Thyroid eye disease: Redefining its management-A review.

Thyroid eye disease (TED) is a debilitating, vision threatening disease that dramatically alters patients' quality of life. Until recently, the management of TED is a long arduous course with supportive therapy, followed by an extensive surgical treatment plan to reverse the disease endpoints. Teprotumumab offers an early, safe therapeutic intervention to help reverse disease end points such as diplopia and proptosis and improve quality of life.

Warfarin-associated delayed orbital hemorrhage after orbital fracture repair with smooth nylon foil implant.

The authors describe the first report in the literature of delayed orbital hemorrhage that may be partly caused by supratherapeutic anticoagulation. A 52-year-old man with supratherapeutic international normalized ratio (INR) presented with acute proptosis, orbital pain and diplopia 9 months after the floor and medial orbital wall fracture repair using nylon foil implant. He was found to have hemorrhaged into the capsule surrounding the orbital implant. Three weeks later, the patient underwent implant removal after warfarin was discontinued for 5 days and INR was normalized. His symptoms resolved postoperatively. This case describes a unique risk factor of delayed orbital hemorrhage in patients with previous orbital fracture repair, and highlights that coagulopathy should be investigated in patients presenting with acute proptosis with a history of orbital fracture repair. The authors also provide a comprehensive and up-to-date literature review on previously reported cases with delayed hemorrhagic complications from alloplastic orbital implants.

Comparison of clinical outcomes of conjunctivo-mullerectomy for varying degrees of ptosis.

To compare the success of conjunctivo-mullerectomy in patients with varying degrees of ptosis and identify factors affecting outcomes and complications. The prospective cohort was studied in patients with ptosis undergoing conjunctivo-mullerectomy with or without tarsectomy were enrolled. Ptosis was classified as mild, moderate, and severe per margin-to-reflex distance 1 (MRD1). Postoperative MRD1, complications, and 3-month success rates were evaluated. The study enrolled 258 ptotic eyes of 159 patients. Most eyes (233; 90.3%) achieved surgical success, 14 (5.4%) were overcorrected, and 11 (4.3%) were undercorrected. The success rates for mild, moderate, and severe ptosis were 96.6%, 91.7%, and 83.5%, respectively. The mild and moderate ptosis groups had a nonsignificant difference in success (- 4.9%; 95% CI - 12.0% to 4.5%; P = 0.36). However, the mild and severe ptosis groups' rates significantly differed (- 13.1%; 95% CI - 23.6% to - 1.9%; P = 0.03). For all 3 ptosis groups, the success rates of individuals undergoing surgery without tarsectomy did not significantly differ. Patients undergoing conjunctivo-mullerectomy with tarsectomy had an increased risk of unsuccessful surgery (OR 3.103; 95% CI 1.205-7.986; P = 0.019). In conclusions, Conjunctivo-mullerectomy is safe and effective for all ptosis severities. The success rate was significantly lower for severe ptosis than mild or moderate ptosis. Levator muscle function was not associated with unsuccessful outcomes, but tarsectomy was.

Predictors for Recurrence of Cytomegalovirus Retinitis in HIV-Negative Patients.

PURPOSE: To investigate the incidence of and predictive factors for recurrent cytomegalovirus retinitis (CMVR) in human immunodeficiency virus (HIV)-negative patients. METHODS: A retrospective review of HIV-negative patients who were newly diagnosed with CMVR between January 2005 and February 2019. RESULTS: Of 28 patients (44 eyes), 35.9% of eyes had a recurrence of CMVR after discontinuation of anti-CMV therapy. The incidence of CMVR recurrence was 17 per 100 eye-years. The factors significantly associated with CMVR recurrence were eyes with retinitis area of more than 25% (P = .013), absence of vitreous haze (P = .003), neutropenia at presentation (P = .001), and absence of systemic immunosuppression therapy prior to presentation (P = .002). CONCLUSION: Eyes with a large area of retinitis, absence of vitreous haze, and neutropenia at presentation are predictive of CMVR recurrence while receiving systemic immunosuppression prior to CMVR presentation has a lower risk of CMVR recurrence.

Simplified technique for lateral canthal tendon canthopexy.

Purpose: Different techniques for lateral canthal suspension have been used in the management of various eyelid malpositions. We describe a simplified technique for lateral canthal suspension and review its outcome along with a review of existing variations. Methods: We conducted a retrospective chart review of 28 eyelids in 22 patients who underwent simplified lateral canthal suspension. Demographics, symptoms at presentation, and associated eyelid malposition were noted. We evaluated the palpebral fissure and margin-reflex distance 2 (MRD2) on the preoperative and final postoperative photographs by using MEEI FACE-gram software. We also reviewed existing literature on different surgical management options for comparison. Results: At three-month postoperative follow-up, presenting symptoms resolved in all cases. The average postoperative decease in palpebral fissure was 0.73 mm (P = 0.018) and the average decrease of the MRD2 was 1.02 mm (P = 0.0003). Recurrence occurred by three months in one eyelid (4%) with ectropion due to moderate eyelid laxity, and this case was managed with tarsal strip procedure. One patient (5%) who had bilateral surgery had asymmetric lower eyelid position and one patient (5%) had persistent edema of the operated eyelid for six months. Conclusion: This simplified canthal suspension is a simple and effective technique that tightens the lateral canthal tendon and improves the lower eyelid position. It can be used in various mild-to-moderate eyelid laxities and has favorable operative characteristics compared with many existing techniques.

Germline ATM mutation and somatic PIK3CA and BCOR mutations found in an infant with aggressive orbital embryonal rhabdomyosarcoma.

PURPOSE: To report a case of aggressive infantile orbital embryonal rhabdomyosarcoma harboring germline ATM mutation and 2 somatic mutations as revealed by next-generation sequencing and the potential application for personalized therapy. OBSERVATIONS: A 7-month-old male developed a rapidly progressive left proptosis over 6 weeks due to a large medial orbital mass. Biopsy revealed embryonal rhabdomyosarcoma. After the first cycle of chemotherapy, re-imaging showed interval tumor enlargement with intracranial extension. Craniotomy, combined with orbital exenteration, was performed. Tumor specimens and blood samples were sent for 596 gene DNA sequencing panels with RNA-sequencing focused on actionable mutations as well as gene fusion detection. Sequencing revealed 3 clinically relevant mutations: a germline ATM loss-of-function (LOF) mutation, a somatic PIK3CA gain-of-function mutation, and a somatic BCOR LOF mutation. No chromosomal translocation was detected. Workup for metastasis was positive for bone marrow involvement. Despite standard high-dose adjuvant chemotherapy in combination with radiation therapy, the patient died 10 months later with metastatic diseases. CONCLUSIONS AND IMPORTANCE: This case highlights an aggressive form of embryonal rhabdomyosarcoma in an infantile orbit. The presence of germline mutation may explain the increased chemo-resistance and adverse prognosis, and may be used as the target for genomic-directed therapy.

Successful Ocular Surface Reconstruction in Complete Ankyloblepharon With the Simple Oral Mucosal Epithelial Transplantation Technique: A Case Report.

PURPOSE: To report an outcome of a patient with complete ankyloblepharon successfully managed with simple oral mucosal epithelial transplantation (SOMET). METHODS: A 55-year-old woman presented with complete adhesion of both lids to the ocular surface as a complication from Stevens-Johnson syndrome. We performed 2-staged reconstructive surgeries: the first stage was to perform ankyloblepharon lysis and surface reconstruction with a mucosal graft on the palpebral area and an amniotic membrane on the bulbar area, and the second stage was to reconstruct the bulbar area with a transplantation of small pieces of oral mucosa (SOMET technique). Postoperatively, the patient was evaluated for ocular surface stability, recurrent symblepharon, in vivo confocal microscopy, and impression cytology with immunofluorescence staining. RESULTS: Complete epithelialization of cornea-like epithelium was observed within 6 weeks after SOMET was performed. The ocular surface was stable over 1 year. Both fornices remained deep. In vivo confocal microscopy showed cornea-like epithelium mixed with conjunctival epithelium, as confirmed with immunofluorescence staining, which revealed cytokeratin 3, cytokeratin 7, and cytokeratin 12 positivity. CONCLUSIONS: SOMET is a simple modified technique using minimal oral mucosal tissue to regenerate epithelialization for complicated ocular surface reconstruction such as a complete ankyloblepharon repair. Although there was evidence of conjunctival invasion, stable ocular surface and deep fornices can be achieved for further visual rehabilitative procedure.

Partial protection of Simian immunodeficiency virus (SIV)-infected rhesus monkeys against superinfection with a heterologous SIV isolate.

Although there is increasing evidence that individuals already infected with human immunodeficiency virus type 1 (HIV-1) can be infected with a heterologous strain of the virus, the extent of protection against superinfection conferred by the first infection and the biologic consequences of superinfection are not well understood. We explored these questions in the simian immunodeficiency virus (SIV)/rhesus monkey model of HIV-1/AIDS. We infected cohorts of rhesus monkeys with either SIVmac251 or SIVsmE660 and then exposed animals to the reciprocal virus through intrarectal inoculations. Employing a quantitative real-time PCR assay, we determined the replication kinetics of the two strains of virus for 20 weeks. We found that primary infection with a replication-competent virus did not protect against acquisition of infection by a heterologous virus but did confer relative control of the superinfecting virus. In animals that became superinfected, there was a reduction in peak replication and rapid control of the second virus. The relative susceptibility to superinfection was not correlated with CD4(+) T-cell count, CD4(+) memory T-cell subsets, cytokine production by virus-specific CD8(+) or CD4(+) cells, or neutralizing antibodies at the time of exposure to the second virus. Although there were transient increases in viral loads of the primary virus and a modest decline in CD4(+) T-cell counts after superinfection, there was no evidence of disease acceleration. These findings indicate that an immunodeficiency virus infection confers partial protection against a second immunodeficiency virus infection, but this protection may be mediated by mechanisms other than classical adaptive immune responses.

Orbital Infection by Saksenaea vasiformis in an Immunocompetent Host.

Orbital mucormycosis caused by Saksenaea vasiformis is extremely rare. Herein, we report an immunocompetent 22-year-old Thai female who presented with two months of progressive right upper eyelid mass, associated with swelling, redness, and ptosis. She failed to improve despite multiple courses of antibiotic and steroid treatment. Computed tomography (CT) scan showed infiltration involving the upper eyelid and lacrimal gland. Fungal hyphae were revealed by histopathological study. Polymerase chain reaction (PCR) was positive for Saksenaea vasiformis (GenBank: accession number FR687327.1). The patient was successfully treated with surgical debridement, amphotericin B, and oral posaconazole.

TWO CASES OF ACUTE RETINAL NECROSIS DUE TO VARICELLA ZOSTER DESPITE PRIOR SHINGLES VACCINATION.

PURPOSE: To review two cases of acute retinal necrosis in adults due to varicella zoster virus despite prior shingles vaccination. METHODS: Retrospective chart review. PATIENTS: A 62-year-old man and a 64-year-old man with unilateral acute retinal necrosis who had shingles vaccinations 16 and 7 months before their ocular symptoms. RESULTS: Polymerase chain reaction confirmation of varicella zoster virus in the anterior chambers of both patients. Both patients had good responses to oral antiviral therapy and topical and/or oral steroids. DISCUSSION: These two cases demonstrate that singles vaccination is not an absolute protection against varicella zoster virus-related acute retinal necrosis. However, such vaccination may reduce the severity of the acute retinal necrosis.

Traumatic Endophthalmitis due to Cellulosimicrobium cellulans.

Purpose. To report a case of traumatic endophthalmitis due to Cellulosimicrobium cellulans. Design. Case report. Methods. Retrospective chart review. Results. To our knowledge, this is the first report of traumatic endophthalmitis due to C. cellulans, which did not respond to intravitreal antibiotics or repeat vitrectomy and ultimately led to the discovery of an occult intraocular foreign body. Conclusions. C. cellulans is a rare cause of endophthalmitis. Greater awareness of this bacterium in the ophthalmic literature as a cause of endophthalmitis and its association with foreign bodies may allow earlier and more purposeful intervention in future cases.

Primary congenital glaucoma associated with Patau syndrome with long survival.

Ocular abnormalities are common in Patau syndrome (trisomy 13), but only a few cases with congenital glaucoma have been reported, some of which were associated with other ocular defects. This report describes a case of primary congenital glaucoma in an 11-year-old patient with full trisomy 13.

Multiplex cytokine analysis reveals elevated concentration of interleukin-8 in glaucomatous aqueous humor.

PURPOSE: To test the hypothesis that immune activation occurs in glaucoma by comparing concentrations of multiple cytokines in aqueous humor (AH) from patients with primary open angle glaucoma (POAG) and from cataract patients without glaucoma as controls. METHODS: Cytokine concentrations in AH obtained during surgery were measured using microparticle-based immunoassays. Localized expression of IL-8 protein was investigated by immunohistochemistry of human eyes. RESULTS: Eight cytokines (IL-1ß, IL-2, IL-4, IL-5, IL-10, IL-12, IFN-γ, and TNF-α) were below the limits of detection, and two cytokines (IL-18 and IL-15) were detected at low levels or in only a few patients. Although IL-6 was detected in 26 of 30 control patients (median, 2.7 pg/mL) and in 23 of 29 POAG patients (median, 1.6 pg/mL), the difference was not statistically significant. IL-8 was detected in 28 of 30 control patients (median, 1.8 pg/mL) and in all 29 POAG patients (median, 4.9 pg/mL). The higher IL-8 concentration in the AH of POAG patients was statistically significant (P < 0.001). In pairs of eyes from patients with asymmetric glaucomatous optic nerve damage, IL-8 concentration was higher in the AH of the more severely affected eye (P < 0.05). Patients with severe visual field defects had higher IL-8 concentrations in the AH than did patients with mild visual field defects. IL-8 protein expression was found in human retina and optic nerve. CONCLUSIONS: Concentration of the inflammatory cytokine IL-8 is significantly elevated in the AH of POAG patients, supporting the hypothesis that immune activation occurs in glaucoma.

Compensatory substitutions restore normal core assembly in simian immunodeficiency virus isolates with Gag epitope cytotoxic T-lymphocyte escape mutations.

The evolution of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) as they replicate in infected individuals reflects a balance between the pressure on the virus to mutate away from recognition by dominant epitope-specific cytotoxic T lymphocytes (CTL) and the structural constraints on the virus' ability to mutate. To gain a further understanding of the strategies employed by these viruses to maintain replication competency in the face of the intense selection pressure exerted by CTL, we have examined the replication fitness and morphological ramifications of a dominant epitope mutation and associated flanking amino acid substitutions on the capsid protein (CA) of SIV/simian-human immunodeficiency virus (SHIV). We show that a residue 2 mutation in the immunodominant p11C, C-M epitope (T47I) of SIV/SHIV not only decreased CA protein expression and viral replication, but it also blocked CA assembly in vitro and virion core condensation in vivo. However, these defects were restored by the introduction of upstream I26V and/or downstream I71V substitutions in CA. These findings demonstrate how flanking compensatory amino acid substitutions can facilitate viral escape from a dominant epitope-specific CTL response through the effects of these associated mutations on the structural integrity of SIV/SHIV.