Incidental Diagnosis of Four Lid Orbital Lymphoma during a Blepharoplasty.

Chronic lymphocytic leukemia is characterized by the accumulation of mature CD5-positive B-cells in the lymphoid organs.1 Extranodal involvement occurs in up to 10% of cases and can arise in various tissues, including the orbit. Less than 400 cases of orbital lymphoma are diagnosed per year in the United States, typically manifesting as a form of B-cell non-Hodgkin lymphoma, with extranodal marginal zone B-cell lymphoma being the most common subtype. Orbital lymphoma typically presents with proptosis and a palpable mass; however, patients may also have a relatively benign examination. Here, we present a 76-year-old man with symmetric dermatochalasis and marked fat prolapse of all four lids, who was incidentally diagnosed with secondary orbital lymphoma in all four eyelids during a cosmetic four lid blepharoplasty. His history was significant for RAI Stage 0 chronic lymphocytic leukemia diagnosed 15 years before consultation. Orbital lymphoma presenting as orbital fat prolapse has only been reported a few times in the literature. To our knowledge, this is the first case of secondary orbital lymphoma in all four eyelids found incidentally during an aesthetic four lid blepharoplasty.

Salmonella Typhimurium expressing chromosomally integrated Schistosoma mansoni Cathepsin B protects against schistosomiasis in mice.

Schistosomiasis threatens hundreds of millions of people worldwide. The larval stage of Schistosoma mansoni migrates through the lung and adult worms reside adjacent to the colonic mucosa. Several candidate vaccines are in preclinical development, but none is designed to elicit both systemic and mucosal responses. We have repurposed an attenuated Salmonella enterica Typhimurium strain (YS1646) to express Cathepsin B (CatB), a digestive enzyme important for the juvenile and adult stages of the S. mansoni life cycle. Previous studies have demonstrated the prophylactic and therapeutic efficacy of our plasmid-based vaccine. Here, we have generated chromosomally integrated (CI) YS1646 strains that express CatB to produce a viable candidate vaccine for eventual human use (stability, no antibiotic resistance). 6-8-week-old C57BL/6 mice were vaccinated in a multimodal oral (PO) and intramuscular (IM) regimen, and then sacrificed 3 weeks later. The PO + IM group had significantly higher anti-CatB IgG titers with greater avidity and mounted significant intestinal anti-CatB IgA responses compared to PBS control mice (all P < 0.0001). Multimodal vaccination generated balanced TH1/TH2 humoral and cellular immune responses. Production of IFNγ by both CD4+ and CD8+ T cells was confirmed by flow cytometry (P < 0.0001 & P < 0.01). Multimodal vaccination reduced worm burden by 80.4%, hepatic egg counts by 75.2%, and intestinal egg burden by 78.4% (all P < 0.0001). A stable and safe vaccine that has both prophylactic and therapeutic activity would be ideal for use in conjunction with praziquantel mass treatment campaigns.

A low dose adenovirus vectored vaccine expressing Schistosoma mansoni Cathepsin B protects from intestinal schistosomiasis in mice.

BACKGROUND: Schistosomiasis is an underestimated neglected tropical disease which affects over 236.6 million people worldwide. According to the CDC, the impact of this disease is second to only malaria as the most devastating parasitic infection. Affected individuals manifest chronic pathology due to egg granuloma formation, destroying the liver over time. The only FDA approved drug, praziquantel, does not protect individuals from reinfection, highlighting the need for a prophylactic vaccine. Schistosoma mansoni Cathepsin B (SmCB) is a parasitic gut peptidase necessary for helminth growth and maturation and confers protection as a vaccine target for intestinal schistosomiasis. METHODS: An SmCB expressing human adenovirus serotype 5 (AdSmCB) was constructed and delivered intramuscularly to female C57BL/6 mice in a heterologous prime and boost vaccine with recombinant protein. Vaccine induced immunity was described and subsequent protection from parasite infection was assessed by analysing parasite burden and liver pathology. FINDINGS: Substantially higher humoral and cell-mediated immune responses, consisting of IgG2c, Th1 effectors, and polyfunctional CD4+ T cells, were induced by the heterologous administration of AdSmCB when compared to the other regimens. Though immune responses favoured Th1 immunity, Th2 responses provided by SmCB protein boosts were maintained. This mixed Th1/Th2 immune response resulted in significant protection from S. mansoni infection comparable to other vaccine formulations which are in clinical trials. Schistosomiasis associated liver pathology was also prevented in a murine model. INTERPRETATION: Our study provides missing preclinical data supporting the use of adenoviral vectoring in vaccines for S. mansoni infection. Our vaccination method significantly reduces parasite burden and its associated liver pathology - both of which are critical considerations for this helminth vaccine. FUNDING: This work was supported by the Canadian Institutes of Health Research, R. Howard Webster Foundation, and the Foundation of the McGill University Health Centre.

Case Report: A Neuro-Ophthalmological Assessment of Vision Loss in a Pediatric Case of McCune-Albright Syndrome.

Patients diagnosed with McCune-Albright Syndrome (MAS) frequently manifest craniofacial fibrous dysplasia (FD). Craniofacial FD can impinge nerve fibers causing visual loss as well as craniofacial pain. Surgical decompression of affected nerves is performed, with variable efficacy, in an attempt to restore function or alleviate symptoms. Here, we present a case of a 12-year-old MAS patient with visual deficits, particularly in the left eye (confirmed by enlarged blind spots on Goldmann visual field testing), and craniofacial pain. Decompression surgery of the left optic nerve mildly improved vision, while persistent visual deficits were noted at a 3-month follow-up assessment. An in-depth, imaging-based evaluation of the visual system, including the retinal nerve fiber layer, optic nerves, and central nervous system (CNS) visual pathways, revealed multiple abnormalities throughout the visual processing stream. In the current FD/MAS patient, a loss of white matter fiber density within the left optic radiation and functional changes involving the left primary visual cortex were observed. Aberrant structural and functional abnormalities embedded within central visual pathways may play a role in facilitating deficits in vision in FD/MAS and contribute to the variable outcome following peripheral nerve decompression surgery.

Correction: Vaccination against the digestive enzyme Cathepsin B using a YS1646 Salmonella enterica Typhimurium vector provides almost complete protection against Schistosoma mansoni challenge in a mouse model.

[This corrects the article DOI: 10.1371/journal.pntd.0007490.].

Therapeutic activity of a Salmonella-vectored Schistosoma mansoni vaccine in a mouse model of chronic infection.

Schistosomiasis is an important fresh-water-borne parasitic disease caused by trematode worms of the genus Schistosoma. With > 250 million people infected worldwide and approximately 800 million people at risk, the World Health Organization considers schistosomiasis to be the most important human helminth infection. Several prophylactic non-living vaccines are in pre-clinical and clinical development, but only one has been assessed for therapeutic effect in an animal model with modest results. Live attenuated Salmonella have multiple potential advantages as vaccine vectors. We have engineered an attenuated Salmonella enterica Typhimurium strain (YS1646) to produce a vaccine that targets the parasite digestive enzyme Cathepsin B (CatB). A multi-modality immunization schedule was used in chronically infected mice that included three oral (PO) doses of this CatB-bearing YS1646 strain on days one, three, and five as well as an intramuscular (IM) dose of recombinant CatB on day one. Parasite burden (worm count, intestinal and liver egg numbers) were 46.5 - 50.3% lower than in control animals 1 month post-vaccination and relative reductions further increased to 63.9 - 73.3% at 2 months. Serum anti-CatB IgG increased significantly after vaccination with the development of a more balanced TH1/TH2 pattern of response (ie: a shift in the IgG1:IgG2c ratio). Compared to control animals, a broad and robust CatB-specific cytokine/chemokine response was seen in splenocytes isolated 1 month post-vaccination. A vaccine that has both prophylactic and therapeutic activity would be ideal for use in conjunction with mass treatment campaigns with praziquantel in schistosome-endemic countries.

Complex Fistula Formations After Orbital Fracture Repair With Teflon: A Review of 3 Case Reports.

ABSTRACT: The authors present 3 unique cases of complex fistula formations because of orbital fracture repair with a Teflon (polytetrafluroethylene) implant. A 26-year-old man presented with dacryocystitis and a cutaneous fistula 8 years after left orbital floor and medial wall fracture repair with a Teflon implant. A 46-year-old woman suffered orbital trauma after a motor vehicle accident as a teenager and the fracture was repaired with Teflon implant. Thirty-two years later, she presented with lower eyelid fistula, ectropion, and retraction. A 65-year-old woman also previously had Teflon implants for the repair of her left inferior and lateral orbital rim after a motor vehicle accident. Twenty-five years later, she presented with chronic infections involving the repaired areas, as well as left lower lid ectropion and fistula formation. The woven material nature of Teflon acted as a nidus for infection, inflammation, and led to complex cutaneous fistula formations in these patients.

Adjuvanted Schistosoma mansoni-Cathepsin B With Sulfated Lactosyl Archaeol Archaeosomes or AddaVax™ Provides Protection in a Pre-Clinical Schistosomiasis Model.

Schistosomiasis threatens 800 million people worldwide. Chronic pathology manifests as hepatosplenomegaly, and intestinal schistosomiasis caused by Schistosoma mansoni can lead to liver fibrosis, cirrhosis, and blood in the stool. To assist the only FDA-approved drug, praziquantel, in parasite elimination, the development of a vaccine would be of high value. S. mansoni Cathepsin B (SmCB) is a well-documented vaccine target for intestinal schistosomiasis. Herein, we test the increased efficacy and immunogenicity of SmCB when combined with sulfated lactosyl archaeol (SLA) archaeosomes or AddaVax™ (a squalene based oil-in-water emulsion). Both vaccine formulations resulted in robust humoral and cell mediated immune responses. Impressively, both formulations were able to reduce parasite burden greater than 40% (WHO standard), with AddaVax™ reaching 86.8%. Additionally, SmCB with both adjuvants were able to reduce granuloma size and the amount of larval parasite hatched from feces, which would reduce transmission. Our data support SmCB as a target for S. mansoni vaccination; especially when used in an adjuvanted formulation.

Supernumerary Lacrimal Caruncle: A Case Series.

A 12-year-old boy and 63-year-old woman were incidentally found to have a solitary, well-defined, raised, ovoid lesion involving the inferomedial palpebral conjunctiva. Both lesions were separate from the lacrimal caruncle with normal conjunctiva surrounding the lesions. Excisional biopsies were consistent with caruncular tissue. In the English literature, supernumerary lacrimal caruncle has only been previously described in adults despite the congenital nature of the lesion.

Vaccination against the digestive enzyme Cathepsin B using a YS1646 Salmonella enterica Typhimurium vector provides almost complete protection against Schistosoma mansoni challenge in a mouse model.

Schistosoma mansoni threatens hundreds of millions of people in >50 countries. Schistosomulae migrate through the lung and adult worms reside in blood vessels adjacent to the intestinal mucosa. Current candidate vaccines aren't designed to elicit a mucosal response. We have repurposed an attenuated Salmonella enterica Typhimurium strain (YS1646) to produce such a vaccine targeting Cathepsin B (CatB), a digestive enzyme important for parasite survival. Promoter-Type 3 secretory signal pairs were screened for protein expression in vitro and transfected into YS1646 to generate candidate vaccine strains. Two strains were selected for in vivo evaluation (nirB_SspH1 and SspH1_SspH1). Female C57BL/6 mice were immunized twice, 3 weeks apart, using six strategies: i) saline gavage (control), ii) the 'empty' YS1646 vector orally (PO) followed by intramuscular (IM) recombinant CatB (20µg IM rCatB), iii) two doses of IM rCatB, iv) two PO doses of YS1646-CatB, v) IM rCatB then PO YS1646-CatB and vi) PO YS1646-CatB then IM rCatB. Serum IgG responses to CatB were monitored by ELISA. Three weeks after the second dose, mice were challenged with 150 cercariae and sacrificed 7 weeks later to assess adult worm and egg burden (liver and intestine), granuloma size and egg morphology. CatB-specific IgG antibodies were low/absent in the control and PO only groups but rose substantially in other groups (5898-6766ng/mL). The highest response was in animals that received nirB_SspH1 YS1646 PO then IM rCatB. In this group, reductions in worm and intestine/liver egg burden (vs. control) were 93.1% and 79.5%/90.3% respectively (all P < .0001). Granuloma size was reduced in all vaccinated groups (range 32.9-52.8 x103µm2) and most significantly in the nirB_SspH1 + CatB IM group (34.7±3.4 x103µm2vs. 62.2±6.1 x103µm2: vs. control P < .01). Many eggs in the vaccinated animals had abnormal morphology. Targeting CatB using a multi-modality approach can provide almost complete protection against S. mansoni challenge.

Objective Brow Height Measurements Following Pretrichial Brow Lift and Upper Lid Blepharoplasty.

BACKGROUND: As the ptotic brow drops below the supraorbital rim, it can exacerbate dermatochalasis by pushing the adjacent skin of the upper lid further down. AIM: The purpose of this study was to evaluate the outcomes associated with a combined pretrichial brow lift and upper lid blepharoplasty in patients with dermatochalasis and mild to moderate brow ptosis. MATERIALS AND METHODS: A retrospective case series of 46 patients with dermatochalasis and mild to moderate brow ptosis treated with a combined, bilateral pretrichial brow lift and upper lid blepharoplasty from January 2008 to December 2011. Main outcome measures included measurements of brow lift at 3 months post-operatively, complications encountered, patient satisfaction and surgeon satisfaction. RESULTS: Outcomes from 46 patients were evaluated. The mean brow lift was 1.85 mm at the lateral canthus, 1.54 mm at the lateral limbus, 1.31 mm at the mid-pupil, and 1.07 mm at the medial limbus. Brow lift at the lateral canthus was significantly more elevated than at the medial limbus (P < 0.001). Minor complications were encountered in seven of 46 patients (15.2%). Mean patient satisfaction score was 3.20 and surgeon satisfaction 3.24 (max = 4, very satisfied). CONCLUSIONS: The modified pretrichial brow lift offered effective lateral lift that complements an upper lid blepharoplasty. This technique was met with a high degree of patient and surgeon satisfaction, and had a minimal complication profile.

Assessment of Office-Based Practice Patterns on Protective Eyewear Counseling for Patients With Monocular Vision.

PURPOSE: To investigate the practice patterns of office-based counseling on the importance of protective eyeglasses in monocular patients and to offer our counseling recommendations. METHODS: In this cross-sectional study, data were collected in the form of surveys. Surveys were administered at an oculoplastic ophthalmology clinic in Michigan. Inclusion criteria included adults with vision of 20/400 or worse in only 1 eye. Survey questions were focused on whether patients with monocular vision recall being previously counseled by their primary ophthalmologist about wearing eye protection. RESULTS: A total of 60 surveys were completed. The average age was 62.2 years old (range: 23-90 years old). Of the completed surveys, 56.7% (34/60) did not recall receiving education about wearing protective glasses over their better seeing eye, while 35.0% (21/60) recalled having received education from their referring ophthalmologist about eye protection, and 8.3% (5/60) were uncertain about receiving eye protection counseling. Twenty (33.3%) patients reported the reason for decreased vision. Of those, 35% (7/20) of patients reported monocular vision resulting from trauma, while 65% (13/20) reported vision loss due to other reasons. There was no significant difference in recall of receiving counseling about the importance of eye protection between the 2 groups (p = 0.74). CONCLUSIONS: The results of this study highlight the current counseling short-comings, as more than half (56.7%) of patients surveyed did not recall being counseled on the importance of protecting their better seeing-eye, or ways of doing so. More counseling on protective eyewear needs to be incorporated into the preferred practice pattern for care of patients with monocular visual impairment because these patients are vulnerable to the devastating consequences of complete blindness as a result of an injury to their functioning eye.

Alphasphere as a successful ocular implant in primary enucleation and secondary orbital implant exchange.

PURPOSE: To describe the surgical technique for a novel poly-HEMA (2-hydroxyethyl methacralate)[PHEMA] implant (Alphasphere, Addition Technology, Des Plaines, IL) in primary enucleation and placement of secondary orbital implant. METHODS: Retrospective chart review of all patients receiving an Alphasphere implant for primary enucleation or secondary implant exchange from October 2009 to 2011. Interval follow-up was performed again on January 2013. Patient demographics, indications for surgery, and post-operative complications were reviewed. RESULTS: Twelve patients received an Alphasphere implant for primary enucleation (n = 10) or secondary exchange (n = 2), with follow-up that ranged from 2 weeks to 14 months. The study included 9 adult and 3 pediatric patients with a mean age of 40 years, range 8-82 years. The indication for enucleation included: painful blind eye (n = 9), enophthalmos with difficult prosthesis fit in cases of secondary implant exchange (n = 2), and prophylaxis for sympathetic ophthalmia (n = 1). Only one patient required removal of the implant, due to a sinus infection with subsequent extrusion of the implant. Otherwise, the only other complication experienced was slight implant migration (n = 1). CONCLUSION: This initial report indicates that Alphasphere can be successfully used in the management of an anophthalmic socket. The advantages of the Alphasphere implant include: it does not require tissue wrapping, extraocular muscles can be directly sutured to the implant, it maintains a smooth surface to limit risk of exposure due to conjunctival breakdown, and undergoes anterior orbital fibrovascular ingrowth which optimizes prosthesis location and socket motility.

Ophthalmic and systemic findings in interstitial deletions of chromosome 14q: a case report and literature review.

We report a patient with clinical anophthalmia, partial eyelid fusion and a hypoplastic socket on the right. The left eye has microphthalmia involving the anterior and posterior segments, microcornea, iris coloboma, chorioretinal dysgenesis, macular dysplasia, absence of retinal vessels, and optic nerve aplasia. Systemic abnormalities include microcephaly, bilateral hearing loss, and duodenal atresia. Electrophysiologic testing showed no response from either eye. Cytogenetic testing revealed a de novo interstitial deletion of chromosome 14q22.3q23.1. The literature of similar interstitial deletions and ongoing candidate gene studies are reviewed.

Cranial nerve seven palsy and its influence on meibomian gland function.

PURPOSE: To investigate a possible relationship between cranial nerve seven (CN VII) palsy and meibomian gland dysfunction. METHODS: A prospective case series of 16 patients with unilateral CN VII palsy was evaluated for meibomian gland function. Main outcome measures included the Sunnybrook Facial Grading System for CN VII palsy and a modified version of a noncontact, noninvasive meibomian gland evaluation by Arita et al., Unaffected contralateral eyes were used as the control group for comparison. RESULTS: Sixteen affected eyes were evaluated. The mean Sunnybrook Facial Grading System composite score was 34.19 ± 24 (score = -15 to 100; maximum function = 100). A paired samples t test between affected and unaffected eyes demonstrated a significant difference between mean values for tear break-up time, eyelid abnormality, meiboscore for upper eyelid, meiboscore for lower eyelid, combined meiboscore, and digital pressure. No significant difference was found for superficial punctate keratopathy nor Schirmer's test. A Pearson product-moment correlation coefficient found a significant negative correlation between the Sunnybrook Facial Grading System composite score and all aspects of meibomian gland function, except for the upper eyelid meiboscore, which only approached significance (p = 0.059). CONCLUSION: These findings suggest that a strong relationship exists between cranial nerve seven palsy and meibomian gland dysfunction. Clinical optimization of meibomian gland function may benefit cranial nerve seven palsy patients.

Asymmetric eyebrow elevation and its association with ocular dominance.

PURPOSE: To examine the relation between asymmetric eyebrow elevation and ocular dominance. METHODS: A retrospective cohort study was performed in patients who underwent bilateral upper eyelid blepharoplasty from July 2007 to May 2009. Patients with pre- and postoperative involuntary asymmetric eyebrow elevation were selected from a surgical log database for inclusion in this study. Brow asymmetry was determined by examination of preoperative and postoperative digital photographs and was defined as a measured eyebrow-height difference in conjunction with the asymmetric recruitment of the frontalis muscle. Ocular dominance was determined by using a modified Porta test. Statistical analysis was performed by using the Fisher Exact test. RESULTS: Forty-seven patients met inclusion criteria. Sixty-six percent (31 of 47) involuntarily, asymmetrically elevated the right eyebrow, and 34% (16 of 47), the left. Of the 31 patients with right eyebrow elevation, 87% (27 of 31) were right-eye dominant, and 13% (4 of 31) were left-eye dominant (p < 0.001). Among patients with asymmetric left eyebrow elevation, 62.5% (10 of 16) were left-eye dominant, whereas only 37.5% (6 of 16) patients were right-eye dominant (p < 0.001). CONCLUSION: We report for the first time that involuntary asymmetric eyebrow elevation and ocular dominance are significantly associated. The assessment of ocular dominance should be included in the pre- and postoperative evaluation of patients with asymmetric brow elevation undergoing blepharoplasty. This asymmetry and its etiology must be recognized, so that an attempt to create symmetry does not result in the overcorrection of the contralateral eyelid that may lead to complications such as lagophthalmos and exposure keratopathy.

Comprehensive, combined anterior and transcaruncular orbital approach to medial canthal ligament plication.

PURPOSE: To assess the efficacy of a comprehensive technique for correction of severe punctal and medial lower eyelid ectropion and lower eyelid retraction associated with medial canthal ligament (MCL) laxity. METHODS: A comprehensive technique that plicates the anterior and posterior crura of the MCL was performed on 8 eyelids of 6 patients with punctal ectropion and MCL laxity. Preoperative and postoperative symptoms, punctal ectropion, medial lower eyelid ectropion, lower eyelid retraction, lagophthalmos, and exposure keratopathy were evaluated. RESULTS: At an average of 13 months (range, 8-17 months), preoperative symptoms of epiphora and discomfort improved or resolved in all eyes. Punctal ectropion improved in all eyes and completely resolved in 75% of eyes. Medial lower eyelid ectropion was corrected in all eyes, when present. Lower eyelid retraction, lagophthalmos, and exposure keratopathy improved in all eyes. In 1 case, edema of the caruncle and semilunar fold persisted for 6 months. CONCLUSIONS: Combined anterior and transcaruncular MCL plication is an effective and safe procedure for addressing severe punctal and medial lower eyelid ectropion that accompanies MCL laxity and is difficult to correct by other methods. This procedure provides stable, 3-dimensional support to the medial lower eyelid and punctum.

Transcaruncular medial canthal ligament plication for repair of lower eyelid malposition.

OBJECTIVE: To evaluate the long-term efficacy of transcaruncular medial canthal ligament (MCL) plication in the treatment of eyelid malposition. METHODS: Transcaruncular MCL plication was performed on 176 eyelids of 125 patients with symptomatic ocular exposure due to lower eyelid malposition in which MCL laxity was an important component. Preoperative and postoperative ocular exposure symptoms, lower eyelid position, lagophthalmos, and keratopathy were compared. RESULTS: At an average +/- SD follow-up time of 25 +/- 27 months (range, 1-103 months), 88% of preoperative symptoms resolved or improved. Lower eyelid position (P<.001), lagophthalmos (P<.001), and keratopathy (P<.001) were significantly improved. In 11% of eyelids undergoing MCL plication as the only repair, results were comparable with those in which other repairs were performed concurrently. Complications were suture breakage in 2 cases and pyogenic granuloma in 1 case. CONCLUSIONS: Transcaruncular MCL plication is a safe and effective technique for MCL laxity that contributes to lower eyelid malposition. This minimally invasive technique achieves good functional and cosmetic outcomes by re-establishing the vectoral forces for eyelid support that are normally provided by the tripartite ligament.

Graded full-thickness anterior blepharotomy for correction of upper eyelid retraction not associated with thyroid eye disease.

PURPOSE: To evaluate the efficacy of graded full-thickness anterior blepharotomy for upper eyelid retraction of various causes not associated with Graves eye disease. METHODS: Twenty-one eyelids of 18 patients with upper eyelid retraction not caused by Graves eye disease were treated with graded full-thickness anterior blepharotomy. Preoperative and postoperative symptoms, midpupil to upper eyelid distance, lagophthalmos, and superficial punctuate keratopathy were evaluated. RESULTS: Upper eyelid retraction was due to facial nerve palsy in 4 patients (22%), overcorrected ptosis in 5 patients (28%), and cicatrix after trauma in 6 patients (33%). One patient each (6% each) had retraction from graft-versus-host disease, after blepharoplasty, and after orbicularis oculi myectomy for blepharospasm. At a mean of 10 months follow-up, presenting symptoms resolved or improved in 17 patients (94%) and remained unchanged in 1 patient (6%). Midpupil to upper eyelid distance, lagophthalmos, and superficial punctuate keratopathy all improved significantly (all p < 0.001). No surgical complications occurred. CONCLUSIONS: Graded full-thickness anterior blepharotomy is a safe, effective, and rapid technique for patients with symptomatic upper eyelid retraction due to etiologies other than Graves eye disease. This technique improves symptoms and signs of ocular exposure while addressing relative upper eyelid height symmetry and contour.