Recent advances in age-related meibomian gland dysfunction (ARMGD).

Meibomian glands (MGs), located within the tarsal plate of the eyelid, secrete meibum which is the lipid-rich secretion necessary for stabilizing the tear film and preventing tear evaporation. Changes in the quality and quantity of meibum produced causes MG dysfunction (MGD), the leading cause of evaporative dry eye disease (EDED). MGD is an underdiagnosed disease and it is estimated that, in the US, approximately 70 % of the population over 60 have MGD. Three forms of MGD occur based on their meibum secretion: hyposecretory, obstructive, and hypersecretory MGD. The pathophysiology of MGD remains poorly understood, however aging is the primary risk factor. With age, MGs undergo various age-related changes, including decreased acinar basal cell proliferation, hyperkeratinization, MG atrophy, and eventual MG drop-out, leading to age-related MGD (ARMGD). Additionally, studies have suggested that MGs can suffer inflammatory cell infiltration and changes innervation patterns with aging, which could also contribute towards ARMGD. This review focuses on how the aging process affects the MG, and more importantly, how age-related changes to the MG can lead to MG atrophy and MG drop-out, ultimately leading to ARMGD. This review also highlights the most recent developments in potential therapeutic interventions for ARMGD.

Hemosiderotic Xanthelasmas. A New Clinicopathological Variant of Xanthelasma Palpebrarum or a Localized Variant of Xanthosiderohistiocytosis of the Eyelids?

ABSTRACT: Xanthelasma palpebrarum represent the most common subtype of cutaneous plane xanthomas. Xanthosiderohistiocytosis is considered a rare variant of xanthoma disseminatum, with only 4 cases reported to date. We report the case of a man with progressive pigmented lesions on the 4 eyelids that could correspond to hemosiderotic xanthelasmas or a localized variant of xanthosiderohistiocytosis.

Involvement of the genus Corynebacterium in the pathogenesis of pigmented intratarsal keratinous cyst.

Intratarsal keratinous cyst (IKC) is a benign cystic lesion of the eyelid that retains keratin flakes. IKCs are usually yellow to white cystic lesions but rarely become brown or gray-blue, making clinical diagnosis difficult. The mechanisms by which dark brown pigments are generated in pigmented IKC are unclear. The authors report a case of pigmented IKC that had melanin pigments within the lining of the cyst wall and within the cyst. Focal infiltrates of lymphocytes were observed in the dermis, particularly beneath the cyst wall in areas with more melanocytes and intense melanin deposition. These pigmented parts faced bacterial colonies inside the cyst, which were identified to be Corynebacterium species in a bacterial flora analysis. The pathogenesis of pigmented IKC in relation to inflammation and bacterial flora is discussed.

Relationship between actinic keratosis and malignant skin lesions on the eyelid / Relação entre ceratose actínica e lesões cutâneas malignas na pálpebra

ABSTRACT Purpose: To evaluate the variables possibly related to actinic keratosis and malignant skin lesions on the eyelid. Methods: A prospective study of patients with suspected eyelid malignancy was conducted. The participants underwent a 2-mm punch biopsy at two opposite sites of the lesion for diagnosis, and the results were compared with those of the histopathological study of the surgical excised specimen. The patients with an actinic keratosis component were divided into two groups (actinic keratosis-associated malignancy and actinic keratosis alone), which were compared for the following variables: age, disease duration, largest diameter, tumor area, Fitzpatrick classification, sex, tumor site and margin involvement. A cluster analysis was also performed. Results: We analyzed 174 lesions, of which 50 had an actinic keratosis component. Actinic keratosis was associated with squamous cell carcinoma in 22% of the cases and to basal cell carcinoma in 38%, which shows that both neoplasms may have contiguous actinic keratosis. Statistical analysis revealed no significant difference among the variables. In a cluster analysis, four groups were identified with malignant lesions in the medial canthus with the largest mean diameter and area. All margin involvements on the lower eyelid were related to malignancy, which means that all cases with margin involvement had an almost 100% risk of malignancy. Conclusions: Larger actinic keratosis lesions in the medial canthus and lesions with margin involvement on the lower eyelid have a greater probability of malignant association.

RESUMO Objetivo: Avaliar as possíveis variáveis relacionadas à ceratose actínica e lesões malignas cutâneas nas pálpebras. Métodos: Estudo prospectivo de pacientes com lesões palpebrais suspeitas de malignidade. Os participantes foram submetidos à biopsia por trépano (punch) de 2-mm em dois pontos opostos da lesão como método diagnóstico e os resultados foram comparados com o estudo histopatológico da peça excisada cirurgicamente. Aqueles que apresentaram ceratose actínica como resultado foram divididos em dois grupos (ceratose actínica associada com malignidade e ceratose actínica isolada) e foram comparados de acordo com as variáveis: idade, tempo de doença, maior diâmetro, área do tumor, classificação de Fitzpatrick, gênero, localização e acometimento da margem palpebral. A análise de cluster também foi realizada. Resultados: Foram analisadas 174 lesões e 50 delas tinham ceratose actínica como componente do tumor. Ceratose actínica esteve associada ao Carcinoma Espinocelular em 22% dos casos e ao Carcinoma Basocelular em 38%, mostrando que ambos podem ter ceratose actínica adjacente. A análise estatística não encontrou diferença entre as variáveis. A análise de cluster identificou quatro grupos e mostrou que lesões malignas no canto medial tinham maiores diâmetro e área. Acometimento da margem na pálpebra inferior relacionou-se em 100% com malignidade, enquanto a ausência de acometimento da margem mostrou menor chance de malignidade. Conclusões: Lesões maiores de ceratose actínica no canto medial e lesões com acometimento da margem palpebral inferior têm maiores chances de associação com malignidade.

Relationship between actinic keratosis and malignant skin lesions on the eyelid.

PURPOSE: To evaluate the variables possibly related to actinic keratosis and malignant skin lesions on the eyelid. METHODS: A prospective study of patients with suspected eyelid malignancy was conducted. The participants underwent a 2-mm punch biopsy at two opposite sites of the lesion for diagnosis, and the results were compared with those of the histopathological study of the surgical excised specimen. The patients with an actinic keratosis component were divided into two groups (actinic keratosis-associated malignancy and actinic keratosis alone), which were compared for the following variables: age, disease duration, largest diameter, tumor area, Fitzpatrick classification, sex, tumor site and margin involvement. A cluster analysis was also performed. RESULTS: We analyzed 174 lesions, of which 50 had an actinic keratosis component. Actinic keratosis was associated with squamous cell carcinoma in 22% of the cases and to basal cell carcinoma in 38%, which shows that both neoplasms may have contiguous actinic keratosis. Statistical analysis revealed no significant difference among the variables. In a cluster analysis, four groups were identified with malignant lesions in the medial canthus with the largest mean diameter and area. All margin involvements on the lower eyelid were related to malignancy, which means that all cases with margin involvement had an almost 100% risk of malignancy. CONCLUSIONS: Larger actinic keratosis lesions in the medial canthus and lesions with margin involvement on the lower eyelid have a greater probability of malignant association.

Ocular Mucus Membrane Pemphigoid: A Primary Versus Secondary Entity.

PURPOSE: The purpose of this review was to investigate the idea that inflammatory events of the conjunctiva and ocular surface may act as triggering events for the onset of ocular mucus membrane pemphigoid (oMMP). METHODS: A retrospective chart review of patients with biopsy-proven oMMP and no systemic pemphigoid disease. The presence, or absence, of the following inflammatory conditions at the time of OMMP diagnosis was noted: significant eyelid disease, significant atopic eye disease, Stevens-Johnson syndrome, graft-versus-host disease, viral keratitis, sarcoidosis with ocular involvement, chemical burns, medicamentosa, Sjogren syndrome, systemic lupus erythematosus with ocular involvement, and epidemic keratoconjunctivitis. Response to immunomodulatory therapy (IMT) was also recorded. RESULTS: A total of 779 patient records were identified. Conjunctival biopsy was present in 724 patients, with 646 (89.2%) being positive. One hundred thirty-nine patients (21.5%) with positive biopsies had extraocular pemphigoid disease and were excluded from further analysis. Of the 507 included patients, 154 (30.4%) had at least one of the specified inflammatory conditions present at the time of OMMP diagnosis. One hundred eighteen patients (23.3%) had only 1 such condition, 35 (6.9%) had 2, and 1 patient had 3. In patients with at least one of these conditions present, response to IMT was seen in 84.9% of patients with sufficient follow-up. CONCLUSIONS: Our study suggests that oMMP may arise as a secondary pathology to acute inflammatory events or chronic inflammatory states of the conjunctiva and ocular surface.

Safety and efficacy of a low-level radiofrequency thermal treatment in an animal model of obstructive meibomian gland dysfunction.

This study aimed to evaluate the safety and efficacy of a low-level radiofrequency thermal treatment in an obstructive MGD rabbit model. Meibomian gland orifices of the central two-thirds of the upper and lower eyelid margins were coagulated twice at 2-week intervals using a 5-MHz high-frequency electrosurgical unit. Sixteen eyes of eight rabbits were treated with one session of radiofrequency thermal treatment (radiofrequency group) and eight eyes of four rabbits were followed up without treatment (control group). Lid margin abnormality and corneal staining scores, histologic examination of the eyelids and meibombian gland, and meibography imaging were evaluated just before and 4 weeks after meibomian gland orifice closure and 4 weeks after radiofrequency thermal treatment. Lid margin abnormality score improved significantly for the upper and lower eyelids after radiofrequency thermal treatment (P < 0.001 for both eyelids). Corneal staining score remained unchanged in the radiofrequency group; however, the control group saw an increase at final follow-up. There was a significant improvement to almost baseline levels in the mean area of secretory acini in the radiofrequency group (P = 0.004). Additionally, meibography indicated an improvement in meibomian gland loss rate in the radiofrequency group. Low-level radiofrequency thermal treatment heating the inner and outer eyelid surfaces is safe and effective to treat obstructive MGD in a rabbit animal model of MGD.

Hughes flap in the management of lower lid retraction.

PURPOSE: We present a retrospective case series on the use of Hughes flap in managing acquired cicatricial lower lid retraction. METHODS: This was a multicentre, retrospective case series. Data was collected from medical records across different sites within Australia (Adelaide, Melbourne, and Sydney) and New Zealand (Hamilton). RESULTS: Fourteen patients were identified. The aetiology of cicatricial lower lid retraction included previous lid lesion excision and reconstruction, eyelid trauma, orbital fracture repair, orbital radiotherapy, and lateral canthal dystopia from previous lid surgeries. 4/14 (29%) cases had undergone other surgery to correct the retraction prior to the Hughes flap. Pre-operative lagophthalmos due to lower lid retraction was noted in 11/14 (79%) cases with a median 2 mm (range: 1-5 mm). Exposure keratopathy was present in 7/14 (50%) cases. There were no peri-operative complications during Hughes flap reconstruction. One patient had post-operative upper eyelid retraction that did not require any further intervention. One patient had persistent lagophthalmos and exposure keratopathy that is being managed conservatively. One patient had wound dehiscence and further lid retraction following flap division, which required further surgery. Median length of follow-up was 15 months (range: 0.5-84 months). At final review, improvement or resolution of symptoms was seen in 13/14 (93%) cases. CONCLUSIONS: A Hughes flap is an effective surgical technique for the management of cicatricial lower lid retraction.

Ultrapulsed CO2 ablation in the treatment of xanthelasma palpebrarum: high satisfaction treatment with low recurrence.

Xanthelasma are localized accumulation of lipid deposits on the eyelids. Lesions are typically asymptomatic and treatment is often sought for cosmetic purposes. Unfortunately, there is paucity of strong evidence in the literature for the effective treatment of normolipidaemic xanthelasmas. Lasers have been used in the management of xanthelasma and in this article the experience with ultrapulsed CO2 laser is discussed with efficacy, complications and risk of recurrence explained.

The Ocular Surface Characteristics in Prostate Cancer Patients Treated with Androgen Deprivation Therapy.

BACKGROUND: To investigate the association of long-term androgen deprivation therapy (ADT) with ocular surface characteristics in prostate cancer patients. METHODS: A total of 30 male prostate cancer patients who received ADT were selected. All candidates were scored using the Ocular Surface Disease Index (OSDI) and subsequently divided into two groups containing 9 symptomatic patients (scores >12) and 21 asymptomatic patients (scores ≤ 12). Another 20 healthy age-matched males were selected as the control group. Each candidate was assessed with respect to eyelid margin abnormality, tear film break-up time (NI-BUT), tear meniscus height (TMH), meiboscore, meibum expressibility, and demodex infection. RESULTS: The NI-BUT in the ADT group was significantly shorter than that in the control group. The scores for OSDI, eyelid margin abnormality, meibum expressibility, and meiboscores were significantly higher in the ADT group (P < 0.05). Moreover, the NI-BUT in the symptomatic ADT group was significantly shorter than that in the asymptomatic ADT group (P < 0.05). The meiboscores and meibum expressibility score in the symptomatic ADT group were significantly higher than those in the asymptomatic ADT group (P < 0.05). The presence of demodex in the symptomatic ADT group was also higher than that in the asymptomatic ADT group (P < 0.05).The length of time that patients had been taking ADT was positively correlated with meiboscores and negatively correlated with NI-BUT. CONCLUSION: Androgen levels were associated with significant changes in relative meibomian gland function. Subjective symptoms, such as dryness and foreign body sensation, were more obvious in prostate cancer patients receiving ADT, which may be caused by MGD and demodex infection. It's recommended that more attention be paid to the ocular surface in prostate cancer patients taking ADT by performing examination of NI-BUT and meibomian gland morphology and function with a view to providing more comprehensive prevention and treatment protocols.

Relationship between serum lipid level and meibomian gland dysfunction subtype in Korea using propensity score matching.

To analyze the relationship between systemic lipid profile levels and meibomian gland dysfunction (MGD) subtype in Korea. The ophthalmic data of 95 eyes and the serum lipid profiles of 95 patients were reviewed. These factors were compared with those of the general population using data from the Korean National Health and Nutrition Examination Survey (KNHANES), which evaluated 2,917 subjects. Of these, the comparison group (1:5 ratio; n = 475) was selected using propensity score matching according to age and sex. In addition, we analyzed the relationship between serum lipid profile levels and MGD subtypes in MGD patients. The mean high-density lipoprotein (HDL) value of the MGD patients was significantly higher than that of the general population (P < 0.0001). Moreover, the mean low-density lipoprotein (LDL) levels of the MGD patients was significantly lower than that of the general population (P = 0.0002). However, the mean total cholesterol (TC), and triglyceride (TG) levels of the MGD patients were not significantly different from those of the general population (TC: P = 0.4282, TG: P = 0.5613). In addition, no serum lipid levels statistically differed among the MGD subtypes (TC: P = 0.7650, HDL: P = 0.2480, LDL: P = 0.3430, TG: P = 0.7030). A statistically significant increase in HDL and decrease in LDL concentration were observed in the MGD group, although there was no difference in any serum lipid level among the MGD subtypes.

Meibography Phenotyping and Classification From Unsupervised Discriminative Feature Learning.

Purpose: The purpose of this study was to develop an unsupervised feature learning approach that automatically measures Meibomian gland (MG) atrophy severity from meibography images and discovers subtle relationships between meibography images according to visual similarity. Methods: One of the latest unsupervised learning approaches is to apply feature learning based on nonparametric instance discrimination (NPID), a convolutional neural network (CNN) backbone model trained to encode meibography images into 128-dimensional feature vectors. The network aims to learn a similarity metric across all instances (e.g. meibography images) and groups visually similar instances together. A total of 706 meibography images with corresponding meiboscores were collected and annotated for the use of network learning and performance evaluation. Results: Four hundred ninety-seven meibography images were used for network learning and tuning, whereas the remaining 209 images were used for network model evaluations. The proposed nonparametric instance discrimination approach achieved 80.9% meiboscore grading accuracy on average, outperforming the clinical team by 25.9%. Additionally, a 3D feature visualization and agglomerative hierarchical clustering algorithms were used to discover the relationship between meibography images. Conclusions: The proposed NPID approach automatically analyses MG atrophy severity from meibography images without prior image annotations, and categorizes the gland characteristics through hierarchical clustering. This method provides quantitative information on the MG atrophy severity based on the analysis of phenotypes. Translational Relevance: The study presents a Meibomian gland atrophy evaluation method for meibography images based on unsupervised learning. This method may be used to aid diagnosis and management of Meibomian gland dysfunction without prior image annotations, which require time and resources.

New Indicator of Children's Excessive Electronic Screen Use and Factors in Meibomian Gland Atrophy.

PURPOSE: To evaluate the association of children's daily electronic screen use with severe meibomian gland atrophy (MGA). DESIGN: Retrospective cross-sectional study. METHODS: Children (aged 6-17years) presenting at clinical practice December 2016 - October 2017 were evaluated for ≥grade 2 MGA vs age-matched controls with insignificant atrophy (

Severe chemosis and treatment following fronto-orbital advancement surgery for Crouzon syndrome: A case report.

RATIONALE: Crouzon syndrome is a craniofacial malformation caused by premature fusion of fibrous sutures in infants. It is one of the most common craniosynostosis syndromes, and surgery is the only effective treatment for correcting it. Postoperative complications such as encephalocele, infections, hematoma have been reported. We herein report a case of a 62-month-old boy with Crouzon syndrome who underwent fronto-orbital advancing osteotomy, cranial vault remolding, and extensive osteotomy and subsequently developed left proptosis and severe chemosis, these complications are rare and we believe it will be of use to clinicians, physicians, and researchers alike. PATIENT CONCERNS: The patient's skull had been malformed since birth, and he had been experiencing paroxysmal headaches coupled with vomiting for 4 months. Having never received prior treatment, he underwent fronto-orbital advancement at our clinic; afterward, left proptosis and severe chemosis occurred. DIAGNOSIS: The patient was diagnosed with Crouzon syndrome, and the complications included left proptosis and severe chemosis, confirmed by the clinical manifestations, physical examination, and computed tomography (CT). INTERVENTION: We carried out cranial vault remodeling and fronto-orbital advancement. We applied ophthalmic chlortetracycline ointment on the conjunctivae, elevated the patient's head, evacuated the hematoma, and carried out a left blepharorrhaphy. OUTCOMES: The proptosis and chemosis resolved with no recurrence. No other complications occurred during the follow-up period (12 months), and CT scans revealed that the hematoma had disappeared. The calvarial vault reshaping was satisfactorily performed, and the patient's vision was not impaired. LESSONS: Severe proptosis and chemosis are rare complications that can occur after fronto-orbital advancement for Crouzon syndrome. A detailed preoperative examination (including magnetic resonance imaging and CT) is essential for diagnosis. Complete hemostasis, evacuation of hematoma, and placement of a periorbital drainage tube during surgery all contribute to an effective treatment plan. An ophthalmic ointment should be administered, and the patient's head should be elevated during the procedure. Evacuation of retrobulbar epidural hematoma and blepharorrhaphy could also help relieve proptosis and chemosis. Our report describes 2 rare complications associated with the treatment for Crouzon syndrome, and we believe it will be of use to clinicians, physicians, and researchers alike.

Liquen escleroso en los párpados / Lichen Sclerosus on the Eyelids

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A rare case of a periorbital respiratory (choristomatous) cyst.

Respiratory cysts are benign lesions lined by normal respiratory epithelium. There are few reported cases localized to the orbit, while those of the eyelid are exceedingly rare. Respiratory cysts usually arise either from a non-hereditary congenital malformation, where they are distinguished as choristomatous, or from trauma. Here, we report a case of a 53-year-old man who presented with a large right lower eyelid cyst that was histopathologically diagnosed as a respiratory cyst.