A novel classification of senile dermatochalasis: insights from clinical and histological analysis.

PURPOSE: Dermatochalasis is a common disorder of the elderly, often requiring upper blepharoplasty. Although it is mainly accepted as a process of aging, its clinical and histological findings vary among patients. The aim of this study was to classify types of dermatochalasis based on their clinical and histological findings. METHODS: This retrospective study included patients with dermatochalasis who had undergone senile blepharoplasty at a single center. Clinical parameters such as margin-to-reflex distance 1 (MRD1), eyelid contour, visual field, and pre-existing medical conditions were assessed. Histological analysis was conducted of eyelid tissues stained with hematoxylin and eosin (H&E) and D2-40 to evaluate dermal edema, inflammation, lymphatic changes, and stromal depth. RESULTS: This study included 67 eyes of 35 patients. The mean age of the patients was 69.0 ± 8.3 years, and the average MRD1 was 1.8 ± 1.3 mm. In correlation analysis, two distinct types of dermatochalasis based on the histological findings were identified: lymphangiectasia-dominant and stromal edema-dominant types. The difference between nasal and temporal side MRD1(NT-MRD1) showed the area under the ROC curve of 0.718 of for distinguishing the two histological types of dermatochalasis was 0.718. CONCLUSION: Our novel classification of senile dermatochalasis based on morphological and histological analysis provides insights into the underlying pathology and may help to predict surgical outcomes and complications.

Eye and lid involvement as an uncommon feature of pemphigus foliaceus in a pediatric patient.

Pemphigus foliaceus (PF) is an autoimmune blistering disorder which affects the superficial layers of the epidermis with rare mucosal involvement. We present the case of a 12-year-old girl with PF involving the eyes and eyelids. A literature review of pediatric nonendemic PF revealed another two cases with ocular manifestations. Eyelid involvement is an uncommon feature of PF that should be properly identified and treated.

Relationship between histopathological findings of patients with dermatochalasis and vitamin D deficiency.

PURPOSE: To compare the histopathological findings of patients who had been diagnosed with dermatochalasis (DC) and had undergone upper eyelid blepharoplasty (ULB) as well as those of controls (C-Group) according to their serum vitamin D (SVD) levels. METHODS: The prospective study included 136 upper eyelid skin from 68 patients who underwent surgery for DC and 53 upper eyelid skin from 53 patients who underwent levator surgery with ULB. The DC Group was then divided into 3 subgroups according to the marginal reflex distance (MRD4). The lymphatic vessel (LV) count and diameter of the largest LV (DLLV) were recorded, the stromal collagen bed (SCB) was observed, and its depth was measured, the interfibrillar edema was examined, and the elastic fiber and macrophage counts and recorded, respectively, and then all of these were evaluated. The SVD levels were compared between the DC patients and the C-Group. RESULTS: In comparison to the C-Group, significant changes were seen in the dilated LV, DLLV, SCB depth, interfibrillar edema, elastic fiber density, and macrophage count in the DC sub-Groups (P < 0.001 for all). While no difference was found between DC sub-Group 1 (MRD4 > 4 mm) and the C-Group (P > 0.05), a significant difference was found between DC sub-Group 2 (MRD4 2-4 mm) and DC sub-Group 3 (MRD4 < 2 mm) for all of the parameters (P < 0.05). A statistically significant difference was also found in the SVD levels between the DC sub-Group 1 and DC sub-Groups 2-3 (P < 0.017, P < 0.001 respectively). CONCLUSION: According to the results of this study, SVD level was significantly lower in DC group. Moreover, an increased LV count and diameter, decreased elastic fiber count, collagen fiber and stromal edema irregularity, and increased macrophage count were found to be associated with the SVD level.

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.

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.

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.

Unique Variant of Cerebrotendinous Xanthomatosis Presenting With Eyelid Involvement Due to Heterozygous CYP7A1 and SLC10A1 Gene Mutations.

ABSTRACT: We report a case of a novel phenotypic variant of cerebrotendinous xanthomatosis (CTX) with an adult onset, caused by 2 coexisting mutations involving the CYP7A1 and SLC10A1 genes. A 49-year-old male patient presented with eyelid xanthomatosis associated with dermatochalasis, nystagmus, right-sided paresis with hyperreflexia and atypical parkinsonism. Bilateral xanthomatous plaques involving both Achilles tendons were subsequently detected. Histopathology of the eyelids demonstrated marked diffuse stromal infiltrates of prominent foamy histiocytes. His lipid profile showed only a slightly elevated non-high density lipoprotein cholesterol level but with normal cholesterol and cholestanol levels. By contrast, classic CTX characteristically demonstrates a markedly elevated cholestanol and a mutation involving the CYP27A1 gene for enzyme cholesterol 27-hydroxylase. Unexpectedly, molecular studies on this patient revealed a heterozygous mutation involving 2 different genes, namely, CYP7A1 and SLC10A1 genes. The CYP7A1 gene encodes for the enzyme cholesterol 7α-hydroxylase, which is a rate-limiting enzyme in the cholesterol degradation. The SLC10A1 Na+/taurocholate cotransporter gene is involved in the enterohepatic circulation of bile acids and for the hepatocyte uptake of cholesterol. We are the first to report an unusual case of an adult-onset CTX manifesting with eyelid xanthomas associated with an uncharacteristic lipid profile and a detection of novel heterozygous mutations of CYP7A1 and SLC10A1 genes in this neurocutaneous syndrome.

Phakomatous Choristoma of the Eyelid and Orbit: A Case Report.

Phakomatous choristoma was first described as a distinct pathologic entity by Zimmerman in 1971. Report of only 26 cases of this tumor so far is an indicator of the rarity of phakomatous choristoma. We present a 4-month-old infant with an orbital mass beneath the right lower eyelid. Surgical excision was undertaken and the histopathologic findings of a dense fibrocollagenous stroma containing small to medium size islands and glandular-like structures surrounded by thick basement membrane and filled by amorphous eosinophilic material confirmed the diagnosis. Immunohistochemical study showed positive staining for S-100 and vimentin and negative staining for cytokeratins, glial fibrillary acidic protein, smooth muscle actin, synaptophysin, CD34, melan-A, and epithelial membrane antigen markers. This is the first patient with phakomatous choristoma presented from our country and the 27th reported case worldwide. Phakomatous choristoma is a rare, benign congenital tumor of lenticular anlage, almost always presenting in the medial lower eyelid and anterior orbit. Surgical excision is curative and allows precise diagnosis due to the unique histopathologic and immunostaining characteristics of this choristoma.

Unilateral Periocular Intralymphatic Histiocytosis, Associated With Rosacea (Morbihan Disease).

Intralymphatic histiocytosis is a rare reactive skin condition characterized by a nonspecific clinical presentation and, microscopically, by the collections of mononuclear histiocytes within the lumina of dilated lymphatic vessels. We report a rare case of intralymphatic histiocytosis associated with rosacea and prominent periocular edema (Morbihan disease). The patient is a 56-year-old woman with a 12-year history of rosacea who suddenly developed edema of the right upper eyelid that persisted 6 months before she sought medical advice. Because of an unclear clinical diagnosis, surgical excision of the edematous upper eyelid was performed. The histologic slides showed interstitial edema of the dermis with dilated vascular channels and small epithelioid cell granulomas around hair follicles. In addition, there were aggregates of cells inside numerous lymphatic vessels that were immunohistochemically positive for CD45, CD4, CD68, CD163, CD64, CD14, CD11c, and lysozyme and negative for CD3, CD20, CD30, CD56, S100, CD1a, and langerin.

Bilateral third eyelid ectopic cilia in an adult horse.

A 15-year-old Cob mare presented with a 4-month history of chronic epiphora and intermittent blepharospasm in the right eye. On ophthalmic examination, two translucent aberrant hairs were identified at the third eyelid margin corresponding to an area of corneal fibrosis and neovascularization. Partial excision of the third eyelid was performed, and histopathology confirmed ectopic hair follicles. Two weeks later, clinical signs recurred in the same eye. Examination revealed another pair of aberrant hairs on the bulbar surface of the third eyelid near its leading edge. This portion of the third eyelid was also excised, and histopathology confirmed two additional ectopic hair follicles. Eight months later, the horse developed similar clinical signs in the left eye. Ophthalmic examination showed a single aberrant translucent hair at the third eyelid margin associated with focal fibrosis and neovascularization of the ventromedial cornea. Partial excision of the third eyelid was performed, and histopathology confirmed an ectopic hair follicle within the third eyelid conjunctiva. Excision was curative at 4 years postoperatively with no further recurrence in either eye.

Intravascular papillary endothelial hyperplasia of the periocular region.

Intravascular papillary endothelial hyperplasia (IPEH) is a benign vascular lesion, typically found in the skin, consisting of a papillary proliferation of endothelial cells intimately related to a thrombus; it appears to be a rare variant of an organizing process. IPEH very rarely develops in the periocular region, with fewer than 20 such cases currently reported in the English language literature. We describe one of the largest ever case series of this uncommon lesion occurring in the periocular region and discuss its clinical features, imaging characteristics, and surgical management.

Value of ultrasound biomicroscopy in assessment of small masses at medial canthal region.

PURPOSE: Conventional imaging techniques are not sensitive enough to reveal detailed structures of lacrimal drainage system (LDS) and its surrounding tissue (ST). Our study aimed to explore utility of ultrasound biomicroscopy (UBM) in assessment of small masses at the medial canthal region and compare performance of UBM with conventional imaging techniques. METHODS: We prospectively recruited cases with small mass (long axis < 1 cm) at the medial canthal region (upper LDS-located area) from June 2017 to October 2018. UBM ± color Doppler flow imaging (CDFI) and conventional imaging techniques (computed tomography, magnetic resonance imaging, and dacryocystography) were conducted by four independent practitioners. Results were analyzed against gold standards with Cohen's kappa test in three aspects including LDS patency, mass location, and presumptive diagnosis. Corresponding gold standards were syringe and dacryocystography, intraoperative findings, and pathological/empirical diagnosis. RESULTS: Seventy-two cases were recruited, including 20 cases of LDS lesions and 52 cases of ST lesions. Female (odds ratio 7.14) and age ≥ 37 (odds ratio 9.80) were risk factors for LDS lesion, and age range of 15-25 (odds ratio 9.17) was a risk factor for inflammatory ST lesion. In terms of LDS patency, UBM results were reliable for the detection of pre-saccal obstruction (kappa = 0.920), but were not reliable for intra-saccal and post-saccal obstruction (kappa = 0.106). In terms of mass location, the UBM (kappa = 0.766) performed better than conventional techniques (except for dacryocystography) to sort out ST lesions, with sensitivity of 93.8% and specificity of 83.3%. In terms of diagnosis, the UBM (kappa = 0.882) outweighed conventional techniques (except for magnetic resonance imaging) to distinguish cysts from nodules, with sensitivity of 93.8% and specificity of 94.4%. Notably, the UBM + CDFI achieved better performance than the UBM when screen out inflammatory lesions (kappa = 0.926 vs kappa = 0.689) and LDS-adjacent lesions (kappa = 0.815 vs kappa = 0.673), resulting in sensitivity of 91.7% and specificity of 100% for both testing items. If deep lesions (at the lacrimal sac-harbored area) were excluded, UBM reliability to detect inflammatory lesions (kappa = 0.915) and LDS-adjacent lesions (kappa = 0.770) improved, achieving sensitivity of 90.0% and 88.9%, and specificity of 100.0% and 92.7%, respectively. CONCLUSIONS: The UBM is a valuable tool to assess superficial masses at the medial canthal region regarding pre-saccal obstruction, mass location, and presumptive diagnosis. TRIAL REGISTRATION: This work was registered on Chinese Clinical Trial Registry website with registration number ChiCTR1800018956 .

Epibulbar complex choristoma with simultaneous involvement of eyelid: a case report.

BACKGROUND: Epibulbar complex choristoma, a rare congenital epibulbar tumor, has many diverse forms. Reviewing the literature, it can present clinically as either a circumferential or isolated epibulbar mass, limbal tumor, lateral canthal mass, aggregate of ectopic cilia in the upper eyelid, eyelid mass mimicking chalazion, or lacrimal caruncle mass. The management depends on the extent of involvement, the risk of amblyopia, and cosmetic concerns. Here, we report an atypical presentation of epibulbar complex choristoma with simultaneous eyelid involvement. CASE PRESENTATION: A 1-month-old full-term boy was brought to our clinic with congenital epibulbar mass of the right eye with simultaneous eyelid involvement. Dilated fundus examination was unremarkable. Survey for linear nevus sebaceous Jadassohn was negative. Due to concerns of possible amblyopia and cosmetics, lamellar keratectomy, sclerotomy, and conjunctivoplasty were performed to remove the epibulbar lesion. The eyelid defect was reconstructed with 6-0 Vicryl sutures. Histopathological examination reported complex choristoma. Upon three-year follow-up, low astigmatism and favorable cosmetics results were achieved. CONCLUSIONS: Congenital complex choristoma can present clinically as an epibulbar mass with eyelid involvement. The management depends on the extent of involvement, the risk of amblyopia, and cosmetic concerns. The method of eyelid reconstruction should be tailored according to the residual eyelid defect.

Endometriosis of the Eyelid, an Extraordinary Extra-abdominal Location Highlighting the Spectrum of Disease.

Cutaneous endometriosis is an uncommon dermatologic disorder predominantly seen in young women. Most commonly, it presents within a region of a previous surgical scar, often in relation to a gynecologic procedure on the abdomen or in close proximity to the umbilicus. The typical clinical presentation is that of papules or nodules with monthly cyclical pain and size variation. Histologically, the lesions are composed of endometrial stroma and glands. The pathophysiology is not well understood but is believed to be due to metastasis or seeding of endometrial cells. When this uncommon disorder occurs outside of the most typical clinical setting, it may cause some diagnostic difficulty. In this report, we present the first known case of cutaneous endometriosis on the eyelid.

Histopathological Study on the Proposed Pathogenesis of Intratarsal Keratinous Cysts.

PURPOSE: Intratarsal keratinous cysts (IKCs) are a recently described entity that is frequently misdiagnosed clinically as chalazia and mislabeled in the literature as "intratarsal epidermal inclusion cysts" or "epidermoid cysts." It is important to accurately diagnose IKCs and distinguish them from chalazia because IKCs require a complete surgical excision and can exhibit multiple recurrences following curettage. The authors performed a retrospective case series to further elucidate the pathogenesis of IKCs and to determine the diagnostically optimal panel of stains for diagnosis. METHODS: A study group of 8 specimens of IKCs and control specimens of epidermal inclusion cysts were obtained from their pathology laboratories. The authors compared the histological and immunohistochemical profile of IKCs and epidermal inclusion cysts by staining sections from each specimen with hematoxylin and eosin, periodic acid-Schiff, Masson trichrome, cytokeratin 5, cytokeratin 17, carcinoembryonic antigen, and epithelial membrane antigen. The immunoreactivity data were then analyzed using a 2-tailed Mann-Whitney test, assuming a nonparametric population (p < 0.05 is significant). RESULTS: Histopathologically, IKCs are embedded in the tarsus lined by stratified squamous epithelium with an inner undulating cuticle filled with a compact keratinous-appearing material. The authors demonstrate that IKCs develop progressively from dilated meibomian ducts to the formation of complete cysts with their markers. The most valuable immunochemical stains to diagnose IKC were cytokeratin 17, carcinoembryonic antigen, and epithelial membrane antigen (p < 0.05 with each). CONCLUSIONS: These findings provide a better understanding of the pathogenesis and the immunohistochemical findings of this relatively new entity allowing for more appropriate diagnosis of IKCs aiming to reduce future complications from their management.

Granulomatous Inflammation of the Upper Eyelid After Autologous Fat Injection.

A 45-year-old female came to the clinic complaining of periorbital swelling and ptosis on the left upper eyelid that had started 6 months previously. She had received an autologous fat injection in the forehead 6 months prior, and there was no other ophthalmologic history. There were no abnormal findings, including pupil, extraocular movement, or fundus examination. There was eyebrow elevation of the left upper eyelid, and the marginal reflex distance 1 was 1 mm on the left eye compared to 4 mm on the right eye. There were a 2-cm-sized round and firm mass on the left upper eyelid that was not accompanied by tenderness. Orbital computed tomography showed heterogeneous infiltration with an ill-defined margin. Excisional biopsy and levator advancement were performed on the left upper eyelid, and histological findings showed chronic granulomatous inflammation with foreign body reaction and fat necrosis.A complete history for patient presentation with autologous fat injection is important when a periorbital mass is encountered clinically because granulomatous inflammation of the eyelid may occur after autologous fat injection in the forehead and can be related to migration of the injected fat.

An unusual case of idiopathic calcinosis of the eyelid.

Idiopathic subepidermal calcinosis, also known as idiopathic calcinosis cutis, is a rare condition, which typically presents as a small, hard, subepithelial mass in the absence of systemic disease and trauma. We report on an atypical case of idiopathic calcinosis, which appeared in an otherwise healthy 61-year-old female along the tarsus of her right upper eyelid. The purpose of this case report is to demonstrate idiopathic calcinosis in an unusual location that is deep to the dermis and to discuss the vast differential diagnosis of this entity.

Ectodysplasin A protein promotes corneal epithelial cell proliferation.

The EDA gene encodes ectodysplasin A (Eda), which if mutated causes X-linked hypohidrotic ectodermal dysplasia (XLHED) disease in humans. Ocular surface changes occur in XLHED patients whereas its underlying mechanism remains elusive. In this study, we found Eda was highly expressed in meibomian glands, and it was detected in human tears but not serum. Corneal epithelial integrity was defective and the thickness was reduced in the early postnatal stage of Eda mutant Tabby mice. Corneal epithelial cell proliferation decreased and the epithelial wound healing was delayed in Tabby mice, whereas it was restored by exogenous Eda. Eda exposure promoted mouse corneal epithelial wound healing during organ culture, whereas scratch wound assay showed that it did not affect human corneal epithelial cell line migration. Epidermal growth factor receptor (EGFR), phosphorylated EGFR (p-EGFR), and phosphorylated ERK1/2 (p-ERK) were down-regulated in Tabby mice corneal epithelium. Eda treatment up-regulated the expression of Ki67, EGFR, p-EGFR, and p-ERK in human corneal epithelial cells in a dose-dependent manner. In conclusion, Eda protein can be secreted from meibomian glands and promotes corneal epithelial cell proliferation through regulation of the EGFR signaling pathway. Eda release into the tears plays an essential role in the maintenance of corneal epithelial homeostasis.