Implantation of a Newly Designed Supratarsal Gold Weight versus the Traditional Pretarsal Model for the Correction of Long-standing Paralytic Lagophthalmos: A Retrospective Cohort Study.

Background The study determined to compare the clinical outcomes of traditional gold weight implantation for the correction of paralytic lagophthalmos with those of a newly designed model. Methods In this retrospective cohort study, we enrolled 30 patients (76% females; average age 60.8 ± 12 years) with facial palsy who underwent implantation of either the traditional pretarsal gold weight (PT group; n = 15) or a new supratarsal model (ST group; n = 15) from May 2014 to April 2019. The main outcome measures were the 12-month postoperative weight prominence, weight migration, improvement of lagophthalmos, upper eyelid contour, and upper eyelid ptosis. The secondary outcome was long-term (24 months) reoperative rate. Results The new model group had significantly better eyelid contour (risk ratio [RR] 3.16, 95% confidence interval [CI] 1.62-6.15, p = 0.001), less weight prominence (RR 1.74, 95% CI 1.13-2.70, p = 0.013), less weight migration (RR 1.31, 95% CI 1.12-1.54, p = 0.001), and less eyelid ptosis (RR 2.36, 95% CI 1.21-4.59, p = 0.011) than the traditional model group. Improvement of lagophthalmos was not statistically significant between the two groups (RR 1.44, 95% CI 0.72-2.91, p = 0.303). The 24-month reoperative rate was 53.3% in the PT group versus 13.3% in the ST group (RR 2.00, 95% CI 1.15-3.49, p = 0.015). Conclusion The newly designed supratarsal gold weight showed superior postoperative outcomes than the standard traditional model.

EZH2 as a major histone methyltransferase in PDGF-BB-activated orbital fibroblast in the pathogenesis of Graves' ophthalmopathy.

Graves' ophthalmopathy (GO) is an extra-thyroidal complication of Graves' disease which can lead to vision loss in severe cases. Currently, treatments of GO are not sufficiently effective, so novel therapeutic strategies are needed. As platelet-derived growth factor (PDGF)-BB induces several effector mechanisms in GO orbital fibroblasts including cytokine production and myofibroblast activation, this study aims to investigate the roles of histone lysine methyltransferases (HKMTs) in PDGF-BB-activated GO orbital fibroblasts by screening with HKMTs inhibitors library. From the total of twelve selective HKMT inhibitors in the library, EZH2, G9a and DOT1L inhibitors, DZNeP, BIX01294 and Pinometostat, respectively, prevented PDGF-BB-induced proliferation and hyaluronan production by GO orbital fibroblasts. However, only EZH2 inhibitor, DZNeP, significantly blocked pro-inflammatory cytokine production. For the HKMTs expression in GO orbital fibroblasts, PDGF-BB significantly and time-dependently induced EZH2, G9a and DOT1L mRNA expression. To confirm the role of EZH2 in PDGF-BB-induced orbital fibroblast activation, EZH2 silencing experiments revealed suppression of PDGF-BB-induced collagen type I and α-SMA expression along with decreasing histone H3 lysine 27 trimethylation (H3K27me3) level. In a more clinically relevant model than orbital fibroblast culture experiments, DZNeP treated GO orbital tissues significantly reduced pro-inflammatory cytokine production while slightly reduced ACTA2 mRNA expression. Our data is the first to demonstrate that among all HKMTs EZH2 dominantly involved in the expression of myofibroblast markers in PDGF-BB-activated orbital fibroblast from GO presumably via H3K27me3. Thus, EZH2 may represent a novel therapeutics target for GO.

Selenium supplementation in inactive moderate to severe Graves' orbitopathy patients: a randomized controlled trial.

PURPOSE: This study was designed to evaluate the effect of selenium supplementation in inactive moderate-severe Graves' orbitopathy (GO) patients. METHODS: This study was a single-center, placebo-controlled, double-masked, randomized trial. Inactive moderate-severe GO participants were randomized to receive six months of 200 micrograms/day of selenium supplementation or placebo. Thorough eye exams, clinical activity score (CAS), Graves' Ophthalmopathy quality of life questionnaire (GO-QOL), and serum selenium level were evaluated at baseline and 6 months after the interventions. The chi-squared or Fisher's exact test was used to compare categorical variables. The t-test and the paired t-test were used to compare continuous variables between two independent samples and two dependent samples, respectively. RESULTS: A total of 25 participants were enrolled, 13 in the selenium group and 12 in the placebo group. Both groups had adequate baseline serum selenium levels at 98.96 ± 15.63 mcg/L and 102.55 ± 17.71 mcg/L, respectively. After 6 months of intervention, the selenium group showed a greater improvement in palpebral aperture (mean difference: -1.4 ± 1.7 mm, p = .04) compared to the placebo group (-0.3 ± 2.7 mm). Notably, 5(41.67%) people in the placebo group developed larger palpebral apertures. Proptosis, ocular motility, and soft tissue signs did not change significantly. GO-QOL and CAS score improvement showed no statistically significant difference between both groups. Minor adverse effects were observed. CONCLUSIONS: Selenium supplementation has a positive effect on eyelid aperture even in inactive moderate-to-severe GO patients with a sufficient baseline selenium level.

Magnification of Iris through Clear Acrylic Resin in Ocular Prosthesis.

The study on the magnification of the clear acrylic resin in prosthetic dentistry is important but lacking. Hence, this research aimed to investigate the magnification of the iris in the ocular prosthesis with various thicknesses of clear heat cure acrylic resin. A total of 60 ocular prostheses were divided into six groups with various thicknesses of clear heat cure acrylic resin over the iris; T0 (control): no acrylic resin, T1: 2, T2: 4, T3: 6, T4: 8, and T5: 10 mm of clear acrylic resin over the iris. Each ocular prosthesis was manufactured from white acrylic, with a 10.250 mm iris. Then, the clear heat cure resin was placed over the iris, cured, then polished. The final diameter of the iris was measured with a vernier caliper. The sizes of the iris were compared among various groups using one-way ANOVA, and a significant level was chosen at p value = 0.01. The mean sizes of iris were T0 = 10.25, T1 = 10.92, T2 = 11.26, T3 = 11.91, T4 = 12.75, and T5 = 13.43 mm. The size of the iris was significantly different among the group (p < 0.0001). The magnification of the iris for different groups was 1.06 for T1, 1.10 for T2, 1.16 for T3, 1.24 for T4, and 1.31 for T5. The magnification of the iris increased as the thickness of clear heat cure acrylic resin over the iris is increased on the ocular prosthesis.

A Novel Patient-specific Titanium Mesh Implant Design for Reconstruction of Complex Orbital Fracture.

Complex orbital fractures, including orbital rims and walls, require precise reconstruction. A titanium-based patient-specific implant (PSI) benefits over other implants when challenged with narrow surgical space and designable implant fixation point. METHODS: This is a prospective noncomparative case series to evaluate the effect of complex orbital reconstruction using the newly designed lateral fixation patient-specific implant. The PSI was individually fabricated by 3D reconstruction using the mirrored nonaffected orbit as a template. The fixation point was at maxillary or zygomatic bone, depending on the bony remnant. Outcomes were obtained from computed tomography scan to compare orbital tissue volume and exophthalmometry value by posterior clinoid method before and after the surgery and also between both orbits in each patient. RESULTS: Sixteen patients with complex orbital fracture with inferior orbital rim defect were enrolled. Seven were previously repaired with other implants. Compared with the preoperative measurement, the postoperative mean difference of orbital volume and exophthalmometry value between both eyes was significantly decreased (reduction of the mean difference of 2904.40 mm3; P < 0.001 and 2.89 mm; P < 0.001, respectively). The mean orbital volume and exophthalmometry value between affected and unaffected eyes were not different after surgical correction (P = 0.57 and P = 0.28, respectively). There was one infected wound from retained foreign body and one unresolved vertical diplopia after the reconstruction. CONCLUSIONS: Reconstruction of complex orbital fractures using the novel designed-PSI had excellent outcomes. Appropriate implant design with caution of orbital anatomy and placement techniques are keys for successful results.

Histone Deacetylase 4 Controls Extracellular Matrix Production in Orbital Fibroblasts from Graves' Ophthalmopathy Patients.

Background: Graves' ophthalmopathy (GO) is an autoimmune eye disease with the characteristic symptoms of eyelid retraction and proptosis. Orbital fibroblast activation induced by platelet-derived growth factor-BB (PDGF-BB) stimulation plays a crucial role in GO pathogenesis, leading to excessive proliferation and extracellular matrix production by orbital fibroblasts. Currently, GO treatment options remain limited and novel therapies including targeted drugs are needed. Histone deacetylases (HDACs) are associated with the development and progression of several cancers and autoimmune diseases by epigenetically controlling gene transcription, and HDAC inhibitors (HDACis) may have therapeutic potential. Nevertheless, the role of HDACs in orbital fibroblasts from GO is unknown. Therefore, we studied the expression of HDACs as well as their contribution to extracellular matrix production in orbital fibroblasts. Methods: Orbital tissues were obtained from GO patients (n = 18) who underwent decompression surgery with approval from the Institutional Review Board of the Faculty of Medicine (Protocol number 401/61), Chulalongkorn University (Bangkok, Thailand). Furthermore, orbital tissue was obtained from control patients (n = 3) without inflammatory or thyroid disease who underwent surgery for cosmetic reasons. Orbital fibroblast cultures were established from the orbital tissues. HDAC mRNA and protein expression in orbital fibroblasts was analyzed by reverse transcription-quantitative real-time PCR and Western blot. PDGF-BB-activated orbital fibroblast and orbital tissues were treated with HDACis or HDAC4 small-interfering RNA. Results: PDGF-BB-stimulated orbital fibroblasts had upregulated HDAC4 mRNA and protein expression. HDAC4 mRNA expression was significantly higher in GO compared with healthy control orbital fibroblasts. Histone H3 lysine 9 acetylation (H3K9ac) decreased upon PDGF-BB stimulation. Treatment with HDAC4i (tasquinimod) and HDAC4/5i (LMK-235) significantly decreased both proliferation and hyaluronan production in PDGF-BB-stimulated orbital fibroblasts. HDAC4 silencing reduced mRNA expression of hyaluronan synthase 2 (HAS2), collagen type I alpha 1 chain (COL1A1), Ki67, and α-smooth muscle actin (α-SMA), as well as hyaluronan production in PDGF-BB-stimulated orbital fibroblasts. Tasquinimod significantly reduced HAS2 and α-SMA mRNA expression in whole orbital tissue. Conclusion: Our data indicated, for the first time, that altered HDAC4 regulation along with H3K9 hypoacetylation might represent a mechanism that contributes to excessive proliferation and extracellular matrix production by orbital fibroblasts in GO. HDAC4 might represent a novel target for GO therapy.

Contralateral Mueller's muscle-conjunctiva resection: a therapeutic option in thyroid eye disease patients with unilateral eyelid retraction.

Purpose: To evaluate pre- and post-operative marginal reflex distance 1 (MRD1) when conducting Mueller's muscle-conjunctiva resection (MMCR) on the normal eyelid of thyroid eye disease (TED) patients with unilateral eyelid retraction.Methods: This was a retrospective non-comparative case series. Medical records of TED patients with unilateral eyelid retraction, who underwent a contralateral MMCR from November 2015 to September 2017, were reviewed. Standard photographs of pre-operative, post-phenylephrine test and post-operative were measured for eyelid positions including MRD1, MRD2 and inter-palpebral fissure width. MMCR was indicated on the contralateral eyelid only in patients who had a cosmetically acceptable result from phenylephrine test and were willing to receive the operation on the normal eye.Results: Twelve TED patients who underwent MMCR on the normal eyelid were included in the study. Mean pre-operative MRD1 of retracted and normal eyelid were 5.7 mm (SD = 0.86) and 3.5 mm (SD = 0.65), respectively. Mean post-operative MRD1 of retracted and normal eyelid were 4.4 mm (SD = 0.76) and 4.1 mm (SD = 0.46), respectively. The asymmetry of MRD1 between eyes was significantly decreased from 2.1 mm (inter-quartile range (IQR) = 1.5-2.9 mm) pre-operatively to 0.3 mm (IQR = 0.1-0.7 mm) post-operatively (p = .002). None of these patients needed further eyelid correction surgery and there was no complication.Conclusions: In TED patients with unilateral eyelid retraction, using phenylephrine test on their normal eyes should be initiated. If eyelid position was satisfactorily equalized, performing MMCR on the normal eyelid is considered an effective alternative treatment with a predictable outcome.

Development and psychometric properties of the Thai Graves' ophthalmopathy quality of life (GO-QOL) questionnaire.

PURPOSE: To develop and assess the psychometric properties of the Thai version of the Graves' Ophthalmopathy Quality of Life (GO-QOL) questionnaire. BACKGROUND: Graves' ophthalmopathy (GO) is a chronic condition that causes negative self-image and impaired visual function. These conditions impact quality of life (QOL) but are rarely documented. Graves' Ophthalmopathy Quality of Life Questionnaire (GO-QOL) has good validity, reliability and responsiveness. In this study we developed a Thai GO-QOL questionnaire by translating the questionnaire from English to the Thai language and evaluated its reliability and validity. PATIENTS AND METHODS: Forward and backward translations were performed independently by four translators with extensive experience in both English and Thai. Seventy patients at the thyroid clinic responded to the Thai translated version upon their first visit and again 2-3 weeks afterwards. Validity was assessed by the content validity index (CVI) and correlation with relevant clinical parameters. Reliability was evaluated by Cronbach's alpha, the intraclass correlation coefficient, and the Bland-Altman plot. RESULTS: The Thai GO-QOL version showed high CVI (0.97) and a moderate negative correlation of the functional QOL score with disease severity (r = - 0.49), the clinical activity score (r = - 0.31), and exposure parameter (r = - 0.32). It showed good reliability with a high intraclass correlation coefficient (0.92) and high Cronbach' s coefficient (0.86). CONCLUSION: The Thai GO-QOL has good validity and reliability. It can be used to evaluate the quality of life of Graves' ophthalmopathy patients as a consequence of their disease in thyroid treatment programs.

Corrigendum: Differences Between Single and Double Eyelid Anatomy in Asians Using Ultrasound Biomicroscopy.

This corrects the article DOI: 10.1097/APO.0000000000000185.

External Levator Advancement versus Müller Muscle-Conjunctival Resection for Aponeurotic Blepharoptosis: A Randomized Clinical Trial.

BACKGROUND: The purpose of this study was to compare the efficacy of external levator advancement and Müller muscle-conjunctival resection in aponeurotic blepharoptosis repair. METHODS: Mild to moderate blepharoptosis patients with good levator function and a positive phenylephrine test were randomized to upper blepharoplasty with either external levator advancement or Müller muscle-conjunctival resection. The primary outcome was marginal reflex distance 1 at 1 month after surgery. Secondary outcomes were cosmetic outcome, complications, and operating room time. RESULTS: Forty patients were enrolled, six men and 34 women, with an average age of 62.4 years. The mean preoperative marginal reflex distance 1 in the levator group (39 eyes/20 subjects) and the Müller group (38 eyes/20 subjects) was 1.2 ± 0.8 mm and 1.5 ± 0.7 mm, respectively. The mean postoperative marginal reflex distance 1 in the levator and Müller groups was 3.0 ± 1.0 mm and 3.2 ± 1.0 mm, respectively. The difference in the mean change was 0.008, and was not statistically different (95 percent CI, -0.59 to 0.61; p = 0.978). The mean cosmetic outcome was 2.69 ± 0.81 for the levator group and 3.07 ± 0.68 for the Müller group, with a mean difference of 0.373 (95 percent CI, 0.06 to 0.69; p = 0.020). The average operating room time was 75 ± 19.2 minutes for the levator group and 71 ± 23.6 minutes for the Müller group (p = 0.439). There were four eyes that underwent reoperation, three in the levator group (7.7 percent) and one in the Müller group (2.6 percent). CONCLUSIONS: External elevator advancement and Müller muscle-conjunctival resection are both effective in correction of mild to moderate blepharoptosis. However, Müller muscle-conjunctival resection yields a statistically significant better cosmetic outcome and causes less eyelid asymmetry. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Cytokeratin-Negative Undifferentiated (Lymphoepithelial) Carcinoma of the Lacrimal Sac.

Epstein-Barr virus-associated undifferentiated (lymphoepithelial) carcinoma is a malignancy that most commonly arises in the nasopharynx but can also occur in other locations including the lacrimal sac. Generally, this tumor strongly expresses cytokeratin, making the diagnosis straightforward. In the absence of confirmatory immunohistochemistry, the diagnosis can be problematic, particularly for tumors arising in unusual locations. Only 3 cases arising in the lacrimal sac in association with Epstein-Barr virus have been reported in the English literature, and all showed typical pathologic findings. The authors report a fourth case, unique in that it showed negative immunostaining for all cytokeratins tested. The clue to the nature of the tumor came from identification of Epstein-Barr virus by in-situ hybridization and demonstration of tonofilaments by electron microscopy. This case demonstrates that a multimodal approach may be needed in the diagnosis of Epstein-Barr virus-associated carcinoma, especially when occurring in uncommon locations.

The new focus on epicanthoplasty for Asian eyelids.

PURPOSE OF REVIEW: Purpose of review is to emphasize the clinical significance of the epicanthal fold when evaluating Asian eyelids. Advances in Asian eyelid research have improved the understanding of the epicanthal fold and highlighted key steps to performing successful epicanthoplasty. Up-to-date epicanthoplasty surgical techniques are also discussed. RECENT FINDINGS: The epicanthal fold is common in the Asian population. It is composed of the preseptal part of the orbicularis oculi muscle. Various epicanthoplasty techniques have been described and can be broadly categorized into two types based on the type of skin flap created: the advancement flap and the transposition flap. The skin flap can be created in several ways depending on surgeon preference and the severity of the epicanthal fold but is not the key step in epicanthoplasty. Releasing all vertical tension by subcutaneous tissue dissection and orbicularis oculi myectomy are the main surgical steps to successful correction. Earlier described epicanthoplasty methods created obvious scarring, under correction, and recurrent deformity. Newer techniques offer improvements with a shorter skin incision, smaller flap creation, and minimal or no medial canthal ligament plication to lessen wound tension. SUMMARY: For optimal surgical results in Asian upper eyelid surgery, presence of the epicanthal fold and surgical correction options should be discussed primarily.

Differences Between Single and Double Eyelid Anatomy in Asians Using Ultrasound Biomicroscopy.

PURPOSE: The aim of this study was to clarify the differences between single and double eyelid structures quantitatively using an ultrasound biomicroscopy. DESIGN: A single-center observational study. METHODS: Upper eyelids of Asian volunteers were evaluated with a 50-MHz ultrasound biomicroscopy. The skin-orbicularis oculi complex (SOOC), levator aponeurosis, Mueller muscle-conjunctival complex, and tarsus were imaged at the eyelid crease in the double eyelid group and 7 mm above the eyelid margin in the single eyelid group. The SOOC was also measured 2 mm above the eyelid margin and 5 mm above the eyelid crease. RESULTS: Forty-two upper eyelids of 42 subjects were studied. Mean SOOC thickness at the eyelid crease was 0.62 ± 0.12 mm in single eyelids and 0.57 ± 0.08 mm in double eyelids (P = 0.03). Mean SOOC thickness at 2 mm above the eyelid margin and 5 mm above the crease was not significantly different between single and double eyelids (P = 0.004 and P = 0.62, respectively). The levator aponeurosis, Mueller muscle-conjunctival complex, and tarsus measured 0.38 ± 0.12 mm, 0.86 ± 0.28 mm, and 10.84 ± 1.10 mm in single eyelids and 0.39 ± 0.14 mm, 0.88 ± 0.34 mm, and 10.61 ± 1.36 mm in double eyelids (P = 0.75, P = 0.81, and P = 0.54, respectively). CONCLUSIONS: Single eyelids showed slightly thicker SOOC in the pre-tarsal area and at the eyelid crease but not 5 mm above the eyelid crease. The levator aponeurosis, Mueller muscle-conjunctival complex, and tarsus showed no differences in thickness.

Update on Asian eyelid anatomy and clinical relevance.

PURPOSE OF REVIEW: Asians make up the world's largest ethnic group, and the eyelid is one of the most prominent features of the face, regardless of race. Recent advances in Asian eyelid research have improved the understanding of its unique anatomy and, more importantly, highlighted differences surgeons should be aware of when performing Asian eyelid surgery. RECENT FINDINGS: The most obvious characteristic of the Asian eyelid is the absent or very low lid crease and fuller upper eyelid. Caucasian eyelids typically have a double eyelid, but Asian eyelids can be categorized into three types: single eyelid, low eyelid crease, and double eyelid. Morphological variations in each layer from the different skin complexities to a taller, more circular-shaped orbital bone create a different eyelid appearance. Some components such as a submuscularis fibroadipose tissue layer and a lower-positioned transverse ligament were recently identified and found exclusively in the Asian eye. Many eyelid crease formation theories have been postulated, but none is scientifically proven because multiple factors are possibly involved. SUMMARY: Thorough understanding of Asian eyelid anatomy is imperative. The eyelid is the key distinctive feature of the Asian eye. Improving patient appearance while maintaining ethnic characteristics is the goal of Asian eyelid surgery.

Case report of orbital cellulitis and necrotizing fasciitis from melioidosis.

A 48-year-old Thai male farmer presented with progressive swelling of the right eyelid and high-grade fever. His visual acuity declined and the right side of his forehead developed a necrotic skin lesion with a purulent discharge. CT of the orbits suggested orbital cellulitis with subperiosteal abscess. Intravenous ceftriaxone and clindamycin were given empirically but then switched to vancomycin and meropenem because of rapid deterioration together with clinical sepsis. Burkholderia pseudomallei was isolated from the blood 3 days after the treatment, and the antibiotics were then switched to intravenous ceftazidime. The liver enzymes were elevated, and imaging of the abdomen revealed liver and splenic abscesses. After 14 days, the patient showed marked clinical improvement, became afebrile, and regained his OD visual acuity. A repeat CT of the orbit showed improvement with no subperiosteal abscess. The antibiotic was then switched to oral trimethoprim/sulfamethoxazole in combination with doxycycline for 6 months.