Autologous serum eyedrops in the treatment of aniridic keratopathy.

OBJECTIVE: To study the effect of autologous serum eyedrop application in aniridic keratopathy. DESIGN: Prospective, consecutive, comparative, interventional case series. PARTICIPANTS: Twenty-six eyes from 13 patients (7 males and 6 females) with aniridic keratopathy treated with autologous serum eyedrops. METHODS: All patients underwent a complete ophthalmic examination. The ocular surface examinations included corneal impression cytologic analysis and tear film evaluation. The eyes were divided into 4 groups according to the Mackman classification. Ocular surface photography was used to evaluate the corneal surface and tear film before treatment and every 2 or 3 days until serum drops were stopped. Tear films were evaluated by tear film break-up time (BUT) (normal, 10 seconds or more), Schirmer's test with anesthesia (normal, 10 mm/5 minutes or more), tear meniscus level (normal, 0.5 mm or more), and rose bengal and fluorescein staining pattern of the cornea. Impression cytologic analysis was carried out both before starting the serum eyedrops treatment and a few days after its finalization. MAIN OUTCOMES MEASURES: Tear film production and stability, corneal epithelialization, and corneal epithelium squamous metaplasia. RESULTS: There were no local side effects from autologous serum treatment. Clinical manifestations and slit-lamp findings were in relation to the severity of keratopathy. All patients showed a subjective improvement of keratopathy symptoms after the autologous serum applications. The corneal epithelialization, corneal epithelial cell squamous metaplasia, and tear stability improved significantly with the treatment, but visual acuity, regression of vascular pannus, and subepithelial scarring showed only slight improvement with treatment. CONCLUSIONS: Autologous serum eyedrops improved the aniridic keratopathy in all patients, particularly in patients with light or moderate severity. In these patients, use of autologous serum eyedrops was superior to conventional therapy with substitute tears for improving the ocular surface and subjective comfort.

Una discusión actual ¿grave o severo? / Grave or severe? A current discussion

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Different conjunctival adaptive response in patients with aqueous-deficient and with mucous-deficient dry eyes.

PURPOSE: To describe the different cellular adaptive patterns found in the conjunctival epithelium from patients with aqueous-deficient and mucous-deficient dry eyes. METHODS: The authors studied different conjunctival areas, by impression cytology and by biopsy, 50 eyes with facial nerve paralysis (FNP), 50 eyes with ocular cicatricial pemphigoid (OCP), and 50 eyes from patients with primarily Sjögren syndrome (1SS). RESULTS: Eyes with FNP from the first clinical grade showed a progressive alteration of the nonsecretory cells, with a significant decrease in density goblet cells, generally with a PAS-positive staining. Eyes with OCP, during clinical grades 1 and 2, showed a slow deterioration of the nonsecretory cells; but from clinical grade 3, there was a significant increase of the cellular size and the thickness of the conjunctiva. Goblet cells showed a significant decrease in density from clinical grade 1, generally with a PAS-negative staining. Eyes with 1SS during clinical grades 1 and 2 showed a progressive alteration of the nonsecretory cells, with a significant decrease in density goblet cells, and a PAS-positive staining. From clinical grade 3 appeared a significant increase of nonsecretory cellular size and thickness of conjunctiva, with a significant decrease in goblet cell counts, and a PAS-negative staining. CONCLUSIONS: Patients with FNP (a primarily aqueous-deficient alteration) follow completely the squamous metaplasia process. Patients with OCP (a primarily mucous-deficient syndrome) have a hypertrophy and hyperplasia process along the ocular surface. Patients with 1SS (a primarily aqueous-deficient and mucin-deficient alteration) have a squamous metaplasia process, but from clinical grade 3 also appears a hypertrophy and hyperplasia process.

Analysis of corneal surface evolution after moderate alkaline burns by using impression cytology.

PURPOSE: To compare corneal surface evolution after moderate alkaline burns by impression cytology in patients treated with medical therapy or with amniotic membrane transplantation (AMT). METHODS: A prospective study of 24 eyes from 18 patients (13 men and 5 women) with moderate alkaline burns was performed. All patients were divided according to the clinical ocular severity and the therapy used. Twelve eyes were treated surgically with AMT and the other 12 eyes received only medical therapy. Corneal cytology was obtained immediately after the burns, and 1, 2, 5, and 9 months later. We differentiated between samples obtained from affected areas and areas not affected by the burns. Cellular size, nuclear size, and nuclear-cytoplasmic (N:C) ratio were examined in corneal epithelial cells, as was the presence of goblet cells in corneal epithelium. RESULTS: Nuclear size, cellular size, and N:C ratio in non-burn-affected corneal areas had no significant alterations in comparison with normal eyes. In contrast, in burn-affected corneal areas, these parameters were significantly worse, and the presence of goblet cells in corneal epithelium was frequent 1 month after severe burns. Cellular size, nuclear size, N:C ratio, and corneal conjunctivalization improved during the study in all patients, but corneal reepithelialization occurred earlier in patients treated with AMT than in patients with only medical therapy. CONCLUSION: Morphologic and morphometric analysis of corneal cells by impression cytology after ocular burns permits the establishment of cellular reepithelialization patterns in relation with limbal deficiency level and with clinical ocular severity. AMT improves corneal reepithelialization earlier than medical therapy in moderate alkaline burns.

Phacoemulsification in previously vitrectomized patients: an analysis of the surgical results in 100 eyes as well as the factors contributing to the cataract formation.

PURPOSE: To evaluate the safety and effectiveness of phacoemulsification with clear corneal incision in previously vitrectomized patients as well as factors affecting the development time and type of cataract occurring after pars plana vitrectomy (PPV). METHODS: The authors conducted a prospective study of 100 consecutive eyes of patients who developed a cataract after PPV. Three groups were established based on the underlying vitreoretinal pathology. The main outcome measurements were intraoperative and postoperative complications and changes in best-corrected visual acuity (BCVA). RESULTS: The median interval between PPV and phacoemulsification was 11.5 months. Patients with proliferative diabetic retinopathy required phacoemulsification earlier (p=0.018). Posterior subcapsular cataracts developed more frequently in patients <50 years (73.7%, p=0.000) and affected those who underwent vitrectomy primarily for complicated retinal detachment (48.8%, p=0.046). Intraoperative complications included posterior capsular tears (4%), luxated nucleus into vitreous (2%), and zonular dialysis (5%). Postoperative complications were vitreous hemorrhage (6%), retinal redetachment (4%), pupillary synechiae (6%), ocular hypertension (4%), and Seidel phenomenon (3%). Posterior Nd:YAG laser capsulotomy was required in 44% of eyes. BCVA was improved in 85% of cases at the end of follow-up (median, 15.5 months). Twenty-one patients with one functioning eye (61.9%) demonstrated visual improvement compared with 79 patients with bilateral vision (91.1%; p=0.003). CONCLUSIONS: The technique allows stable improvement in BCVA through long follow-ups. It is more risky than in nonvitrectomized eyes. The visual results after phacoemulsification in vitrectomized eyes seem to be limited by retinal comorbidity and surgical complications.

The triple classification of dry eye for practical clinical use.

PURPOSE: "Dry Eye is a condition produced by the inadequate interrelation between lacrimal film and ocular surface epithelium, and is caused by quantitative and qualitative deficits in one or both of them. It can be produced by one or combined etiologic causes, affecting one or several of the secretions of the glands serving the ocular surface, and producing secondary manifestations of different grades of severity". Clinicians need a practical classification to face diagnosis, prognosis and treatment. Dry eyes have many etiologies and pathogenesis, different affectation of the various dacryoglands and ocular surface epithelium, and diverse grades of severity. The specialists in xero-dacryology must know these three parameters to evaluate any case of dry eye, and to establish an adequate treatment. METHODS: To facilitate this, an open session in the 8th congress of the International Society of Dacryology and Dry Eye (Madrid, April, 2005) proposed modifying the Triple Classification of dry eye approved in the XIV congress of the European Society of Ophthalmology (Madrid, June, 2003). There was consensus of all conclusions. CONCLUSIONS: The following classification has been established: First, a classification of the etio-pathogenesis, distributed in ten groups: age-related, hormonal, pharmacologic, immunopathic, hyponutritional, dysgenic, infectious/inflammatory, traumatic, neurologic and tantalic. Second, a classification of the affected glands and tissues, which under the acronym of ALMEN includes the Aqueo-serousdeficient, Lipodeficient, Mucindeficient and Epitheliopatic dry eyes, and the Non dacryological affected exocrine glands (saliva, nasal secretion, tracheo-pharyngeal secretion, etc). And thirdly, a classification of severity, in three grades: Grade 1 or mild (symptoms without slitlamp signs), grade 2 or moderate (symptoms with reversible signs), and grade 3 or severe (symptoms with permanent signs).

[The contribution of impression cytology towards the diagnosis of cicatricial ocular pemphigoid in its primary stages]. / Contribución de la citología de impresión al diagnóstico del penfigoide cicatricial ocular en sus primeras fases.

PURPOSE: To study the conjunctival epithelium by means of impression cytology in the cicatricial ocular pemphigoid (COP) in search of a possible relation between the degree of squamous metaplasia and clinical severity of the disease, in order to facilitate the earliest possible diagnosis. METHODS: Impression cytology specimens were collected from 20 patients with varying degrees of active COP. A clinical ophthalmologic examination was performed by biomicroscopy, impression cytology, conjunctival biopsy, study of direct (IFd) and of indirect immunofluorescence (IFi). RESULTS: Patients with COP grade I had a normal distribution of non-secretory epithelial cells with a decrease in goblet cell density of around 85% compared to control and mucin content was decrease. Patients with grade II showed a slight degree of squamous metaplasia. Goblet cell density decreased by around 95% and mucin content was scarce. Patients with clinical grade III had a moderate degree of squamous metaplasia in non-secretory cells whilst goblet cell density decreased by around 99%; mucin content was almost zero. Patients with clinical grade IV showed a moderate to severe degree of squamous metaplasia in non-secretory cells; there was a total absence of goblet cells. CONCLUSIONS: Conjunctival impression cytology in COP showed a significant decrease in goblet cells from the early stages of disease without significant alterations in non-secretory epithelial cells. In patients with negative IFd impression cytology could enable the identification of a possible COP.

Contribución de la citología de impresión al diagnóstico del penfigoide cicatricial ocular en sus primeras fases / The contribution of impression cytology towards the diagnosis of cicatricial ocular pemphigoid in its primary stages

Objetivos: Estudiar el epitelio de la superficie ocular mediante citología de impresión en el penfigoide cicatricial ocular (PCO), buscando la posible relación entre la metaplasia escamosa y la severidad clínica de la enfermedad, para facilitar el diagnóstico más temprano posible. Métodos: Participaron 20 pacientes con diferente grado clínico. El diagnóstico clínico se realizó mediante un estudio oftalmológico con la lámpara de hendidura, pruebas clínicas, citología de impresión, biopsia conjuntival, y estudio de inmunofluroscencia directa (IFd) e indirecta (IFi).Resultados: Los pacientes con grado clínico I tuvieron una superficie ocular formada por células no secretoras normales y por una disminución de células caliciformes del 85 por ciento respecto al control, con un contenido reducido de mucina. Los pacientes con grado clínico II mostraron una leve metaplasia escamosa de las células no secretoras. Las células caliciformes disminuyeron un 95 por ciento y el contenido de mucina fue muy escaso. Los pacientes con grado clínico III tuvieron una metaplasia escamosa moderada de las células no secretoras, mientras las células caliciformes disminuyeron hasta el 99 por ciento y estuvieron casi vacías. Los pacientes con grado clínico IV mostraron una metaplasia escamosa moderada-severa de las células no secretoras. Hubo ausencia de células caliciformes. Conclusiones: La citología de impresión en conjuntivas con PCO mostró una gran pérdida de células caliciformes desde las primeras fases de la enfermedad sin grandes alteraciones en las células epiteliales no secretoras. En pacientes con una IFd aún negativa, esta técnica puede indicar la existencia de un posible PCO, al poner de manifiesto una sequedad ocular mucodeficiente y sistémica (AU)

The Madrid triple classification of dry eye.

From the clinical point of view, there are many etiologic causes, several combinations of anatomo-pathologic manifestations, and different grades of severity of Dry Eye diseases in the dysfunctional tear film syndrome. The dacryologist doctor must recognize these three parameters, quantify them, and establish the most appropriate treatment. The present triple classification has been elaborated for this purpose. First, there is an etiologic distribution in ten groups: age-related, hormonal, pharmacologic, immunopathic, hyponutritional, dysgenetic, inflammatory, traumatic, neurodeprivative, and tantalic. Each of these groups comprise many variants. Second, there is an anatomo-pathologic classification named ALMEN classification from the acronym of aquodeficiency, lipodeficiency, mucodeficiency, epitheliopathy, and non-ocular exocrine affectations. Finally, there is a severity classification in five grades: subclinical (symptoms only when overexposure), mild (habitual symptoms), moderate (symptoms plus reversible signs), severe (symptoms plus permanent signs), and disabling (all the above, plus visual discapacity).

[Impression cytology study of dry eyes in patients with congenital aniridia]. / Estudio del ojo seco en pacientes con aniridia congénita, mediante citología de impresión.

PURPOSE: To evaluate the long-term results of ocular surface reconstruction by means of medical treatment, limbal transplantation or amniotic membrane transplantation in patients with congenital aniridia. MATERIAL AND METHODS: Thirty-six eyes from 18 consecutive patients with aniridia were studied by clinical tests (Schirmer test, break-up time and vital rose bengal staining) and impression cytology. Thirteen patients were treated with lubricant drops for ocular dryness. Two eyes from 2 patients also received limbal transplantation, and other 4 eyes underwent amniotic membrane transplantation. RESULTS: Corneal and conjunctival epithelium improved in all patients treated with lubricant drops. Ocular surface epithelium condition was worse in those patients not receiving artificial tears. After 12 months of limbal transplantation, clinical and morphological results showed a significant corneal recovery of at least two grades of squamous metaplasia in comparison with the previous situation. We also carried out amniotic membrane transplantation in patients with aniridia. The improvement was initially observed after 2 months and by the sixth month there was a significant improvement in clinical signs and symptoms, with normal corneal cells next to altered ones. CONCLUSIONS: All the aniridic patients showed dry eye. Treatment with lubricant drops is necessary to decrease the squamous metaplasia process. Limbal transplantation and amniotic membrane implantation are needed for effective corneal surface reconstruction in patients with aniridia, which is followed by a significant improvement of the dry eye.

Triple clasificación de Madrid para el ojo seco / The Madrid triple classification of dry eye

Desde el punto de vista del clínico, las enfermedades de Ojo Seco, incluidas en el síndrome de disfunción de la película lacrimal, tienen múltiples causas etiológicas, distintas combinaciones de afectaciones anatomopatológicas y diversos grados de gravedad. El médico dacriólogo debe conocer estos tres parámetros, cuantificarlos, y establecer sobre ellos el tratamiento oportuno. Para ello, se ha elaborado la presente clasificación clínica que en primer lugar incluye una clasificación etiológica en causas etarias, hormonales, farmacológicas, inmunopáticas, hiponutricionales, disgenéticas, inflamatorias, traumáticas, neurodeprivativas y tantálicas, incluyendo cada uno de estos grupos numerosas variantes. En segundo lugar, una clasificación histopatológica o ALMEN, acrónimo de acuodeficiencia, lipodeficiencia, mucodeficiencia, epiteliopatía y afectación de otras glándulas exocrinas no oculares. Y en tercer lugar, una clasificación de gravedad en cinco escalones: subclínico (síntomas en situaciones de sobreexposición), leve (síntomas habitualmente), moderada (síntomas y signos reversibles), grave (síntomas y signos irreversibles) e incapacitante (pérdida irreversible de visión por daño corneal) (AU)

Estudio del ojo seco en pacientes con aniridia congénita, mediante citología de impresión / Impression cytology study of dry eyes in patients with congenital aniridia

Objetivos: Evaluar la sequedad ocular en pacientes con aniridia congénita antes y después de la reconstrucción de la superficie ocular a largo plazo sometidos a un tratamiento médico, a un transplante limbal o a un implante de membrana amniótica. Material y Métodos: Se estudiaron 36 ojos pertenecientes a 18 pacientes consecutivos con aniridia congénita mediante pruebas clínicas (prueba de Schirmer, tiempo de ruptura de la película lagrimal y tinción vital con rosa de bengala) y la citología de impresión. Trece pacientes se trataron continuamente con lágrimas artificiales por sequedad ocular. En 2 ojos de 2 pacientes se añadió el transplante limbal y en otros 4 ojos de transplante de membrana amniótica a la córnea. Resultados: El epitelio corneal y conjuntival de todos los pacientes mejoró con el tratamiento médico de lágrimas artificiales. Los pacientes que no utilizaron lágrimas artificiales presentaron peor estado del epitelio de la superficie ocular. El transplante de limbo después de 12 meses mostró una recuperación corneal significativa, de al menos dos grados de metaplasia escamosa respecto a antes de la cirugía. El efecto clínico del implante de membrana amniótica empezó a notarse a los 2 meses de la intervención quirúrgica y al cabo de 6 meses hubo una mejoría significativa en los signos y síntomas clínicos, con la aparición de células epiteliales corneales prácticamente normales junto a otras aún alteradas. Conclusiones: Todos los pacientes con aniridia mostraron signos citológicos de ojo seco. El tratamiento con lagrimas artificiales es necesario en pacientes con aniridia para controlar el grado de metaplasia escamosa. El transplante limbal y el de membrana amniótica son necesarios para la reconstrucción efectiva de la superficie corneal en pacientes con aniridia, permitiendo a su vez que el ojo seco mejore significativamente (AU)

Biopsy of the conjunctiva in dry eye patients establishes a correlation between squamous metaplasia and dry eye clinical severity.

PURPOSE: The aim of this work was to evaluate the different grades of squamous metaplasia of the conjunctiva during the clinical course of dry eye syndrome, detecting the most characteristic morphological and morphometric changes by biopsy in order to provide a diagnostic classification. METHODS: The conjunctiva was studied under light microscopy by conventional histological methods and by morphometric analysis in 165 patients and in 33 controls. Patients were classified according to the Schirmer 1 test, break-up time, rose Bengal staining, osmolarity and impression cytology. The epithelium and connective tissue, with their different cells and other structures, were studied. RESULTS: The conjunctiva in dry eye patients showed progressive stratification, hyperplasia, hypertrophy and cellular flattening, with loss of goblet cell density and mucous layer. We found five pathological grades of squamous metaplasia and one normal grade. Clear nuclear alterations (indentation and binucleation) were found in the early grades of dry eye syndrome, but pyknotic nuclei and anucleated cells were only seen in the most severe grades. The smallest epithelial cells were found in the control group and their size increased with the severity of the dry eye syndrome. From the earliest stages to the most severe cases, increases in cellular separation were observed. There was also an increase in the number of inflammatory cells. Blood and lymphatic vessels showed alterations only in the most severe cases. CONCLUSIONS: This is the first grading system proposed for biopsy evaluation of the ocular surface in dry eye patients. These morphological and morphometric studies alone were able, even in the earliest phases of dry eye, to detect the squamous metaplasia that progresses from the surface of the epithelium to the connective tissue. This degenerative or adaptative cellular process was characterized mainly by marked increases in the stratification, epithelial cellular size and a general loss of goblet cells.

Impression cytology on conjunctiva and cornea in dry eye patients establishes a correlation between squamous metaplasia and dry eye clinical severity.

PURPOSE: To obtain deeper knowledge of the cellular transition in squamous metaplasia, and to look for a correlation between the clinical grade of severity of dry eye and the grade of squamous metaplasia of the corneal and conjunctival epithelium, studied by impression cytology. METHODS: A total of 143 patients with dry eye disorders of different grades of clinical severity and 33 control subjects of matched age and sex were studied. Symptoms, clinical tests (including Schirmer test, slit-lamp examination, break-up time, rose Bengal staining, vanishing lacunar sulci, and neovascularization), and tear osmolarity were used to establish the diagnosis of dry eye. The subjects were classified into six clinical grades, grade 0 indicating normal and grades 1 to 5 progressively more severe dry eye. Impression cytology specimens were taken from the central cornea and different areas of the conjunctiva of one eye from all patients. A morphologic and morphometric study of the photographs obtained by light microscopy showed cell size, nuclear size, nuclear-cytoplasmic ratio (N:C) in nonsecretory epithelial cells, and density of goblet cells. RESULTS: Morphometric and morphologic studies of the ocular surface cells indicated significant differences, mainly in cell sizes, nuclear alterations, and the N:C ratio, in nonsecretory epithelial cells of the conjunctiva and cornea, and in goblet cell densities from the conjunctiva, between the clinically normal eyes and those with the five grades of clinical severity of dry eye, with different degrees of squamous metaplasia. CONCLUSIONS: A morphologic and morphometric analysis of the ocular surface from patients with dry eye obtained by impression cytology led us to draft a new grading system containing one normal level and five levels of squamous metaplasia. This new grading system is based on a significant decrease in the number of goblet cells with less periodic acid-Schiff-hematoxylin-positive staining, an increase in nonsecretory cell size, more marked cell separation, a lower N:C ratio, and an increase in nuclear alterations. The clinical severity of the dry eye correlates with these alterations.

[Innervation of the lachrymal gland in patients with primary Sjögren's syndrome. An immunohistopathological study]. / Inervación de la glándula lagrimal en pacientes con síndrome de Sjögren primario. Estudio inmunohistopatológico.

PURPOSE: Histopathological parameters of the main lachrymal gland from patients with primary Sjögren's syndrome (SS1) were investigated, and the relation between morphological and immunohistochemical changes in the innervation of lachrymal gland in patients with SS1, as well as the immunopathological differences between SS1, non-autoimmune keratoconjunctivitis sicca (KCS) and controls were analysed. METHODS: Lachrymal glands from patients with SS1, KCS and control subjects were biopsied and examined using standard transmission electron microscopic techniques and an immunohistochemical method (vasoactive intestinal polypeptide-VIP). RESULTS: Moderate numbers of myelinated and non-myelinated nerve fibres were found in the connective tissue around lachrymal glands in patients with SS1. Non-myelinated nerve fibres made contact with glandular epithelium, myoepithelial cells, vascular endothelium, plasma cells and fibroblasts. Patients with non-immunological KCS had similar characteristics as SS1 in number and activity, showing a normal morphological pattern. Control subjects showed a higher number of active nerve fibres. CONCLUSION: Main lachrymal gland from patients with SS1 were therefore definitively innervated with moderate activity and normal structures. The ultrastructural study demonstrated there were no statistical differences with respect to patients with non-autoimmune KCS. Immunohistochemical studies showed a similar VIP activity in lachrymal gland between patients with SS1 and KCS, but there was a significant decrease in the innervation activity with regard to control subjects. All this implies that the autoimmunological factor in patients with SS1 does not significantly affect the lachrymal gland innervation.

Inervación de la glándula lagrimal en pacientes con síndrome de sjögren primario. Estudio inmunohistopatológico / Innervation of the lachrymal gland in patients with primary sjögren's syndrome. An immunohistopathological study

Objetivos: Estudiar los parámetros histopatológicos de la glándula lagrimal principal en pacientes con síndrome de Sjögren primario (SS1), comparar la relación existente entre los cambios morfológicos e inmunohistoquímicos de la inervación glandular, y analizar las diferencias inmunopatológicas entre el SS1, la queratoconjuntivitis seca (QCS) no inmunológica y personas controles. Métodos: Se estudiaron las glándulas lagrimales de pacientes con SS1, con QCS no inmunológica y de controles, mediante biopsias, usando las técnicas habituales de microscopia electrónica y el método inmunohistoquímico del polipéptido intestinal vasoactivo (VIP).Resultados: En el estroma que rodeaba a la glándula lagrimal en pacientes con SS1 se observó un número moderado de fibras nerviosas mielinizadas y no-mielinizadas. Las fibras no-mielinizadas hicieron contactos con las células glandulares, células mioepiteliales, endotelio vascular, células plasmáticas y fibroblastos. Los pacientes con QCS no inmunológica tuvieron características similares a los del SS1 en cuanto al número y actividad neuronal, mostrando un patrón morfológico prácticamente normal. Los individuos controles mostraron un número significativamente mayor de fibras nerviosas más activas. Conclusión: La glándula lagrimal principal en pacientes con SS1 estuvo claramente inervada con estructuras normales y moderadamente activas. El estudio ultraestructural demostró que no hubo diferencias significativas con la QCS no inmunológica. El estudio inmunohistoquímico mostró una actividad del VIP similar en la glándula lagrimal de los pacientes con SS1 y QCS no inmunológica, pero sí hubo una disminución significativa de la actividad nerviosa con relación a las personas controles. Ello implica que el factor autoinmune del SS1 no afecta significativamente a la inervación de la glándula lagrimal (AU)