Prospective evaluation of a new intense pulsed light, thermaeye plus, in the treatment of dry eye disease due to meibomian gland dysfunction

Purpose: This study aims to estimate the efficacy and safety of a new intense pulsed light (IPL) Thermaeye Plus for dry eye disease (DED) secondary to meibomian gland dysfunction (MGD).Patients and methods: This is a prospective, longitudinal study of patients with moderate to severe MGD. Treatment consisted of 4 consecutive IPL sessions, 12 flashes with the same energy 8J/cm2 on the periocular area at days 1, 14, 28, and 49. All patients were evaluated before each IPL sessions and 1 and 4 months after the last session. Measuring: Symptoms score and OSDI questionnaire, Non-invasive tear meniscus height (NITMH), Non-invasive break up (NITBUT), Tear osmolarity (TO), Corneal fluorescein staining (CFS) and Eyelid margin and Meibomian gland assessment. The adverse effects on the eye, periocular area, and systemic complications were evaluated. All types of skin pigmentation (Fitzpatrick scale I to VI) were included. Results: The study included 44 consecutive patients (88 eyes), 40 males and 48 females, with a mean age of 52.5±13.6 years, ranging from 22 to 78 years. Significant improvements were observed in single and total signs and symptoms. The most significant changes were observed in dryness, foreign body sensation (p<0.001), and pain (p<0.005). The OSDI questionnaire showed a significant decrease in total symptoms (p<0.003). The percentage of patients with a normal index <13, improved from 23.8% (10 patients) at baseline to 80.9% (34 patients) at last visit, after 23 weeks. Clinical sings also improved, more than 90%, stand out telangiectasia and blepharitis (p<0.002, and p<0.0005, respectively). No statistical differences between age (<40y, 40–60y, and >60y) and gender were observed. The clinical improvement began after the second and third week after the first IPL session, until the end of the IPL treatment (D49). After that, the results maintained stable until the last visit, after 11 weeks. ... (AU)

Evaluation of ocular surface impairment in meibomian gland dysfunction of varying severity using a comprehensive grading scale.

This study aimed to propose a comprehensive grading scale to evaluate different clinical manifestations in patients with varying severity of meibomian gland dysfunction (MGD) and analyze the correlations between the parameters of ocular surface impairment in MGD.A total of 63 patients with MGD were enrolled. Ten specific symptoms were evaluated each with a subjective score and total score was applied to grade the severity of MGD. Thirty-seven patients were diagnosed with mild, 19 with moderate, and 7 with severe MGD. Slit-lamp and keratography were used to assess the signs of ocular surface and meibomian gland (MG). In vivo confocal microscopy (IVCM) was performed to evaluate the corneal nerves and dendritic cells. The differences and correlations between symptoms, signs, and IVCM parameters were analyzed.Dryness, foreign body sensation, asthenopia, and photophobia were the most common and severe symptoms in our patients. The severe MGD group showed worse MG expressibility, Meibum score, Meiboscore, MG score, and higher nerve reflectivity (P < .05). The mild MGD group showed higher nerve density (P < .05). Total symptom score was negatively correlated with nerve density (r = -0.374, P < .05), while positively correlated with nerve reflectivity and dendritic cell density (r = 0.332 and 0.288, respectively, P < .05). MG score was correlated with nerve reflectivity (r = 0.265, P < .05).The comprehensive grading scale was suitable for evaluating clinical manifestations in MGD of varying severity. The relationship between the specific symptoms, signs, and IVCM results concerning whole ocular surface impairment could help elucidate MGD pathophysiology and benefit evaluation or treatment in the future.

Colgajos o injertos cutáneos para la corrección de defectos palpebrales de gran tamaño / Flaps or cutaneous grafts for the correction of large eyelid defects

Objetivo: Describir los resultados estéticos y funcionales con el uso de colgajos o injertos cutáneos en la corrección de defectos palpebrales de gran tamaño. Métodos: Se realizó un estudio observacional, descriptivo, prospectivo, de 15 pacientes con lesiones tumorales o cicatrizales que provocaron defectos palpebrales de gran tamaño, desde enero a diciembre del año 2016, en la Consulta de Oculoplastia del Instituto Cubano de Oftalmología Ramón Pando Ferrer. Resultados: El 73,3 por ciento de los pacientes fue del sexo masculino y mayores de 60 años. Las lesiones tumorales representaron el 73,3 por ciento y el carcinoma basal el 53,3 por ciento. El párpado inferior fue el más comprometido. En el 60 por ciento de los casos se realizó colgajo cutáneo; de ellos, a 8 pacientes (88,8 por ciento) de tipo Tenzel. En el 73,3 por ciento de los pacientes no se presentaron complicaciones. El hematoma posquirúrgico fue la complicación general más frecuente (25 por ciento). Conclusiones: Los defectos palpebrales de gran tamaño se presentan en mayor cantidad en los pacientes mayores de 60 años, del sexo masculino. Predomina el carcinoma basal en el párpado inferior. La técnica reconstructiva con colgajos e injertos cutáneos resulta efectiva en la mayoría de los casos y se reporta un mínimo de complicaciones(AU)

Objective: To describe the esthetic and functional results of the use of flaps or cutaneous grafts for the correction of large eyelid defects. Method: A prospective, descriptive and observational study of 15 patients with tumoral or scar lesions that caused large eyelid defects was conducted from January to December, 2016 in the Oculoplasty Service of Ramon Pando Ferrer Cuban Institute of Ophthalmology. Results: In the study, 73.3 percent of patients were males aged over 60 years. Tumoral lesions were present in 73.3 percent of patients whereas basal carcinoma was found in 53.3 percent. The lower eyelid was the most affected. Sixty percent of cases were corrected with cutaneous flap, eight of them (88.8 percent) with Tenzel-type flap. No complications were seen in 73.3 percent of patients. Postsurgical hematoma was the most common complication (25 percent). Conclusions: Large eyelid defects were observed in a higher number of male patients aged 60 years. Basal carcinoma in the lower eyelid predominated. The reconstructive technique using flaps or cutaneous grafts proved to be effective in most of the cases, with minimal complications(AU)

Anquilobléfaron y el tratamiento a las anomalías congénitas palpebrales y del ojo / Ankyloblepharon and the treatment of congenital palpebral and ocular anomalies

El anquilobléfaron es la fusión parcial o total de los bordes palpebrales. En dependencia de la localización, este puede clasificarse como medial o interno y lateral o externo. Es una malformación congénita que constituye una condición muy infrecuente. Puede estar genéticamente determinada, aunque su causa exacta o mecanismo de producción no se conoce claramente. El primer caso corresponde a una lactante femenina, de 57 días de nacida, antecedentes de madre con paladar hendido ya operado. Al examen oftalmológico se constata en el ojo derecho fusión a nivel de todo el borde palpebral y en el izquierdo brida hacia sector temporal, además de presentar paladar hendido. El segundo caso, es una paciente femenina de 24 meses de edad, que en el examen ocular se observa brida que fusiona ambos bordes palpebrales del ojo izquierdo, en zona temporal. Se confirma diagnóstico de anquilobléfaron. En el primer caso se decide, por la edad, mantener una conducta expectante y posponer el tratamiento quirúrgico hasta que se realice la cirugía de la fisura labial, la cual se realiza a los 3 meses. En ambos casos la conducta fue quirúrgica, con buenos resultados estéticos y funcionales. El diagnóstico de esta anomalía es clínico y el examen físico minucioso, el cual, unido a los conocimientos del especialista sobre estas anomalías, juega un papel primordial. El tratamiento siempre es quirúrgico, el procedimiento a ejecutar es sencillo, incluso cuando requiere de reconstrucción palpebral(AU)

Ankyloblepharon is the partial or total fusion of eyelid margins. According to its location, it may be classified as medial or internal and lateral or external. This congenital malformation is a very rare condition. Though it may be genetically determined, its exact cause or development mechanism is not clearly known. The first case is a 57-day-old female infant whose mother had undergone cleft palate surgery. Ophthalmological examination revealed fusion of the entire eyelid margin of the right eye and bridling toward the temporal sector of the left eye, as well as a cleft palate. The second case is a 24-month-old female patient whose ophthalmological examination revealed bridling fusing the two eyelid margins of the left eye in the temporal zone. Ankyloblepharon diagnosis was confirmed. In the first case, due to the patient's age it was decided to postpone surgical treatment until lip fissure surgery was performed at 3 months. In both cases management was surgical, with good esthetic and functional results. Diagnosis of this condition is based on meticulous clinical and physical examination, supported by the decisive role played by the specialist's knowledge about these anomalies. Treatment is always surgical and the procedure to be performed is simple, even when palpebral reconstruction is required(AU)

Anquilobléfaron y el tratamiento a las anomalías congénitas palpebrales y del ojo / Ankyloblepharon and the treatment of congenital palpebral and ocular anomalies

El anquilobléfaron es la fusión parcial o total de los bordes palpebrales. En dependencia de la localización, este puede clasificarse como medial o interno y lateral o externo. Es una malformación congénita que constituye una condición muy infrecuente. Puede estar genéticamente determinada, aunque su causa exacta o mecanismo de producción no se conoce claramente. El primer caso corresponde a una lactante femenina, de 57 días de nacida, antecedentes de madre con paladar hendido ya operado. Al examen oftalmológico se constata en el ojo derecho fusión a nivel de todo el borde palpebral y en el izquierdo brida hacia sector temporal, además de presentar paladar hendido. El segundo caso, es una paciente femenina de 24 meses de edad, que en el examen ocular se observa brida que fusiona ambos bordes palpebrales del ojo izquierdo, en zona temporal. Se confirma diagnóstico de anquilobléfaron. En el primer caso se decide, por la edad, mantener una conducta expectante y posponer el tratamiento quirúrgico hasta que se realice la cirugía de la fisura labial, la cual se realiza a los 3 meses. En ambos casos la conducta fue quirúrgica, con buenos resultados estéticos y funcionales. El diagnóstico de esta anomalía es clínico y el examen físico minucioso, el cual, unido a los conocimientos del especialista sobre estas anomalías, juega un papel primordial. El tratamiento siempre es quirúrgico, el procedimiento a ejecutar es sencillo, incluso cuando requiere de reconstrucción palpebral(AU)

Ankyloblepharon is the partial or total fusion of eyelid margins. According to its location, it may be classified as medial or internal and lateral or external. This congenital malformation is a very rare condition. Though it may be genetically determined, its exact cause or development mechanism is not clearly known. The first case is a 57-day-old female infant whose mother had undergone cleft palate surgery. Ophthalmological examination revealed fusion of the entire eyelid margin of the right eye and bridling toward the temporal sector of the left eye, as well as a cleft palate. The second case is a 24-month-old female patient whose ophthalmological examination revealed bridling fusing the two eyelid margins of the left eye in the temporal zone. Ankyloblepharon diagnosis was confirmed. In the first case, due to the patient's age it was decided to postpone surgical treatment until lip fissure surgery was performed at 3 months. In both cases management was surgical, with good esthetic and functional results. Diagnosis of this condition is based on meticulous clinical and physical examination, supported by the decisive role played by the specialist's knowledge about these anomalies. Treatment is always surgical and the procedure to be performed is simple, even when palpebral reconstruction is required(AU)

Infrared meibography and molecular assessment of p63 gene mutations in a Mexican patient with EEC syndrome. / Meibografía infrarroja y evaluación molecular de la mutación del gen p63 en un paciente mexicano con síndrome EEC.

OBJECTIVE: To report the finding of infrared meibography in a Mexican patient with EEC syndrome (Ectrodactyly-ectodermal dysplasia-cleft syndrome) confirmed by molecular analysis of the p63 gene. CLINICAL CASE: A 31 year-old male patient was seen due to a history of progressive visual loss in both eyes associated with long-term photophobia. The patient was born with cleft lip and palate, ectrodactyly of right hand, and afterwards, displayed nail dysplasia, anodontia and alopecia, with which ectodermal dysplasia was diagnosed. The ophthalmological findings were limited to the adnexa and the ocular surface. In vivo infrared meibography showed total absence of Meibomian glands in the lower eyelids and severe deficiency in the upper eyelids. In addition, it was shown that the patient was a heterozygous carrier of a missense mutation R304W (C → T) in exon 8 of the p63 gene. DISCUSSION: The R304W mutation in the p63 gene region is definitely related to characteristics such as the absence of Meibomian glands.

Meibomian Gland Absence Related Dry Eye in Ectodysplasin A Mutant Mice.

Meibomian gland dysfunction is the most frequent cause of evaporative dry eye, yet its underlying pathophysiology is unknown. To gain insight into this pathophysiology, we characterized the time-dependent tear film and ocular surface changes occurring in X-linked anhidrotic-hypohidrotic ectodermal dysplasia mice (Tabby), which lack the meibomian gland. These mice sequentially developed corneal epithelial defects, central corneal stromal edema, neovascularization, and pannus 8 to 16 weeks after birth. Aqueous tear secretion was normal, whereas tear break-up time and ex vivo tear evaporation times were all shortened. Corneal epithelial microvilli were less numerous, conjunctival goblet cell density was unaffected, and MUC5AC and MUC5B gene expression was increased. Markers of squamous metaplasia (cytokeratin 10 and small proline-rich protein 1B) were noticed in the corneal epithelium of Tabby mice as early as the fourth week. Taken together, the Tabby mouse is a relevant meibomian gland dysfunction-related dry eye model that may lead to a better understanding of how meibomian glands are related to ocular surface health. This model may also help with discovering novel drug options for treating evaporative dry eye.

Perturbed meibomian gland and tarsal plate morphogenesis by excess TGFα in eyelid stroma.

Transforming growth factor alpha (TGFα) belongs to the epidermal growth factor (EGF) family and is known to play an important role during eyelid morphogenesis. In this study, we showed that ectopic expression of TGFα in the stroma of Kera-rtTA/tet-O-TGFα bitransgenic mice results in precocious eye opening, abnormal morphogenesis of the meibomian gland, tendon and tarsal plate malformation and epithelium hyperplasia. TGFα did not change proliferation and differentiation of meibocytes, but promoted proliferation and inhibited differentiation of the tarsal plate tenocytes. These results suggest that proper formation of the tendon and tarsal plate in the mouse eyelid is required for normal morphogenesis of the meibomian gland.

Estudio descriptivo sobre el carcinoma basocelular en el párpado / Descriptive study on basal cell eyelid carcinoma

OBJETIVO: Describir la presentación y características del carcinoma basocelular en los párpados. MATERIAL Y MÉTODOS: Se realiza un estudio retrospectivo a través de la revisión de historias clínicas, resultados anatomopatológicos y fotografías de 200 pacientes consecutivos con carcinoma basocelular palpebral intervenidos en la clínica oftalmológica Herzog Carl Theodor de Múnich, Alemania, entre los años 2000 y 2013. RESULTADOS: En el presente estudio las mujeres se afectan de forma más frecuente. La edad media son los 70 años. La afectación del párpado inferior se presenta en la mitad de los casos, siendo especialmente frecuente en el tercio central. El 47% de los carcinomas estudiados afectan al margen palpebral. El diámetro promedio es de 9,2 mm. El porcentaje de recidivas tras cirugía con márgenes limpios es del 5%. Estadísticamente se encuentran correlaciones significativas, de tal forma que, a mayor diámetro de la lesión mayor edad del paciente; los tumores aparecen con mayores tamaños a medida que se alejan de la zona medial y se acercan al margen del párpado. CONCLUSIONES: Existe un predominio de afectación en el sexo femenino; esto puede deberse a que la toma de la muestra pertenece a una consulta de cirugía oculoplástica. La aparición del carcinoma aumenta conforme avanza la edad. Existe una menor incidencia de basaliomas en el párpado superior que puede estar relacionada con la protección de la ceja frente a la luz solar. La mayor afectación del párpado inferior puede estar relacionada con un efecto de reflexión de la luz por la córnea hacia dicho párpado. Otra teoría se basa en el daño químico y físico producido por la concentración lagrimal. Los pacientes acuden a consulta de forma más precoz en edades más tempranas, si son mujeres, si se trata de tumores más cercanos a la zona medial y cuando hay mayor lejanía del margen palpebral

OBJECTIVE: To describe a series of cases of basal cell carcinomas of the eyelid. METHODS: A descriptive and retrospective study was conducted by reviewing the medical outcome, histopathological history, and photographic images of 200 patients with basal cell eyelid carcinomas. All were treated in the Herzog Carl Theodor Eye Hospital in Munich, Germany, between 2000 and 2013. RESULTS: In the present study, it was found that females are more affected than males. The mean age of presentation of the tumor occurred at the age of 70 years. In 50% of the cases the tumor was found on the lower lid, especially medially from the center of the lid. The lid margin was involved in 47% of all tumors. The mean diameter was 9.2 mm. The recurrence rate after surgery with histologically clear resection margins was 5%. There was a significant relationship between tumor diameter and age. As tumors where located farther away from medial and closer to the lid margin, they became larger. CONCLUSIONS: There is a predominance of women affected by this tumor. This may be related to the fact that the sample was taken from those attending an oculoplastic surgery clinic, where there are generally more women than men attending. The formation of basal cell carcinomas increases with age. The infrequent involvement of the upper lid could be explained by the protection of the the eyebrow. The frequent involvement of the lower lid may be due to the light reflection (total reflection) by the cornea on the lower lid margin. Also chemical and physical effects of the tears may be more harmful on the lower lid. Patients tend to ask for medical help when they are females, younger, when the tumor is closer to the medial canthus or when the tumor is away from the lid margin

Estudio comparativo de la eficacia de diversas modalidades terapéuticas en pacientes con blefaritis crónica / Comparative study of the efficacy of different treatment options in patients with chronic blepharitis

OBJETIVO: Comparar la eficacia de 3 modalidades de tratamiento en pacientes con blefaritis crónica. METODOLOGÍA: Se realizó un estudio experimental, aleatorizado y controlado en 45 pacientes (sexo femenino: 67%; edad media: 40,5 años) con diagnóstico de blefaritis crónica para comparar la eficacia de 3 modalidades de tratamiento. Grupo 1: higiene palpebral con champú neutro 3 veces/día; grupo 2: higiene palpebral con champú neutro y gel tópico de metronidazol al 0,75% 2 veces/día; grupo 3: higiene palpebral con champú neutro y pomada antibiótica de neomicina al 3,5% y polimixina al 10% con dexametasona al 0,5% 3 veces/día. Los síntomas y signos fueron valorados asignándoles puntuaciones entre 0: sin síntomas ni signos; 1: síntomas o signos leves; 2: síntomas o signos moderados y 3: síntomas o signos severos. RESULTADOS: En los 3 grupos de tratamiento se observó mejora significativa de los signos y síntomas. Mientras que los grupos 1 y 2 presentaron una mayor mejoría en todas las variables estudiadas (p < 0,05), el grupo 3 no presentó mejoría clínica para comezón (p = 0,16), ojo seco (p = 0,29), caída de pestañas (p = 0,16) ni eritema en el borde palpebral (p = 0,29). CONCLUSIÓN: La higiene palpebral con champú neutro y el uso combinado de champú neutro con gel de metronidazol reportaron mejores resultados que la higiene palpebral con champú neutro y pomada antibiótica de neomicina y polimixina con dexametasona

OBJECTIVE: To compare the efficacy of 3 treatment options in patients with chronic blepharitis. METHODOLOGY: An experimental, randomized, controlled study was conducted on 45 patients (female 67%; Mean age: 40.5 years) diagnosed with chronic blepharitis, in order to compare the effectiveness of three treatment options. Group 1: eyelid hygiene with neutral shampoo three times/day; group 2: neutral shampoo eyelid hygiene plus topical metronidazole gel 0.75% twice/day; group 3: neutral eyelid hygiene with shampoo plus neomycin 3.5% and polymyxin 10% antibiotic ointment with 0.5% dexamethasone 3 times/day. The symptoms and signs were assessed by assigning scores from 0: no symptoms and/or signs; 1: mild symptoms and/or signs, 2: moderate symptoms and/or signs; and 3: severe symptoms and/or signs. RESULTS: A significant improvement was observed in the signs and symptoms in all 3 treatment groups. While groups 1 and 2 had more improvement in all variables studied (P < .05), Group 3 showed no clinical improvement for itching (P = .16), dry eye (P = .29), eyelashes falling (P=.16), and erythema at the eyelid margin (P = .29). CONCLUSIONS: Shampoo eyelid hygiene neutral and neutral shampoo combined with the use of metronidazole gel reported better hygiene results than neutral shampoo lid with antibiotic ointment and neomycin and polymyxin dexamethasone

Sondaje intraductal de las glándulas de Meibomio para el tratamiento de blefaritis posterior severa / Intraductal meibomian gland probing for the treatment of blepharitis

OBJETIVO: Describir los resultados del sondaje intraductal de las glándulas de Meibomio como tratamiento de la blefaritis posterior severa. MÉTODOS: Estudio prospectivo, longitudinal, de pacientes con signos y síntomas de blefaritis posterior severa, los cuales fueron tratados con sondaje intraductal de las glándulas de Meibomio. Se incluyó a 16 pacientes, 62,5% femeninos y 32,5% masculinos, con diagnóstico de blefaritis posterior severa y se realizó el tratamiento en uno de los ojos. Se valoró el tiempo de rotura de la película lagrimal y, en una escala subjetiva del 0-10, mejoría subjetiva de la agudeza visual, molestia subjetiva al parpadeo y fotofobia, antes del procedimiento, a la semana y 6 meses después. RESULTADOS: El 100% de los pacientes mostró mejoría estadísticamente significativa en las 4 variables estudiadas a la semana y a los 6 meses. No se presentó ninguna complicación. DISCUSIÓN: La disfunción de las glándulas de Meibomio constituye una causa frecuente de consulta en oftalmología. Este estudio tuvo como objetivo describir los resultados obtenidos al realizar un sondaje intraductal, que mostró ser seguro y eficaz en el 100% de la muestra a los 6 meses. CONCLUSIONES: Podemos concluir en este estudio que el sondaje intraductal de las glándulas de Meibomio se trata de un procedimiento eficaz y prometedor para los que muestras resistencia al tratamiento conservador

OBJECTIVE: To describe the results of the meibomian gland probing as a treatment of severe posterior blepharitis. METHODS: Prospective, longitudinal study of patients with signs and symptoms of severe posterior blepharitis, who were treated with meibomian gland probing in Centro Oftalmológico Interlomas (CENOFI). A total of 16 patients were included, 62.5% female and 32.5% male, diagnosed with severe posterior blepharitis. Treatment was performed in one eye. The time of rupture of the tear film was evaluated, using a subjective scale of 0-10 photophobia, the improvement in pain and visual acuity was measured before the procedure, and at one week and 6 months after. RESULTS: All the patients showed a statistically significant improvement in all 4 variables al 6 months. There were no complications. DISCUSSION: The dysfunction of the meibomian glands is a common reason for ophthalmology consulting. The study describes the results obtained by performing an intraductal survey, which was shown to be safe and effective in 100% of the sample. CONCLUSIONS: It can be concluded from this study that meibomian gland probing is an effective and promising treatment for blepharitis resistant to conservative treatment

Conceptos actuales en la disfunción de las glándulas de Meibomio / Current concepts about the meibomian gland dysfunction

Los científicos han estado interesados en el estudio de las secreciones de las glándulas de Meibomio desde hace muchos años. Enfermedades asociadas, como los cánceres y la blefaritis posterior, se han observado en la literatura médica, desde la primera parte del siglo XX. Sin embargo, el término disfunción de las glándulas de Meibomio fue introducida por Korb y Henríquez en 1980. No existía una definición establecida publicada en la literatura hasta que más de 50 expertos internacionales participaron en un taller, que tuvo lugar durante un período de dos años, donde se llegó a definir como una anormalidad crónica y difusa de estas glándulas, comúnmente caracterizada por la obstrucción del conducto terminal y cambios cualitativos/cuantitativos en la secreción de esta. Esto puede resultar en la alteración de la película lagrimal, síntomas de irritación ocular, inflamación clínicamente aparente y enfermedad de la superficie ocular. Es en el mismo Taller Internacional, donde se decide clasificar de acuerdo con los cambios anatómicos, fisiopatológicos, o la gravedad de la enfermedad, donde la forma obstructiva fue la más generalizada. Constituye una afección frecuente con disminución de la calidad de vida y perjuicios potencialmente graves para el bienestar humano(AU)

Scientists have been interested in the study of secretions from meibomian glands for many years. Related illnesses as cancer and posterior blepharitis have been found in the medical literature since the first half of the 20th century. However, the term meibomian gland dysfunction was introduced by Korb and Henríquez in 1980. There was not a set definition published in the literature until over 50 international experts participated in a workshop held for 2 years. It was there where this disorder was finally defined as a chronic diffuse anomaly occurred in these glands, which is generally characterized by obstructed terminal duct and qualitative/ quantitative changes in the gland secretion. This may cause altered lachrymal film, ocular irritation symptoms, clinically apparent inflammation and ocular surface disease. In the same international workshop, it was decided to classify meibomian gland dysfunction according to the anatomical, physiopathological changes or to the severity of the disease, being the obstructive type the most generalized form. This is a frequent illness that reduces the quality of life and causes potentially serious damages for the human wellbeing(AU)

Conceptos actuales en la disfunción de las glándulas de meibomio / Current concepts about the meibomian gland dysfunction

Los científicos han estado interesados en el estudio de las secreciones de las glándulas de Meibomio desde hace muchos años. Enfermedades asociadas, como los cánceres y la blefaritis posterior, se han observado en la literatura médica, desde la primera parte del siglo XX. Sin embargo, el término "disfunción de las glándulas de Meibomio" fue introducida por Korb y Henríquez en 1980. No existía una definición establecida publicada en la literatura hasta que más de 50 expertos internacionales participaron en un taller, que tuvo lugar durante un período de dos años, donde se llegó a definir como una anormalidad crónica y difusa de estas glándulas, comúnmente caracterizada por la obstrucción del conducto terminal y cambios cualitativos/cuantitativos en la secreción de esta. Esto puede resultar en la alteración de la película lagrimal, síntomas de irritación ocular, inflamación clínicamente aparente y enfermedad de la superficie ocular. Es en el mismo Taller Internacional, donde se decide clasificar de acuerdo con los cambios anatómicos, fisiopatológicos, o la gravedad de la enfermedad, donde la forma obstructiva fue la más generalizada. Constituye una afección frecuente con disminución de la calidad de vida y perjuicios potencialmente graves para el bienestar humano.

Scientists have been interested in the study of secretions from meibomian glands for many years. Related illnesses as cancer and posterior blepharitis have been found in the medical literature since the first half of the 20th century. However, the term «meibomian gland dysfunction¼ was introduced by Korb and Henríquez in 1980. There was not a set definition published in the literature until over 50 international experts participated in a workshop held for 2 years. It was there where this disorder was finally defined as a chronic diffuse anomaly occurred in these glands, which is generally characterized by obstructed terminal duct and qualitative/quantitative changes in the gland secretion. This may cause altered lachrymal film, ocular irritation symptoms, clinically apparent inflammation and ocular surface disease. In the same international workshop, it was decided to classify meibomian gland dysfunction according to the anatomical, physiopathological changes or to the severity of the disease, being the obstructive type the most generalized form. This is a frequent illness that reduces the quality of life and causes potentially serious damages for the human wellbeing.

Ocular and skin manifestations in systemic pseudohypoaldosteronism.

Pseudohypoaldosteronism type-1 is a rare disorder characterised by end-organ resistance to aldosterone resulting in salt-losing crisis with hyponatraemic dehydration, hyperkalaemia and metabolic acidosis. We report two siblings with pseudohypoaldosteronism type-1 who presented early in neonatal period with hyponatraemia, severe hyperkalaemia and metabolic acidosis. Both babies had miliaria like skin rash which flared up during episodes of hyperkalaemia and hyponatraemia. They had visible dilated meibomian glands from which a white material was protruding. The clinical presentation of pseudohypoaldosteronism type-1 mimics congenital adrenal hyperplasia. As there is often a delay in obtaining hormonal assay results, the eye and skin manifestations may give an important diagnostic clue which in turn will influence management.

Waved with open eyelids 2 (woe2) is a novel spontaneous mouse mutation in the protein phosphatase 1, regulatory (inhibitor) subunit 13 like (Ppp1r13l) gene.

BACKGROUND: Waved with open eyelids 2 (woe2) is a novel autosomal recessive mouse mutation that arose spontaneously in our animal facility. Upon initial evaluation, mutant mice exhibited eyelids open at birth (EOB) and wavy fur phenotypes. The goals of this study were to phenotypically characterize the woe2 mice and to identify the gene harboring the mutation responsible for the woe2 phenotype. RESULTS: Histological analysis of woe2 embryos identified the failure of embryonic eyelid closure. Clinical and histological analysis of woe2 adult eyes identified severe corneal opacities, abnormalities of the anterior segment of the eye, and the absence of meibomian glands. Abnormalities in the fur texture and the absence of meibomian glands prompted us to evaluate other epidermal appendages: skin, teeth, and nails--as well as lacrimal, mammary, salivary, sebaceous and sweat glands. No obvious morphological differences between WT and woe2 mice were identified in these tissues. However, the analysis of woe2 identified cardiac abnormalities. Positional cloning of the woe2 locus identified a 1308 bp deletion in the Ppp1r13l gene. The deletion resulted in an aberrant Ppp1r13l(Δexon9-11) transcript that lacks exons 9, 10 and 11 resulting in a premature stop and a loss of 223 amino acids from the C-terminal end of the putative mutant PPP1R13L protein. Immunohistological analysis during eye development identified expression of PPP1R13L in the palpebral epidermis, palpebral and bulbar conjunctiva, corneal epithelium and meibomian glands. CONCLUSIONS: The woe2 mouse harbors a novel deletion within the Ppp1r13l gene, likely resulting in a complete loss of PPP1R13L function. Results from this study provide evidence that PPP1R13L has an essential role in embryonic eyelid closure as well in development of meibomian glands and the anterior segment of the eye. The woe2 mice are a useful model for investigation of the role of PPP1R13L, especially during ocular and eyelid development.

Conditional disruption of mouse Klf5 results in defective eyelids with malformed meibomian glands, abnormal cornea and loss of conjunctival goblet cells.

Members of the Krüppel-like family of transcription factors regulate diverse developmental processes in various organs. Previously, we have demonstrated the role of Klf4 in the mouse ocular surface. Herein, we determined the role of the structurally related Klf5, using Klf5-conditional null (Klf5CN) mice derived by mating Klf5-LoxP and Le-Cre mice. Klf5 mRNA was detected as early as embryonic day 12 (E12) in the cornea, conjunctiva and eyelids, wherein its expression increased during development. Though the embryonic eye morphogenesis was unaltered in the Klf5CN mice, postnatal maturation was defective, resulting in smaller eyes with swollen eyelids that failed to separate properly. Klf5CN palpebral epidermis was hyperplastic with 7-9 layers of keratinocytes, compared with 2-3 in the wild type (WT). Klf5CN eyelid hair follicles and sebaceous glands were significantly enlarged, and the meibomian glands malformed. Klf5CN lacrimal glands displayed increased vasculature and large number of infiltrating cells. Klf5CN corneas were translucent, thicker with defective epithelial basement membrane and hypercellular stroma. Klf5CN conjunctiva lacked goblet cells, demonstrating that Klf5 is required for conjunctival goblet cell development. The number of Ki67-positive mitotic cells was more than doubled, consistent with the increased number of Klf5CN ocular surface epithelial cells. Co-ablation of Klf4 and Klf5 resulted in a more severe ocular surface phenotype compared with Klf4CN or Klf5CN, demonstrating that Klf4 and Klf5 share few if any, redundant functions. Thus, Klf5CN mice provide a useful model for investigating ocular surface pathologies involving meibomian gland dysfunction, blepharitis, corneal or conjunctival defects.

Choroideremia in a woman with ectodermal dysplasia and complex translocations involving chromosomes X, 1, and 3.

BACKGROUND: Choroideremia is an X-linked recessive disorder characterized by vision loss with progressive atrophy of the retinal photoreceptors, retinal pigment epithelium (RPE), and choriocapillaris. Ectodermal dysplasia is a heterogeneous group of disorders characterized by a deficiency of two or more ectodermal derivatives. We report on the phenotypic and genetic characteristics of a 29-year-old woman with both choroideremia and ectodermal dysplasia. MATERIALS AND METHODS: Observational case report with physical and ophthalmic examination, fluorescein angiography (FA), visual field testing, electroretinography, and cytogenetic analysis. This study adhered to the tenets of the Declaration of Helsinki and The New York Eye and Ear Infirmary Institutional Review Board guidelines. RESULTS: Physical and ocular examination revealed hypotrichosis, hypohidrosis, full dentures, meibomian gland hypoplasia, and a decrease in corneal tear film. Visual acuity was hand motions in the right eye and 20/50 in the left eye. Fundus examination and fluorescein angiography were consistent with advanced choroideremia and revealed diffuse bilateral RPE and chorioretinal atrophy with sparing of the fovea. Visual field testing had less than 10-degree central islands in both eyes. Scotopic electroretinogram (ERG) was flat with a small flicker response. Cytogenetic analysis showed a complex translocation involving chromosomes X, 1, and 3: 46,X,t(X;1;3)(q13;q24;q21),inv(9)(p11q13). Selective inactivation of the normal X chromosome was present in blood and skin. Chromosomal analyses of the proband's family (mother and two brothers) were normal. CONCLUSION: An X-autosome chromosomal translocation combined with non-random inactivation of the normal X-chromosome in a woman resulted in the phenotypic findings of choroideremia and ectodermal dysplasia.

Management of evaporative dry eye in ectrodactyly-ectodermal dysplasia-clefting syndrome.

PURPOSE: The purpose of this study is to report the features of dry eye and ocular surface disease in an unusual case of ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome. CASE REPORT: A single observational case report of a 22-year-old Japanese male with evaporative dry eye and corneal epithelial disease because of lipid layer abnormality resulting from meibomian gland agenesis was treated successfully with low dose lipid base ointment application. DISCUSSION: The clinical features of the dry eye and ocular surface disease and management issues are discussed. CONCLUSION: Low dose lipid base ointment application may be a promising treatment modality for the ocular surface disease in ectrodactyly-ectodermal dysplasia (EEC)-clefting syndrome, which seems to help in alleviating the subjective complaints and in improving the objective clinical findings.

Corneal epithelial cell fate is maintained during repair by Notch1 signaling via the regulation of vitamin A metabolism.

Integrity and preservation of a transparent cornea are essential for good vision. The corneal epithelium is stratified and nonkeratinized and is maintained and repaired by corneal stem cells. Here we demonstrate that Notch1 signaling is essential for cell fate maintenance of corneal epithelium during repair. Inducible ablation of Notch1 in the cornea combined with mechanical wounding show that Notch1-deficient corneal progenitor cells differentiate into a hyperplastic, keratinized, skin-like epithelium. This cell fate switch leads to corneal blindness and involves cell nonautonomous processes, characterized by secretion of fibroblast growth factor-2 (FGF-2) through Notch1(-/-) epithelium followed by vascularization and remodeling of the underlying stroma. Vitamin A deficiency is known to induce a similar corneal defect in humans (severe xerophthalmia). Accordingly, we found that Notch1 signaling is linked to vitamin A metabolism by regulating the expression of cellular retinol binding protein 1 (CRBP1), required to generate a pool of intracellular retinol.