram semelhantes aos valores iniciais após a quarta semana de tratamento, em todos os grupos. Após a indução de KCS, houve menor dano na córnea no grupo L em relação ao grupo CL, quando avaliados FT e RBT. A histopatologia demonstrou que os grupos L e CL apresentaram menos edema e congestão da córnea. Não houve diferença significativa na densidade das células caliciformes (células/mm2) entre os grupos (p=0,147).Conclusão:Ciclosporina diluída em óleo de oliva ou linhaça foi eficiente no tratamento da CCS, porém teve uma melhor eficácia quando diluída no óleo de linhaça. O óleo de linhaça, isoladamente ou associado, apresentou melhor eficácia quando comparado ao óleo de oliva. Estes resultados podem contribuir no futuro com novas formulações oftálmicas tópicas no tratamento da CCS.

Efficacy and safety of topical diquafosol ophthalmic solution for treatment of dry eye: a systematic review of randomized clinical trials.

PURPOSE: To evaluate the efficacy and safety of topical diquafosol ophthalmic solution for treatment of dry eye. METHODS: Randomized clinical trials (RCTs) from MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) were identified to evaluate the efficacy and safety of topical administration of diquafosol to patients with dry eyes. Data evaluation was based on endpoints including Schirmer test, tear film break-up time, ocular surface staining score, subjective symptom score, and adverse events. RESULTS: A total of 8 RCTs involving 1516 patients were selected based on the prespecified criteria. Significant improvement of Schirmer test values and tear film break-up time were reported in 40% (2 of 5) and 80% (4 of 5) studies, respectively. Ocular surface staining scores significantly decreased in 100% (fluorescein corneal staining, 6 of 6; Rose Bengal corneal and conjunctival staining, 4 of 4) RCTs. Symptoms significantly improved in 75% (6 of 8) RCTs in patients with dry eyes. No severe adverse events were reported with the concentration of diquafosol from 0.5% to 5%. Heterogeneity in study design prevented meta-analysis from statistical integration and summarization. CONCLUSIONS: Topical diquafosol seems to be a safe therapeutic option for the treatment of dry eye. The high variability of the selected RCTs compromised the strength of evidence and limits the determination of efficacy. However, the topical administration of diquafosol seems to be beneficial in improving the integrity of the epithelial cell layer of the ocular surface and mucin secretion in patients with dry eyes. This review indicates a need for standardized criteria and methods for evaluation to assess the efficacy of diquafosol in the future clinical trials.

Comparação entre dois protocolos de tratamento de ceratoconjuntivite seca experimentalmente induzida em coelhos / Comparison of two treatment protocols of experimentally induced keratoconjunctivitis sicca in rabbits

O objetivo deste estudo foi avaliar e comparar a eficácia de dois protocolos de tratamento de ceratoconjuntivite seca (CCS) experimentalmente induzida em coelhos: uma formulação oftálmica tópica composta por álcool polivinílico 1,4%, adicionado com acetilcisteína 10% e pilocarpina 1% (AAP), e outro protocolo com o uso do óleo de semente de linhaça (OL) tópico em forma de colírio, durante 12 semanas. Foram utilizados 15 coelhos machos, adultos, da raça Nova Zelândia, alocados aleatoriamente em três grupos: grupo C (controle), grupo AAP (formulação oftálmica) e grupo L (OL tópica). Os animais foram avaliados semanalmente pelo teste lacrimal de Schirmer, teste de fluoresceína e teste de Rosa Bengala; uma vez por mês, pelo exame de citologia esfoliativa ocular; ao final do experimento, pela análise histopatológica da córnea e conjuntiva. Os resultados demonstraram que houve um aumento maior na produção lacrimal quando utilizada a formulação oftálmica, e uma resolução mais rápida das úlceras de córnea, bem como diminuição no número de células desvitalizadas quando utilizado o óleo de semente de linhaça, além de aumento no número de células caliciformes em ambos os grupos de tratamento. A associação desses dois protocolos pode ser no futuro uma alternativa no tratamento da CCS.

The objective of this study was to evaluate and compare the effectiveness of two treatment protocol of experimentally induced keratoconjunctivitis sicca (KCS) in rabbits, a topical ophthalmic formulation composed by 1.4% povinilic alcohol added with 10% acetylcysteine and 1% pilocarpine (AAP) and another protocol with the topical use of the linseed seed oil (LO) in eye drop form f or 12 weeks. Fifteen male New Zealand white rabbits were aleatory allocated in 3 groups: Group C (Control), Group AAP (ophthalmic formulation) and Group L (LO topical). The animals were evaluated weekly using the Schirmer's tear test, fluorescein test and Rose Bengal test monthly for ocular cytology, and at the end of the experiment for histopathological analysis of cornea and conjunctive. The results demonstrated that there was a larger increase in the tear production when the ophthalmic formulation was us ed and a faster rapid resolution of corneal ulcers and decrease in the number of devitalized cells when linseed seed oil was used, besides an increase in the number of caliciform cells in both treatment groups. The association of those two protocols can be a future alternative in the treatment of KCS.

Long-term Supplementation With n-6 and n-3 PUFAs Improves Moderate-to-Severe Keratoconjunctivitis Sicca: A Randomized Double-Blind Clinical Trial.

PURPOSE: Supplementation with gamma-linolenic acid (GLA) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) has been found to decrease the production of disease-relevant inflammatory mediators that are implicated in the pathogenesis of chronic dry eye. This study evaluated the effect of a supplement containing both GLA and n-3 PUFAs on signs and symptoms of moderate-to-severe keratoconjunctivitis sicca in postmenopausal patients. METHODS: This multicenter, double-masked placebo-controlled clinical trial enrolled 38 patients (both eyes) with tear dysfunction who were randomized to supplemental GLA + n-3 PUFAs or placebo for 6 months. Disease parameters, including Ocular Surface Disease Index, Schirmer test, tear breakup time, conjunctival fluorescein and lissamine green staining, and topographic corneal smoothness indexes (surface asymmetry index and surface regularity index), were assessed at baseline and at 4, 12, and 24 weeks. The intensity of dendritic cell CD11c integrin and HLA-DR expression was measured in conjunctival impression cytologies. RESULTS: The Ocular Surface Disease Index score improved with supplementation and was significantly lower than placebo (21 ± 4 vs. 34 ± 5) after 24 weeks (P = 0.05, n = 19 per group). The surface asymmetry index was significantly lower in supplement-treated subjects (0.37 ± 0.03, n = 15) than placebo (0.51 ± 0.03, n = 16) at 24 weeks (P = 0.005). Placebo treatment also significantly increased HLA-DR intensity by 36% ± 9% and CD11c by 34% ± 7% when compared with supplement treatment (n = 19 per group, P = 0.001, 24 weeks). Neither treatment had any effect on tear production, tear breakup time, or corneal or conjunctival staining. CONCLUSIONS: Supplemental GLA and n-3 PUFAs for 6 months improved ocular irritation symptoms, maintained corneal surface smoothness, and inhibited conjunctival dendritic cell maturation in patients with postmenopausal keratoconjunctivitis sicca.Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00883649.

Corneal ulceration in a LASIK patient due to vitamin a deficiency after bariatric surgery.

PURPOSE: To review the case of a 41-year-old woman who underwent bariatric surgery in 2000. She subsequently underwent laser in situ keratomileusis (LASIK) surgery in 2008 and complained of dry eye since the LASIK surgery. In November 2010, she was diagnosed with a corneal melt and was treated with aggressive lubrication, followed by eventual amniotic membrane placement and a tarsorrhaphy. She then presented for consultation at the Bascom Palmer Eye Institute when she developed a corneal infiltrate. She was diagnosed with fungal keratitis with corneal xerosis. At that time, vitamin A levels were measured and were less than 2 µ/dL. The patient admitted noncompliance with nutritional supplements. METHODS: Case report. RESULTS: The patient was treated with aggressive lubrication and natamycin. Vitamin supplements were restarted, and the patient experienced dramatic improvement in symptoms with resolution of the infection. A central corneal scar with corneal thinning remains. The patient underwent a penetrating keratoplasty for visual rehabilitation. CONCLUSIONS: Patient education with emphasis on compliance with nutritional supplements is essential after bariatric surgery. Consider vitamin A deficiency in the differential diagnosis of dry eye after LASIK surgery.

Treatment of severe keratoconjunctivitis sicca by parotid duct transposition after tympanic neurectomy in rabbits.

PURPOSE: To investigate the feasibility of parotid duct transposition after tympanic neurectomy to treat severe keratoconjunctivitis sicca (KCS) in rabbits. METHODS: Thirty rabbits were divided into three groups in experiment 1. One eye was operated on, and the contralateral eye served as the control. In the KCS group, the lacrimal gland, harderian gland, and nictitating membrane were removed. In the group with parotid duct transposition (DT), the parotid duct was transposed into the lower conjunctival fornix. In the group with parotid duct transposition after tympanic neurectomy (DTTN), the tympanic nerve was resected in addition to parotid duct transposition. Schirmer test was performed and density of corneal staining was determined monthly after surgery, and goblet cell density was measured at postoperative month 3. In experiment 2, the tympanic nerve was resected on one side in 12 rabbits. Both sides of the parotid gland were resected for histopathology at intervals of 2 months to 1 year after surgery. RESULTS: Tear secretion from operated eyes at rest increased significantly after surgery in the treatment groups compared with the KCS group. Tear secretion from operated eyes after chewing was significantly lower in the DTTN than in the DT group. The corneal staining scores were higher in the operated than in the control eyes of the three groups, without significant difference among the operated eyes. Parotid gland atrophy on the operated side occurred at postoperative month 4 and recovered to normal 1 year after surgery. CONCLUSIONS: Parotid duct transposition after tympanic neurectomy could effectively reduce gustatory epiphora but may be insufficient to promote ocular surface health.

Changes in the evaporation rate of tear film after digital expression of meibomian glands in patients with and without dry eye.

PURPOSE: To evaluate the effect of excess meibum on tear evaporation rate in patients with and without dry eye. METHODS: Eleven healthy subjects and 16 patients with dry eye were tested. The dry eye group was divided into 2 subgroups: classic keratoconjunctivitis sicca (KCS) with clear and easily expressed meibum and KCS with meibomian gland dysfunction (MGD) with turbid secretions and difficult-to-express meibum. Evaporative measurements were performed at baseline and after digital expression of meibomian glands at 12, 24, 36, and 48 minutes. Two ranges of relative humidity were used, 25% to 35% and 35% to 45%. The data were expressed as microliters per square centimeter per minute. RESULTS: An increase in the evaporation rate of the tear film was noted for all measurements at both relative humidities in the classic KCS and KCS with MGD groups compared with healthy subjects (P < 0.05). The average evaporation rates at relative humidities of 25% to 35% and 35% to 45% were 0.056 ± 0.016 and 0.040 ± 0.008 for the classic KCS group; 0.055 ± 0.026 and 0.037 ± 0.019 for the KCS with MGD group and 0.033 ± 0.012 and 0.023 ± 0.008 for the healthy group. Also, a decrease in the evaporation rate was observed in the healthy and KCS with MGD groups between baseline and the first measurement after digital expression for both relative humidities (P < 0.05). The classic KCS group did not show any changes after expression. CONCLUSIONS: Classic KCS and KCS with MGD groups showed an increase in tear evaporation rates compared with the healthy group. Aqueous tear evaporation diminished in the healthy and KCS with MGD groups after expression of meibomian glands. However, this effect was transient and negligible after the second measurement.