Association between systemic activity index and dry eye severity in patients with primary Sjögren syndrome / A associação entre o índice de atividade sistêmica e a severidade do olho seco em pacientes com síndrome de Sjögren primária

ABSTRACT Purpose: The aim of the present study was to compare the severity of ocular and systemic findings among patients with primary Sjögren syndrome. Methods: The study followed a prospective controlled design and comprised two groups; the test group included 58 eyes of 58 patients newly diagnosed with primary Sjögren syndrome with poor dry eye test findings and the control group included 45 right eyes of 45 healthy age- and sex-matched individuals. The ocular surface disease index score, tear osmolarity, Schirmer I test without anesthesia, fluorescein tear breakup time, and cornea-conjunctiva staining with lissamine green (van Bijsterveld scoring) were used to examine tear function in the patients via a complete ophthalmological examination. The results were graded and classified on the basis of a Dry Eye WorkShop report and results of the corneal and conjunctival staining test, Schirmer's test, and fluorescein tear breakup time test. Discomfort, severity and frequency of symptoms, visual symptoms, conjunctival injection, eyelid-meibomian gland findings, and corneal-tear signs were interpreted. Disease activity was scored per the EULAR Sjögren's syndrome disease activity index (ESSDAI) via systemic examination and laboratory evaluations, and the EULAR Sjögren's syndrome patient-reported index (ESSPRI) assessed via a survey of patient responses. Results: Mean patient age was 48.15 ± 16.34 years in the primary Sjögren syndrome group and 44.06 ± 9.15 years in the control group. Mean fluorescein tear breakup time was 4.51 ± 2.89s in the primary Sjögren syndrome group and 10.20 ± 2.39 s in the control group. Mean Schirmer I test result was 3.51 ± 3.18 mm/5 min in the primary Sjögren syndrome group and 9.77±2.30 mm/5 min in the control group. Mean ocular surface disease index score was 18.56 ± 16.09 in the primary Sjögren syndrome group, and 19.92 ± 7.16 in the control group. Mean osmolarity was 306.48 ± 19.35 in the primary Sjögren syndrome group, and 292.54 ± 10.67 in the control group. Mean lissamine green staining score was 2.17 ± 2.76 in the primary Sjögren syndrome group, and 0.00 in the control group. Statistically significant differences were found berween the primary Sjögren syndrome group and control group in terms of fluorescein tear breakup time, Schirmer's test, lissamine green staining, and osmolarity tests (p=0.036, p=0.041, p=0.001, and p=0.001 respectively). The Dry Eye WorkShop score was 2.15 ± 0.98, the EULAR Sjögren's syndrome disease activity index score was 11.18 ± 4.05, and the EULAR Sjögren's syndrome patient-reported index score was 5.20±2.63. When potential associations of the Dry Eye Workshop Study scores and osmolarity scores with the Eular Sjögren's syndrome disease activity index scores were evaluated, the results were found to be statistically significant (p=0.001, p=0.001 respectively). Conclusion: The results showed an association between dry eye severity and systemic activity index in primary Sjögren syndrome patients.

RESUMO Objetivo: O objetivo do presente estudo foi comparar a gravidade dos achados oculares e sistêmicos entre pacientes com síndrome de Sjögren primária. Métodos: O estudo seguiu um delineamento prospectivo controlado e compreendeu dois grupos; o grupo de teste incluiu 58 olhos de 58 pacientes recém-diagnosticados com síndrome de Sjögren primária com resultados deficientes no teste de olho seco e o grupo controle incluiu 45 olhos direitos de 45 indivíduos saudáveis pareados idade e sexo. A contagem do índice de doença da superfície ocular, osmolaridade lacrimal, teste de Schirmer I sem anestesia, tempo de ruptura da fluoresceína e coloração córnea-conjuntiva com verde de lissamina (índice de van Bijsterveld) foram utilizados para examinar a função lacrimal dos pacientes através de exame oftalmológico completo. Os resultados foram classificados com base em um relatório da "Dry Eye Workshop" e resultados do teste de coloração da córnea e conjuntiva, teste de Schirmer e teste do tempo de ruptura da fluoresceína. Desconforto, gravidade e frequência dos sintomas, sintomas visuais, injeção conjuntival, achados das glândulas palpebrais e sinais da córnea foram interpretados. A atividade da doença foi avaliada pelo índice de atividade da doença da síndrome de Sjögren EULAR por meio de exame sistêmico e avaliações laboratoriais, e o índice relatado pelo paciente da síndrome de Sjörgen EULAR avaliado através de uma pesquisa das respostas dos pacientes. Resultados: A média de idade dos pacientes foi de 48,15 ± 16,34 anos no grupo da Síndrome de Sjörgen primária e 44,06 ± 9,15 anos no grupo controle. O tempo médio de ruptura da fluoresceína foi de 4,51 ± 2,89 s no grupo síndrome de Sjögren primária e 10,20 ± 2,39 s no grupo controle. O resultado do teste de Schirmer I médio foi de 3,51 ± 3,18 mm/5 min no grupo síndrome de Sjögren primária e de 9,77 ± 2,30 mm/5 min no grupo controle. O índice médio de doença da superfície ocular foi de 18,56 ± 16,09 no grupo síndrome de Sjögren primária e 19,92 ± 7,16 no grupo controle. A osmolaridade média foi 306,48 ± 19,35 no grupo síndrome de Sjögren primária e 292,54 ± 10,67 no grupo controle. O resultado médio de coloração com lissamina verde foi de 2,17 ± 2,76 no grupo síndrome de Sjögren primária e 0,00 no grupo controle. Diferenças es­tatisticamente significativas foram encontradas entre o com sín­­drome de Sjögren primária e o grupo controle em termos de tempo de ruptura da fluoresceína lacrimal, teste de Schirmer I, coloração com lissamina verde e osmolaridade (p=0,036, p=0,041, p=0,001, p=0,001 respectivamente). O índice Estudo do Olho Seco foi de 2,15 ± 0,98, o índice de atividade da doença da síndrome de Sjögren EULAR foi de 11,18 ± 4,05 e a pontuação do índice relatado pelo paciente EULAR Sjögren foi de 5,20 ± 2,63. Quando associações potenciais do Estudo do Olho Seco e o índice da osmolaridade foram comparados a pontuação de índice de atividade da doença da síndrome de Sjögren EULAR, os resultados foram estatisticamente significantes (p=0,001, p=0,001 respectivamente). Conclusão: Os resultados mostraram uma associação entre a gravidade do olho seco e o índice de atividade sistêmica em pacientes com síndrome de Sjögren primária.

Nuclear parameters and chromatin remodeling in epithelial cells and lymphocytes from the palpebral conjunctiva of dogs with keratoconjunctivitis sicca.

OBJECTIVE: To study parameters related to nuclear morphology and chromatin remodeling in epithelial cells and lymphocytes from the inferior palpebral conjunctiva of dogs with and without keratoconjunctivitis sicca (KCS). ANIMALS STUDIED: Thirty-two dogs (64 eyes) were included in the study. Based on the tear production measured by Schirmer tear test 1, the dogs were distributed into control and KCS groups. PROCEDURES: Epithelial cells and lymphocytes were collected by conjunctival brush cytology, fixed on glass slides, and subjected to the Feulgen reaction, a topochemical method specific for DNA/chromatin. Feulgen-stained cells were studied by microscopy and video image analysis to establish nuclear size (area and perimeter) and shape (relative nuclear roundness factor = RNRF), DNA content (ploidy), and compaction and texture of chromatin. RESULTS: Conjunctival samples in the KCS group showed infiltration of inflammatory and immune cells. Micronuclei, snake-like chromatin, aberrant chromosomes, and goblet cells were not detected. Compared with the controls, cells on the conjunctival surface of dogs with KCS showed altered nuclei. Conjunctival epithelial cells were more affected by KCS (changes in nuclear size, shape, DNA content, and chromatin compaction) than lymphocytes (changes in chromatin compaction, only). Significant chromatin decompaction was observed in both conjunctival epithelial cells and lymphocytes. CONCLUSIONS: Our results show that KCS promotes chromatin remodeling in epithelial cells and lymphocytes on the conjunctival surface of dogs. The changes described in this study are different from those reported for conjunctival cell nuclei of human KCS patients.

Association between systemic activity index and dry eye severity in patients with primary Sjögren syndrome.

PURPOSE: The aim of the present study was to compare the severity of ocular and systemic findings among patients with primary Sjögren syndrome. METHODS: The study followed a prospective controlled design and comprised two groups; the test group included 58 eyes of 58 patients newly diagnosed with primary Sjögren syndrome with poor dry eye test findings and the control group included 45 right eyes of 45 healthy age- and sex-matched individuals. The ocular surface disease index score, tear osmolarity, Schirmer I test without anesthesia, fluorescein tear breakup time, and cornea-conjunctiva staining with lissamine green (van Bijsterveld scoring) were used to examine tear function in the patients via a complete ophthalmological examination. The results were graded and classified on the basis of a Dry Eye WorkShop report and results of the corneal and conjunctival staining test, Schirmer's test, and fluorescein tear breakup time test. Discomfort, severity and frequency of symptoms, visual symptoms, conjunctival injection, eyelid-meibomian gland findings, and corneal-tear signs were interpreted. Disease activity was scored per the EULAR Sjögren's syndrome disease activity index (ESSDAI) via systemic examination and laboratory evaluations, and the EULAR Sjögren's syndrome patient-reported index (ESSPRI) assessed via a survey of patient responses. RESULTS: Mean patient age was 48.15 ± 16.34 years in the primary Sjögren syndrome group and 44.06 ± 9.15 years in the control group. Mean fluorescein tear breakup time was 4.51 ± 2.89s in the primary Sjögren syndrome group and 10.20 ± 2.39 s in the control group. Mean Schirmer I test result was 3.51 ± 3.18 mm/5 min in the primary Sjögren syndrome group and 9.77±2.30 mm/5 min in the control group. Mean ocular surface disease index score was 18.56 ± 16.09 in the primary Sjögren syndrome group, and 19.92 ± 7.16 in the control group. Mean osmolarity was 306.48 ± 19.35 in the primary Sjögren syndrome group, and 292.54 ± 10.67 in the control group. Mean lissamine green staining score was 2.17 ± 2.76 in the primary Sjögren syndrome group, and 0.00 in the control group. Statistically significant differences were found berween the primary Sjögren syndrome group and control group in terms of fluorescein tear breakup time, Schirmer's test, lissamine green staining, and osmolarity tests (p=0.036, p=0.041, p=0.001, and p=0.001 respectively). The Dry Eye WorkShop score was 2.15 ± 0.98, the EULAR Sjögren's syndrome disease activity index score was 11.18 ± 4.05, and the EULAR Sjögren's syndrome patient-reported index score was 5.20±2.63. When potential associations of the Dry Eye Workshop Study scores and osmolarity scores with the Eular Sjögren's syndrome disease activity index scores were evaluated, the results were found to be statistically significant (p=0.001, p=0.001 respectively). CONCLUSION: The results showed an association between dry eye severity and systemic activity index in primary Sjögren syndrome patients.

Effects of Muller's muscle-conjunctival resection for ptosis on ocular surface scores and dry eye symptoms.

This article evaluates the effects of Muller's muscle-conjunctival resection (MMCR) on ocular surface scores and dry eye symptoms. Forty-six patients were enrolled in the study. Eighteen underwent bilateral upper eyelid skin excision with MMCR and 28 underwent bilateral upper eyelid skin-only excision (control group). The Salisbury Eye Evaluation Questionnaire and an ocular surface evaluation protocol consisting of Schirmer's test, tear break-up time (TBUT), fluorescein and rose bengal corneal staining were performed during the pre-operative consultation and on postoperative days 7, 30, and 90. Improvement in symptoms questionnaire scores from baseline was observed on postoperative day 90 in the blepharoplasty plus MMCR group. There was no change in questionnaire scores in patients who underwent blepharoplasty alone. No between-group difference in Schirmer's test, TBUT, or fluorescein and rose bengal staining was found at any time point. In the blepharoplasty-only (control group), the fluorescein staining score was reduced on postoperative day 30 as compared to baseline, but not on day 90. In this sample, addition of MMCR to upper eyelid blepharoplasty did not worsen ocular surface scores or dry eye symptoms.

Bilirubin Concentrations in Jaundiced Neonates with Conjunctival Icterus.

OBJECTIVES: To assess the total serum bilirubin (TSB) levels at which conjunctival icterus is observed in neonates of ≥34 weeks gestation during the first week of life. STUDY DESIGN: Two convenience samples of neonates were examined for conjunctival icterus within 4 hours of TSB measurements. A concurrent assessment of cephalopedal cutaneous icterus was performed and the TSB characterized using the Bhutani hour-specific risk zone nomogram. RESULTS: Two hundred forty neonates were studied of which 76 had conjunctival icterus. Conjunctival icterus was always accompanied by cutaneous jaundice to at least the chest and more often than not a TSB >14.9 mg/dL (255 umol/L) consistently in the 76th%-95th% to >95th% range on the Bhutani nomogram. Only a few infants with TSB in the range of 10-14.9 mg/dL (171-255 umol/L) had conjunctival icterus. CONCLUSIONS: Conjunctival icterus was observed in a subset of jaundiced neonates and associated with elevated hour-specific TSB levels frequently >95th% on the Bhutani nomogram. Conjunctival icterus is a sign of clinically relevant hyperbilirubinemia that merits a TSB measurement and evaluation of the infant.

Accuracy of clinical pallor in the diagnosis of anaemia in children: a meta-analysis.

BACKGROUND: Anaemia is highly prevalent in children of developing countries. It is associated with impaired physical growth and mental development. Palmar pallor is recommended at primary level for diagnosing it, on the basis of few studies. The objective of the study was to systematically assess the accuracy of clinical signs in the diagnosis of anaemia in children. METHODS: A systematic review on the accuracy of clinical signs of anaemia in children. We performed an Internet search in various databases and an additional reference tracking. Studies had to be on performance of clinical signs in the diagnosis of anaemia, using haemoglobin as the gold standard. We calculated pooled diagnostic likelihood ratios (LR's) and odds ratios (DOR's) for each clinical sign at different haemoglobin thresholds. RESULTS: Eleven articles met the inclusion criteria. Most studies were performed in Africa, in children underfive. Chi-square test for proportions and Cochran Q for DOR's and for LR's showed heterogeneity. Type of observer and haemoglobin technique influenced the results. Pooling was done using the random effects model. Pooled DOR at haemoglobin <11 g/dL was 4.3 (95% CI 2.6-7.2) for palmar pallor, 3.7 (2.3-5.9) for conjunctival pallor, and 3.4 (1.8-6.3) for nailbed pallor. DOR's and LR's were slightly better for nailbed pallor at all other haemoglobin thresholds. The accuracy did not vary substantially after excluding outliers. CONCLUSION: This meta-analysis did not document a highly accurate clinical sign of anaemia. In view of poor performance of clinical signs, universal iron supplementation may be an adequate control strategy in high prevalence areas. Further well-designed studies are needed in settings other than Africa. They should assess inter-observer variation, performance of combined clinical signs, phenotypic differences, and different degrees of anaemia.

Increased expression of advanced glycation end-products and their receptor, and activation of nuclear factor kappa-B in lacrimal glands of diabetic rats.

AIMS/HYPOTHESIS: To assess the involvement of the AGE-specific receptor (AGER, also known as RAGE) axis and nuclear factor kappa-B (NFKB, also known as NF-kappaB) activation in the development of lacrimal gland and tear film dysfunction in diabetes, the present study evaluated: (1) lacrimal gland and tear film alterations in diabetic rats; and (2) the expression of AGE, AGER and NFKB in ocular tissues of normoglycaemic and diabetic rats. MATERIALS AND METHODS: Diabetes was induced in male Wistar rats with intravenous streptozotocin. Tear secretion parameters were measured and NFKB expression was evaluated in lacrimal glands of control and diabetic rats by western blot. Immunohistochemistry with confocal microscopy was used to assess AGE, AGER and NFKB expression in lacrimal glands of both groups. RESULTS: Lacrimal gland weight and tear film volume were lower in diabetic than in control rats (p=0.01 and 0.02, respectively). IL1B and TNF concentrations in tears were higher in diabetic than in control rats (p=0.007 and 0.02, respectively). NFKB protein was identified in rat cornea, conjunctiva and lacrimal glands. AGE, AGER and NFKB expression were greater in lacrimal glands of diabetic than in those of control rats. CONCLUSIONS/INTERPRETATION: Diabetes induces significant alterations in rat lacrimal gland structure and secretion. The higher expression of AGE, AGER and NFKB in lacrimal glands of diabetic rats suggests that these factors are involved in signalling and in subsequent inflammatory alterations related to dry eye in diabetes mellitus.

El ojo y la hipertensión arterial / The eye and high-blood pressure

En el presenta trabajo se describen las alteraciones que ocurren en algunas estructuras del órgano de la visión como consecuencia de la hipertensión arterial. No se detalla la correspondencia entre la alteración y tipo de hipertensión. Sólo se expone la descripción de cambios que ocurren en el paciente hipertenso. Las alteraciones de la retina y sus vasos vistas por oftalmoscopia ocupan el centro de esta revisión donde también se aportan algunas experiencias en el campo de la electrofisiología, así como las modificaciones encontradas en la microcirculación de la conjuntiva. Los cambios ocurridos en la retina se separan en 2 grupos y se señala la importancia de estos hallazgos en relación con el diagnóstico precoz, pronóstico y evolución de la hipertensión. Se describen las alteraciones electrofisiológicas en los capilares así como otros cambios menos frecuentes (la reducción del campo visual, la asociación glaucoma: hipertensión arterial y la disminución del sentido cromático)

[S.U.N.C.T. syndrome: report of a case preceded by ocular trauma]. / Síndrome de S.U.N.C.T. Relato de um caso precedido de trauma ocular.

Report case of Short lasting, Unilateral, Neuralgiform headache, associated to Conjunctival injection and Tearing (S.U.N.C.T. syndrome) preceded by ipsilateral ocular trauma. We are not aware of any other report of such association. Until the pathophysiology of the S.U.N.C.T. syndrome becomes completely clarified, the relationship between the preceding ocular trauma and the occurrence of the clinical manifestations remains speculative. Clinical, pathophysiological therapeutic aspects of the S.U.N.C.T. syndrome are reviewed.

Síndrome de S.U.N.C.T.: relato de um caso precedido de trauma ocular / S.U.N.C.T. syndrome: report of a case preceded by ocular trauma

Relatamos o caso de um paciente com cefaléia neuralgiforme unilateral de curta duraçao associada a hiperemia conjuntival e lacrimejamento ipsiloterais (sindrome de S.U.N.C.T.) precedida de trauma ocular ipsolateral. Nao encontramos na literatura associaçao similar. Até que a fisiopatologia da S.U.N.C.T. seja esclarecida, nao podemos definir se houve relaçao causal entre o trauma e a síndrome ou se sao epifenômenos.

Valor diagnóstico y terapéutico de la biopsia conjuntival en las enfermedades inflamatorias oculares externas / The conjunctival biopsy is an important role in the inflammatory processes the external structures of the eye

La conjuntiva desempeña un papel muy importante en los procesos inflamatorios de las estructuras oculares externas, incluyendo a la misma conjuntiva, la córnea y la esclera. La quetoconjuntivitis cicatrizante crónica representa un grupo de enfermedades con manifestaciones clínicas similares, pero con un diagnóstico diferencial muy extenso y en el cual la confirmación diagnóstica por medio de los hallazgos inmunohistopatológicos de la conjuntiva es de crucial importancia para instituir un tratamiento adecuado. Lo mismo es cierto para la queratitis ulcerativa periférica y la excleritis necrotizante, en las cuales la historia clínica detalla, en conjunto con la biopsia conjuntival, representan las dos armas diagnósticas fundamentales. Además, esta última es el punto crítico en la toma de decisiones respecto a si instituir o no quimioterapia inmunosupresiva en estos casos. De esta manera, el estudio histopatológico e inmunopatológico de la conjuntiva representa una arma fundamental en el diagnóstico, en el tratamiento, así como en el entendimiento de la patogénesis de las enfermedades inflamatorias oculares externas de origen inmunológico.

Microbiota fúngica conjuntival de pacientes com síndrome da imunodeficiência adquirida (AIDS) / Conjuncatival fungal microbiota in patients with acquired imunodeficiency syndrome (AIDS)

O número crescente de infecçäo por fungos em pacientes com Sídrome da Imunodeficiência Adquirida tem incentivado novos estudos sobre o envolvimento desses agentes nas patologias oculares e/ou sistêmicas. A escassez de dados referentes à flora micótica ocular em portadores de AIDS motivou a presente pesquisa, cuja finalidade foi analisar a microbiota fúngica conjuntival nos aidéticos. Foram examinados 85 pacientes com AIDS, internados por apresentarem alguma infecçäo oportunista sistêmica e/ou neoplasia e 60 indivíduos sadios, HIV negativos, para controle. Todos os pacientes examinados neste estudo eram moradores de área urbana de Säo Paulo e näo apresentavam quaisquer sintomas ou sinais de comprometimento ocular, no momento da colheita. Amostras do fornix inferior foram colhidas com cefanetes estéreis de ambos os olhos, de cada paciente e semeadas em meios de ágar-Sabouraud-dextrose com gentamicina. Os fungos isolados no grupo dos aidéticos foram: C. albicans, C. pseudotropicalis, C. glabrata, Cladosporium sp e Penicillium spp, enquanto no grupo dos individuos normais obteve-se os seguintes fungos: Cladosporium spp, M. sterilia, Acremonium sp, Fusarium sp e Candida sp