Correlation between extraocular muscle enlargement and thyroid autoantibodies in thyroid eye disease.

PURPOSE: This study aimed to investigate the factors affecting extraocular muscle enlargement in thyroid eye disease (TED). STUDY DESIGN: Retrospective study. METHODS: The thyroid-stimulating hormone (TSH) receptor antibody (TRAb), thyroid-stimulating antibody (TSAb), antithyroid peroxidase antibody (ATPO), and antithyroglobulin antibody (ATG) levels in patients diagnosed with TED who underwent orbital magnetic resonance imaging were assessed. The control group comprised the contralateral eye of patients who underwent orbital magnetic resonance imaging (MRI) for unilateral eyelid tumors or orbital disease. The thickness of the bilateral rectus muscles and superior oblique muscles was measured on orbital MRI. Muscle enlargement was classified as unilateral/bilateral and symmetric/asymmetric. The effects of age, sex, smoking history, TSH, thyroid hormone, and thyroid autoantibodies on the muscle thickness and number of enlarged muscles were assessed by use of simple and multiple regression analyses. RESULTS: The TED and control groups comprised 41 and 44 cases, respectively. The positivity rate of TSAb in patients with TED was 92.7% higher than that of the other autoantibodies. Muscle enlargement was observed in 29 of the 41 cases (70.7%). Older age and higher TSAb levels were identified as significant factors affecting the total muscle thickness and number of enlarged muscles. Bilateral muscle enlargement and asymmetrical muscle enlargement were observed in 17 (58.6%) and 23 (79.3%) of the 29 cases, respectively. The TSAb levels and age had no significant effect on the type of muscle enlargement. CONCLUSIONS: TSAb showed significant associations with extraocular muscle enlargement. Measurement of TSAb, rather than of TRAb, may be more useful for diagnosing extraocular muscle enlargement in patients with TED.

Correlation of Ocular Biometry with Axial Length in Elderly Japanese.

Purpose: Ocular parameters are not only useful for diagnosing diseases but also for guiding treatment approaches. A lot of previous studies have reported ocular parameters and its relations before cataract surgery. However, despite ethnic differences in ocular biometry, few reports have dealt with Japanese. Hence, this retrospective cross-sectional study aimed to measure parameters of preoperative cataract patients and examines the correlations between each parameter in Japanese elderly people. Patients and Methods: The 210 subjects had their ocular axial lengths measured with OA-2000. The endpoints were ocular axial length (AL), central corneal thickness (CCT), average anterior corneal radius of curvature (CR), white-to-white (WTW), anterior chamber depth (ACD), and lens thickness (LT). Our analyses utilized the eye with the longer AL in each person. Each parameter was analyzed for correlations in a round-robin manner. Regression analyses were performed on parameters correlated with AL. Results: The parameters correlated with AL were CR (r = 0.33, P < 0.0001), WTW (r = 0.29, P < 0.0001), ACD (r = 0.59, P < 0.0001), and LT (r = -0.30, P < 0.0001). These parameters related to AL in all simple regression equations (CR (P < 0.0001), WTW (P = 0.0002), ACD (P < 0.0001), LT (P = 0.0001)). In multiple regression analyses, CR, ACD, and LT might relate to AL (CR (P = 0.0002), ACD (P < 0.0001), LT (P = 0.018)). LT tended to be thinner as AL increased, while CR, WTW, and ACD tended to increase. Conclusion: This information may be useful in developing strategies for ophthalmic surgery, as it provides information on the location of intraocular tissues. Various parameters have been used in intraocular lens (IOL) power calculations in recent years and knowledge of the interrelationship among parameters may be useful in determining IOL power according to ethnicity in the future.

Adenoid cystic carcinoma of the orbit without lacrimal gland involvement and with intracranial extension: A case report.

We present a 76-year-old female with a 6-year history of decreased vision in the right eye and right-sided facial neuralgia. She had a T1 isointense and T2 isointense enhancing lesion in the right orbit and the middle cranial fossa on MRI examination. Granulomatous disease or meningioma was suspected, however, after removal, the tumor was identified by pathology as adenoid cystic carcinoma (ACC). The tumor has no radiological and clinical lacrimal grand involvement. ACC shows a slow and indolent growth pattern but is associated with poor long-term outcomes, mainly due to perineural invasion, local control failure, and distant metastasis. This case highlights the importance of a pathologic diagnosis and early intervention in similar presentations.

Clinicopathological features of epiretinal membranes in eyes filled with silicone oil.

PURPOSE: The aim of this case series was to clarify the clinicopathological features of epiretinal membranes (ERMs) that developed in eyes after silicone oil (SO) tamponade to treat rhegmatog-enous retinal detachments (RRDs). PATIENTS AND METHODS: In the Department of Ophthalmology, Saitama Medical Center, Jichi Medical University, patients with idiopathic ERMs (23 eyes) and ERMs in eyes filled with SO (SO ERMs) after vitreous surgery to treat RRDs (nine eyes) were enrolled from July 2012 to March 2014. ERM tissues obtained intraoperatively were examined histopathologically. Besides the main outcome measure of the pathological findings of the ERM tissues, other outcome measures included the preoperative findings on optical coherence tomography (OCT) images and the surgical findings. RESULTS: Eight (89%) of nine eyes with SO ERMs had bilayered membranes composed of a firm layer on the retinal side with glial cells and extracellular matrix and a fragile sponge-like layer on the vitreous side. The sponge-like layer was composed of emulsified SO surrounded by macrophages. Quantitative analysis showed that the areas with cluster of differentiation 68 (CD68)-positive macrophages identified by immunohistochemistry in eyes with SO ERMs were significantly (P<0.001) larger than those in eyes with idiopathic ERMs. The findings on OCT images were consistent with the pathological features of the SO ERMs. Surgical removal of the SO ERMs was difficult because the sponge-like layer was fragile, and the underlying retina was also fragile due to inflammation. CONCLUSION: SO ERMs are bilayered membranes. Long-standing emulsified SO formed a sponge-like layer and SO (foreign body)-induced granulation and caused retinal inflammation in these eyes, making surgical removal difficult. A preoperative OCT examination is necessary to identify SO ERMs.

Caruncular and Pericaruncular Sebaceous Gland Hyperplasia: A Report of 2 Cases and Literature Review.

PURPOSE: To report the clinical and histopathological features of two patients with caruncular and pericaruncular sebaceous gland hyperplasia (SGH) with a literature review. METHODS: We performed a retrospective pathology database search of 1195 ophthalmic specimens receiving the clinical diagnosis of SGH for caruncular/pericaruncular lesions during 2004 to 2014 at Tokyo Dental College, Ichikawa General Hospital. Paraffin sections were stained with hematoxylin and eosin. A retrospective patient record and literature review was also performed. RESULTS: Database search disclosed 2 male patients with SGH of 1195 specimens (0.15%). Pathological specimens revealed neither any cellular/nuclear atypia nor any mitotic figures and invasive features. No recurrences were observed in these 2 cases 12 to 18 months after excision. CONCLUSIONS: Caruncle and pericaruncular SGH is an uncommon lesion which needs careful histopathological evaluation for differentiation especially from caruncular neoplasias.

[Bilateral Endogenous Fungal Subretinal Abscesses due to Scedosporium prolificans: a Case Report].

BACKGROUND: We report a case with bilateral endogenous fungal subretinal abscesses. To our knowledge, this is the first report from Japan in which Scedosporium prolificans (S. prolificans) was cultured from intraocular tissue. CASE: A 74-year-old man, receiving chemotherapy for acute myeloid leukemia, complained of visual loss in both eyes. Best-corrected visual acuity was hand motion in the right and 2/200 in the left eye. His right eye showed exophthalmos, inflammation in the anterior chamber and iris neovascularization. Funduscopy revealed no details as there was vitreous opacity in the right eye, and irregular round yellowish-white subretinal lesions involving the macula in the left eye. Blood culture was negative, and C-reactive protein (CRP) and ß-D glucan titers were high. An antifungal drug and broad-spectrum antibiotics were initiated. Two days after the initial visit, right visual acuity had deteriorated to light perception. Enucleation of the right eye was performed for diagnosis and treatment. Fungi were cultured from the subretinal lesion, confirming a diagnosis of S. prolificans infection. After systemic administration and intravitreal injections of antifungal agents, the subretinal abscess in the left eye gradually diminished. At present, six months after the first visit, left visual acuity is 20/200. CONCLUSION: Although S. prolificans endophthalmitis can be intractable, this case suggests that repeated intravitreal antifungal agent injections can be effective.

Correlations between choroidal abnormalities, Lisch nodules, and age in patients with neurofibromatosis type 1.

To evaluate correlations between choroidal abnormalities, Lisch nodules, and age in patients with neurofibromatosis type 1 (NF1), we examined ten cases with NF1 using near-infrared reflectance imaging. Patients ranged in age from 4 to 39 years. The angle used for near-infrared reflectance imaging was 55°. We counted the total number of choroidal abnormalities in an area within a 55° angle centered on the fovea and the total number of Lisch nodules on the iris by slit-lamp examination. No positive correlation was found between the number of Lisch nodules and patient age (Spearman's rank correlation coefficient ρ=0.117, P=0.7414). Choroidal abnormalities tended to increase with age (ρ=0.6150), but this difference was not statistically significant (P=0.0650). A positive correlation was found between the number of choroidal abnormalities and Lisch nodules (ρ=0.783, P=0.0267). In conclusion, choroidal abnormalities tend to increase with patient age and are correlated with the number of Lisch nodules.

Classification of secondary corneal amyloidosis and involvement of lactoferrin.

PURPOSE: To classify secondary corneal amyloidosis (SCA) by its clinical appearance, to analyze the demographics of the patients, and to determine the involvement of lactoferrin. DESIGN: Retrospective, observational, noncomparative, multicenter study. PARTICIPANTS: Twenty-nine eyes of 29 patients diagnosed with SCA by corneal specialists at 9 ophthalmologic institutions in Japan were studied. METHODS: The clinical appearance of SCA was determined by slit-lamp biomicroscopy and was classified into 3 types. The demographics of the patients, for example, age, gender, and the duration of the basic disease (trichiasis, keratoconus, and unknown), were determined for each clinical type. Surgically excised tissues were stained with Congo red and antilactoferrin antibody. The postoperative prognosis also was determined. MAIN OUTCOME MEASURES: Clinical appearance of the 3 types of SCA, along with the gender, age, and duration of the basic diseases were determined. RESULTS: Classification of SCA into 3 types based on clinical appearance found 21 cases with gelatinous drop-like dystrophy (GDLD)-like appearance (GDLD type), 3 cases with lattice corneal dystrophy (LCD)-like appearance (LCD type), and 5 cases with the combined type. Patients with the GDLD type were younger (average age: 40.9 years for the GDLD type, 74.3 years for the LCD type, and 46.8 years for the combined type), predominantly women (85.7% for the GDLD type, 33.3% for the LCD type, and 60% for the combined type), and had the basic disease over a longer time (average duration: 22.1 years for the GDLD type, 14.0 for the LCD type, and 11.4 for the combined type). The distribution of the basic diseases (trichiasis vs. keratoconus vs. unknown) was not significantly different for each type. Surgical treatments, for example, phototherapeutic keratectomy, lamellar keratoplasty, and simple keratectomy, resulted in a good resolution in all surgically treated cases. One subject dropped out of the study. Spontaneous resolution was seen in one subject after epilation of the cilia. Amorphous materials in the excised tissues showed positive staining results by Congo red and by antilactoferrin antibody. CONCLUSIONS: Secondary corneal amyloidosis can be classified into 3 clinical types based on its clinical appearance. Larger numbers of females and lactoferrin expression were seen in all 3 types. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Accumulation of secretory vesicles in the lacrimal gland epithelia is related to non-Sjögren's type dry eye in visual display terminal users.

Previous observations in a rat model of a non-Sjögren's syndrome (non-SS) type of dry eye seen in users of visual display terminals (VDT) indicated that secretory vesicle (SV) accumulation in the lacrimal gland epithelia contributes to the condition. Here, to examine this possibility in humans, we compared the lacrimal gland histology and percent SV area in the cytoplasm of acinar epithelial cells using light microscopy and transmission electron microscopy, in patients with VDT work-related non-SS dry-eye (VDT group), SS-induced dry-eye, and autopsied normal controls. In addition, the VAMP8 (vesicle-associated membrane protein 8, an exocrine-pathway molecule) and Rab3D (mature vesicle marker) were histochemically examined in lacrimal gland tissue sections. The lacrimal gland acini were larger in the VDT group than in the SS group, and the percent SV area was significantly higher in the VDT group than in the normal controls (P = 0.021) or SS group (P = 0.004). Immunostaining revealed abnormal distributions of VAMP8 in the VDT and SS groups. Rab3D was more strongly expressed in the cytoplasm of acinar epithelial cells in the VDT group than in that of normal controls. The duration of VDT use was significantly longer in the VDT group than in the other groups. These findings suggest that excessive SV accumulation in the acinar epithelia may contribute to the reduced tear secretion in VDT users.

Perturbation of transforming growth factor (TGF)-beta1 association with latent TGF-beta binding protein yields inflammation and tumors.

Transforming growth factor-beta (TGF-beta) activity is controlled at many levels including the conversion of the latent secreted form to its active state. TGF-beta is often released as part of an inactive tripartite complex consisting of TGF-beta, the TGF-beta propeptide, and a molecule of latent TGF-beta binding protein (LTBP). The interaction of TGF-beta and its cleaved propeptide renders the growth factor latent, and the liberation of TGF-beta from this state is crucial for signaling. To examine the contribution of LTBP to TGF-beta function, we generated mice in which the cysteines that link the propeptide to LTBP were mutated to serines, thereby blocking covalent association. Tgfb1(C33S/C33S) mice had multiorgan inflammation, lack of skin Langerhans cells (LC), and a shortened lifespan, consistent with decreased TGF-beta1 levels. However, the inflammatory response and decreased lifespan were not as severe as observed with Tgfb1(-/-) animals. Tgfb1(C33S/C33S) mice exhibited decreased levels of active TGF-beta1, decreased TGF-beta signaling, and tumors of the stomach, rectum, and anus. These data suggest that the association of LTBP with the latent TGF-beta complex is important for proper TGF-beta1 function and that Tgfb1(C33S/C33S) mice are hypomorphs for active TGF-beta1. Moreover, although mechanisms exist to activate latent TGF-beta1 in the absence of LTBP, these mechanisms are not as efficient as those that use the latent complex containing LTBP.

A technique for preventing spontaneous loss of lacrimal punctal plugs.

PURPOSE: To describe a technique for the prevention of spontaneous loss of lacrimal punctal plugs. DESIGN: Interventional case series. METHODS: Four consecutive patients (10 puncta in seven eyes) with severe dry eyes who experienced repeated spontaneous plug loss underwent punctal occlusion by suturing plugs with 10-0 polypropylene sutures. RESULTS: All punctal plugs were fitted to lacrimal puncta by anchoring the sutures. Plug retention rate was 80% at 6 months after the procedure. CONCLUSION: Suturing punctal plugs is effective in the production of long-term punctal closure in patients with repeated spontaneous plug loss.

Subconjunctival mucosa-associated lymphoid tissue (MALT) lymphoma arising in Tenon's capsule.

PURPOSE: We report the first case of subconjunctival mucosa-associated lymphoid tissue (MALT) lymphoma arising in Tenon's capsule (fascia bulbi). METHODS: A 75-year-old woman presented with painless swelling of the superior bulbar conjunctiva in her left eye. During the biopsy of the bulbar lymphoid lesion, it was noticed that the conjunctiva was movable and that the lesion was located in the subconjunctiva. The tissues were studied by conventional light microscopy, immunohistochemistry, flow cytometry, and gene rearrangement analysis. RESULTS: Histopathological examination revealed that a diffuse lymphoid infiltrate consisting of small-sized lymphoid cells was present in Tenon's capsule but not in the substantia propria of the conjunctiva. Immunohistochemical and flow cytometric studies documented tumor cells of B-lymphocyte lineage. Molecular analysis demonstrated positive immunoglobulin heavy chain gene rearrangement. The final diagnosis was subconjunctival MALT lymphoma arising in Tenon's capsule. CONCLUSION: Ophthalmologists and pathologists need to distinguish the subconjunctival lymphoma that arises in Tenon's capsule from the conjunctival lymphoma in the substantia propria during diagnosis of epibulbar lymphoid tumors.

[Incidence of benign and malignant lesions of eyelid and conjunctival tumors].

PURPOSE: To examine the incidence of benign and malignant eyelid lesions and conjunctival tumors. SUBJECTS AND METHODS: One-hundred-and twenty-eight cases (131 eyes) which were treated during the period from January 1990 to February 2004 were histopathologically diagnosed for eyelid or conjunctival tumors (87 cases of eyelid tumors and 41 cases of conjunctival tumors) in retrospective evaluations. The incidence of benign or malignant lesions, the pathological classification, age, sex, and clinical diagnostic accuracy were all investigated. RESULTS: Sixty-four (73%) of the tumors were found to be benign eyelid tumors. The common benign eyelid tumors were 14 nevocellular nevi, 9 seborrheic keratosis, 7 epidermoid cysts, and 6 papillomas. Twenty-four (27%) eyelid tumors were malignant. These included 9 basal cell carcinomas, 9 sebaceous gland carcinomas, 4 malignant lymphomas, and 2 metastatic tumors. Thirty-four (79%) conjunctival tumors were benign, and the common benign conjunctival tumors were 9 nevocellular nevi and 7 papillomas. Nine (21%) conjunctival tumors were malignant, comprising 7 malignant lymphomas and 2 squamous cell carcinomas. The mean ages of malignant eyelid and conjunctival tumor patients were significantly older than those of benign tumor patients. Clinical accuracy in predicting basal cell carcinoma and sebaceous gland carcinoma was 11.1% and 44.4%, respectively. CONCLUSIONS: Approximately 70 approximately 80% of all eyelid and conjunctival tumors are benign. Clinicians should suspect that the lesions are malignant when seeing elderly patients with eyelid or conjunctival tumors. Excised eyelid lesions should be submitted for histopathologic confirmation because there are some cases where clinical diagnosis does not match pathological diagnosis.

Expression of truncated latent TGF-beta-binding protein modulates TGF-beta signaling.

Transforming growth factor-beta is released from most cells as an inactive complex consisting of transforming growth factor-beta, the transforming growth factor-beta propeptide and the latent transforming growth factor-beta-binding protein. We studied the role of latent transforming growth factor-beta-binding protein in modulating transforming growth factor-beta availability by generating transgenic mice that express a truncated form of latent transforming growth factor-beta-binding protein-1 that binds to transforming growth factor-beta but is missing the known N- and C-terminal matrix-binding sequences. As transforming growth factor-beta is an inhibitor of keratinocyte proliferation and is involved in the control of hair cycling, we over-expressed the mutated form of latent transforming growth factor-beta-binding protein under the control of the keratin 14-promoter. Transgenic animals displayed a hair phenotype due to a reduction in keratinocyte proliferation, an abbreviated growth phase and an early initiation of the involution (catagen) phase of the hair cycle. This phenotype appears to result from excess active transforming growth factor-beta, as enhanced numbers of pSmad2/3-positive nuclei are observed in transgenic animal skin. These data suggest that the truncated form of latent transforming growth factor-beta-binding protein-1 competes with wild-type latent transforming growth factor-beta-binding protein for binding to latent transforming growth factor-beta, resulting in latent transforming growth factor-beta complexes that fail to be targeted correctly in the extracellular matrix. The mis-localization of the transforming growth factor-beta results in inappropriate activation and premature initiation of catagen, thereby illustrating the significance of latent transforming growth factor-beta-binding protein interaction with transforming growth factor-beta in the targeting and activation of latent transforming growth factor-beta in addition to previously reported effects on small latent complex secretion.

Molecular cloning of the mouse Ltbp-1 gene reveals tissue specific expression of alternatively spliced forms.

Latent transforming growth factor binding proteins (Ltbp-1, -2, -3 and -4) and fibrillins (Fbn-1 and -2) are structurally related cysteine-rich extracellular matrix proteins that localize to the 10 nm microfibrils. Ltbp-1 is thought to promote the secretion and proper folding of the small latent transforming growth factor beta (TGF-beta) complex (TGF-beta plus its propeptide) and is implicated in sequestering it in the extracellular matrix. Here we report the isolation of the mouse Ltbp-1 complementary DNA (cDNA) and gene. The longer form of the Ltbp-1 cDNA encodes a predicted 1713 amino acid protein containing 18 epidermal growth factor-like repeats, four 8-cysteine domains and several motifs that suggest interactions with alpha(IV)beta(1) and alpha(9)beta(1) integrins. Northern blotting analyses indicate that long and short Ltbp-1 transcripts are widely expressed in adult mouse tissues and most abundantly expressed in heart. Ltbp-1 is a single copy gene that maps to chromosome 17, band E (1-3) and encompasses more than 212 kb. The Ltbp-1 gene contains 34 exons and shows a similar organization to the LTBP-2 gene, suggesting that these genes originated from a common ancestral gene.

Anatomy and histopathology of human meibomian gland.

PURPOSE: To investigate histopathologic changes in human meibomian gland. METHODS: Human meibomian gland samples were obtained at autopsy from 50 men and 33 women aged from 17 to 87 years with a mean age (+/- SD) of 61 +/- 13 years. Pieces of tarsal plate measuring 3 x 3 mm including meibomian glands were excised from the center of both upper eyelids, then fixed and embedded in paraffin. Sections 4-microm thick were stained with hematoxylin and eosin and periodic acid-Schiff. Light microscopy was used to observe any histopathologic changes. RESULTS: The following histopathologic changes were observed: (1) cystic dilatation of acini and/or ducts, (2) atrophy of acini, (3) basement membrane thickening of acini, (4) granulation tissue, and (5) lipogranulomatous inflammation. CONCLUSION: Various histopathologic changes were observed in the human meibomian gland. Hyperkeratinization of ductal epithelium and atrophy of acinar cells may cause meibomian gland dysfunction.