Malena M. Amato

Prevalence and distribution of VZV in temporal arteries of patients with giant cell arteritis

Objective: Varicella-zoster virus (VZV) infection may trigger the inflammatory cascade that characterizes giant cell arteritis (GCA). Methods: Formalin-fixed, paraffin-embedded GCA-positive temporal artery (TA) biopsies (50 sections/TA) including adjacent skeletal muscle and normal TAs obtained postmortem from subjects >50 years of age were examined by immunohistochemistry for presence and distribution of VZV antigen and by ultrastructural examination for virions. Adjacent regions were examined by hematoxylin & eosin staining. VZV antigen–positive slides were analyzed by PCR for VZV DNA. Results: VZV antigen was found in 61/82 (74%) GCA-positive TAs compared with 1/13 (8%) normal TAs (p < 0.0001, relative risk 9.67, 95% confidence interval 1.46, 63.69). Most GCA-positive TAs contained viral antigen in skip areas. VZV antigen was present mostly in adventitia, followed by media and intima. VZV antigen was found in 12/32 (38%) skeletal muscles adjacent to VZV antigen–positive TAs. Despite formalin fixation, VZV DNA was detected in 18/45 (40%) GCA-positive VZV antigen–positive TAs, in 6/10 (60%) VZV antigen–positive skeletal muscles, and in one VZV antigen–positive normal TA. Varicella-zoster virions were found in a GCA-positive TA. In sections adjacent to those containing VZV, GCA pathology was seen in 89% of GCA-positive TAs but in none of 18 adjacent sections from normal TAs. Conclusions: Most GCA-positive TAs contained VZV in skip areas that correlated with adjacent GCA pathology, supporting the hypothesis that VZV triggers GCA immunopathology. Antiviral treatment may confer additional benefit to patients with GCA treated with corticosteroids, although the optimal antiviral regimen remains to be determined.

Analysis of Varicella-Zoster Virus in Temporal Arteries Biopsy Positive and Negative for Giant Cell Arteritis

IMPORTANCE Giant cell arteritis (GCA) is the most common systemic vasculitis in elderly individuals. Diagnosis is confirmed by temporal artery (TA) biopsy, although biopsy results are often negative. Despite the use of corticosteroids, disease may progress. Identification of causal agents will improve outcomes. Biopsy-positive GCA is associated with TA infection by varicella-zoster virus (VZV). OBJECTIVE To analyze VZV infection in TAs of patients with clinically suspected GCA whose TAs were histopathologically negative and in normal TAs removed post mortem from age-matched individuals. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional study for VZV antigen was performed from January 2013 to March 2015 using archived, deidentified, formalin-fixed, paraffin-embedded GCA-negative, GCA-positive, and normal TAs (50 sections/TA) collected during the past 30 years. Regions adjacent to those containing VZV were examined by hematoxylin-eosin staining. Immunohistochemistry identified inflammatory cells and cell types around nerve bundles containing VZV. A combination of 17 tertiary referral centers and private practices worldwide contributed archived TAs from individuals older than 50 years. MAIN OUTCOMES AND MEASURES Presence and distribution of VZV antigen in TAs and histopathological changes in sections adjacent to those containing VZV were confirmed by 2 independent readers. RESULTS Varicella-zoster virus antigen was found in 45 of 70 GCA-negative TAs (64%), compared with 11 of 49 normal TAs (22%) (relative risk [RR] = 2.86; 95% CI, 1.75-5.31; P < .001). Extension of our earlier study revealed VZV antigen in 68 of 93 GCA-positive TAs (73%), compared with 11 of 49 normal TAs (22%) (RR = 3.26; 95% CI, 2.03-5.98; P < .001). Compared with normal TAs, VZV antigen was more likely to be present in the adventitia of both GCA-negative TAs (RR = 2.43; 95% CI, 1.82-3.41; P < .001) and GCA-positive TAs (RR = 2.03; 95% CI, 1.52-2.86; P < .001). Varicella-zoster virus antigen was frequently found in perineurial cells expressing claudin-1 around nerve bundles. Of 45 GCA-negative participants whose TAs contained VZV antigen, 1 had histopathological features characteristic of GCA, and 16 (36%) showed adventitial inflammation adjacent to viral antigen; no inflammation was seen in normal TAs. CONCLUSIONS AND RELEVANCE In patients with clinically suspected GCA, prevalence of VZV in their TAs is similar independent of whether biopsy results are negative or positive pathologically. Antiviral treatment may confer additional benefit to patients with biopsy-negative GCA treated with corticosteroids, although the optimal antiviral regimen remains to be determined.

Hyaluronic acid gel (Restylane) filler for facial rhytids: Lessons learned from American Society of Ophthalmic Plastic and Reconstructive Surgery member treatment of 286 patients

Purpose: To review injection techniques and patient satisfaction with injection of Restylane in various facial areas by American Society of Ophthalmic Plastic and Reconstructive Surgery members. Methods: Data from 286 patients treated with Restylane in nine American Society of Ophthalmic Plastic and Reconstructive Surgery practices were abstracted to a spreadsheet for analysis. Results: Nine practices performed Restylane injections for 8.8 months on average (range, 2 to 28 months). Average practice volume per patient was 1.2 ml (range, 0.7 to 2.1 ml). Nine of nine practices injected the nasolabial and melolabial folds, 9 of 9 practices injected the lips, and 6 of 9 injected the glabella. Only 2 of 9 practices injected other fillers concurrently. Botox was injected concurrently by 8 of 9 practices. On a scale of 1 to 10, physicians rated average patient discomfort during Restylane injection 4.6 with topical anesthesia and 2.1 with injectable lidocaine, with or without topical anesthesia. The end point for injection was determined by visual cues, volume of injection, extrusion of the product, and palpation. “Problematic” complications, including bruising, swelling, bumpiness, and redness each had an incidence of 5% or less. Patient satisfaction on a scale of 1 to 10 had an average rating of 8.1, compared with that of Botox injection (8.9), upper blepharoplasty (8.9), and collagen injection (6.6). The source of Restylane patients was estimated to be existing Botox patients (45%); existing non-Botox patients (18%); word of mouth (14%); and new patients for other services (13%). Conclusions: Injection techniques, volume, end points, and anesthesia vary for different facial areas and between practices. Patients experience mild to moderate injection discomfort that is lessened with injectable lidocaine. Self-limited problems occur in about 5% of patients. Physician-determined patient satisfaction is perceived to be higher than that of collagen injection but slightly lower than that of botulinum toxin injection. The major source of Restylane patients was from existing practice patients, especially botulinum toxin patients.

Atypical Presentations of Orbital Cellulitis Caused by Methicillin-Resistant Staphylococcus aureus

PURPOSE To evaluate the epidemiologic and clinical features of orbital cellulitis caused by methicillin-resistant Staphylococcus aureus (MRSA). DESIGN Multicenter, retrospective case series. PARTICIPANTS Fifteen patients with culture-positive MRSA orbital cellulitis. METHODS All recent cases of orbital cellulitis at several hospitals and surgical centers were reviewed, and cases with culture-positive MRSA from aspirates were identified. The data collected and analyzed retrospectively included patient demographics, medical history, presenting sign, imaging results, surgical procedure performed, surgical culture results, visual acuity at presentation and last follow-up, and duration of antibiotics. MAIN OUTCOME MEASURES Presenting sign, radiographic evidence of paranasal sinus disease, radiographic evidence of multiple orbital abscesses, presence or absence of antecedent upper respiratory infection, and final visual acuity. RESULTS Fifteen cases were identified. The mean patient age was 31.9 years (standard deviation, 24.2 years). Lid swelling was the presenting sign in 14 of 15 patients. No patients had a preceding upper respiratory infection, and only 1 patient had antecedent eyelid trauma. Only 3 of 15 patients had documented adjacent paranasal sinus disease on imaging. Lacrimal gland abscess or dacryoadenitis was the presenting finding in 5 of 15 patients. Multiple orbital abscesses were identified in 4 of 15 patients by computed tomography or magnetic resonance imaging. Fourteen of 15 cases required surgical intervention. Four of 15 cases had loss of visual acuity to light perception or worse. All 4 of these cases had a delay in referral for surgical intervention. CONCLUSIONS In these 15 patients with MRSA orbital cellulitis, the typical clinical setting of orbital cellulitis was absent; chiefly, there was no identified antecedent upper respiratory illness, nor was there a preceding traumatic injury. Lid swelling in the absence of recent upper respiratory illness, lacrimal gland focus, multiple orbital abscesses, and lack of adjacent paranasal sinus disease may be predictive factors that suggest MRSA as the causative organism of orbital cellulitis. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Trends in ophthalmic manifestations of methicillin-resistant Staphylococcus aureus (MRSA) in a northern California pediatric population

PURPOSE To determine pediatric clinical trends of ocular and periocular methicillin-resistant Staphylococcus aureus (MRSA) in a large northern California healthcare system. METHODS This study was a retrospective cross-sectional review of all pediatric cases (aged 0-18) with culture-positive ophthalmic MRSA isolates identified between January 2002 and December 2009. Medical record review included history, presentation, infection site, acquisition (community or nosocomial), antibiotic sensitivity/resistance, treatment, and clinical outcome. Incidence was classified by year, sex, and age. Parameters were analyzed for statistical significance by trend and χ(2) analysis. RESULTS A total of 399 ocular and periocular MRSA cases were included. Cases trended upward from 2002 to 2009, peaking in 2006. Of the 137 pediatric cases (0-18 years), 58% were community acquired. Conjunctivitis was the predominant presentation (40%), followed by stye/chalazion (25%), orbital cellulitis/abscess (19%), dacryocystitis (11%) and brow abscess (3%). Significant predictors for ocular infection with MRSA included male sex (61%), neonates (38%), and multiple infection sites on the body (38%). Resistance was high to bacitracin (80.9%) and ofloxacin (48.3%) but remained low for trimethoprim/sulfamethoxazole (8.7%). Topical therapy was effective in 29% of cases; oral antibiotics, in 47%. Intravenous therapy was required in 12% of cases and incision/drainage or surgery in 19%. Initial oral antibiotic treatment, primarily cephalosporins (24%), was ineffective in 37% of patients. There was a significant increase in resistance to antibiotic therapy (P < 0.001) during the study period. No patients developed permanent visual impairment. CONCLUSIONS Pediatric ocular and periocular MRSA is increasing in incidence and resistance in our patient population. Outcomes can be improved by early recognition, proper antibiotic selection, and obtaining cultures and sensitivities when resistant or severe ocular infections are present.

Use of Bioglass for Orbital Volume Augmentation in Enophthalmos: A Rabbit Model (Oryctolagus Cuniculus)

Purpose To investigate the clinical and histologic response of Novabone-C/M as an osteoproductive alloplastic implant for volume augmentation in the orbit in the treatment of enophthalmos and to compare its outcome alone versus its use in combination with autogenous bone or Medpor granules. Methods Novabone-C/M, a bioactive silicone glass material, was implanted in the subperiosteal space of the left orbit of 12 New Zealand White rabbits. The animals were divided into 3 groups, each with 4 animals, based on the material implanted in the orbit: group 1, Novabone alone; group 2, Novabone plus Medpor granules; and group 3, Novabone plus autogenous bone fragments. All rabbits were studied clinically, radiographically, and histologically at 1-, 3-, and 6-month intervals. Animals underwent preoperative and postoperative computed tomography (CT) with 3-dimensional reconstruction, proptosis measurements, and volumetric analysis. Orbit specimens were studied histologically with mineralized bone stain (MIBS) to look for bone formation, reactivity, infection, implant resorption, and migration. Results There were no signs of significant inflammation or infection. Subcutaneous migration of the implant was seen radiographically but not clinically in groups 1 and 3. Induced proptosis averaged 2.5 mm (at 1 month) and showed regression in all groups over a 6-month period but was not statistically significant. Implant volume was markedly reduced in all groups, averaging 69% in group 1, 37% in group 2, and 59% in group 3 at 6 months. New bone formation and bone remodeling was present in all 3 groups at 3 months and only in group 2 at 6 months. The rate and amount of implant remodeling and bone formation was greatest in the Novabone/Medpor group (group 2). Conclusions Bioglass particulate is biocompatible, easy to use in the orbit, and stimulates bone growth. Bioglass is associated with volume loss and migration over 6 months and may not provide adequate volume augmentation in the orbit when used alone for the treatment of enophthalmos. The duration and amount of bone formation may be enhanced when Novabone is used in conjunction with Medpor.

The smooth surface tunnel porous polyethylene enucleation implant.

BACKGROUND AND OBJECTIVE To describe early clinical results with the porous polyethylene smooth surface tunnel (SST) enucleation implant. PATIENTS AND METHODS Uncontrolled, prospective interventional case series of patients undergoing enucleation with placement of the SST implant. This implant consists of a porous polyethylene sphere with a smooth anterior surface containing pre-drilled tunnels to facilitate direct suturing of the rectus muscles to the implant without use of an implant wrap. Postoperatively, socket healing was assessed, and prosthesis and socket motility were evaluated by the surgeon using an ordinal scale (0 = no motility to 4 = excellent motility). RESULTS Thirty patients received the SST implant, with a mean follow-up of more than 23 months. Two cases of exposure occurred and were managed surgically without the need for explantation. Mean socket motility was 3.1 on a 0 to 4 ordinal scale, with mean prosthesis motility of 2.8. CONCLUSION The SST implant provides satisfactory socket motility and is generally well tolerated in the anophthalmic socket without the need for wrapping material.

Orbital rhabdomyosarcoma metastatic to the contralateral orbit: A case report

OBJECTIVE To report a rare presentation of metastatic orbital rhabdomyosarcoma and the corresponding findings on magnetic resonance imaging (MRI). DESIGN Interventional case report. RESULTS A 29-year-old white man was diagnosed with rhabdomyosarcoma of the left sinus and orbit for which he was treated with chemotherapy and radiation. Eighteen months after diagnosis, he returned with subacute right eye pain and dysmotility of his extraocular muscles. MRI revealed solitary enlargement of the right medial rectus muscle, and thyroidopathy was suspected. Over the next 2 months, symptoms progressed, and proptosis developed. MRI showed infiltration of seven extraocular muscles. A biopsy of right orbital tissues and the right medial rectus muscle was performed. Special tissue typing confirmed metastatic alveolar rhabdomyosarcoma. The patient underwent palliative radiation therapy and chemotherapy, but he ultimately died of disseminated disease. CONCLUSIONS Rhabdomyosarcoma can rarely metastasize to the extraocular muscles. Earlier recognition of orbital metastasis through radiographic and biopsy findings, along with prompt and aggressive treatment, may prevent fulminant spread of rhabdomyosarcoma.

Ophthalmic Methicillin-resistant Staphylococcus aureus Infections: Sensitivity and Resistance Profiles of 234 Isolates

To identify the sensitivity and resistance profiles of ophthalmic Methicillin-resistant Staphylococcus aureus (MRSA) in a large, diverse demographic. The electronic database of a large health maintenance organization was searched for patients who had an ophthalmic bacterial culture performed from 2002 to 2008 which grew MRSA. Data collected included culture source, sensitivity and resistance profiles, and whether the infection was community or nosocomially-acquired. In this retrospective study, not all isolates were tested for all the antibiotics. All isolates tested for vancomycin, trimethoprim/sulfamethoxazole, and rifampin were sensitive to these antibiotics and none were resistant. Gentamycin and chloramphenicol had the next highest sensitivity to resistance ratios, followed by tetracycline and trimethoprim (without sulfamethoxazole). Community acquired MRSA is becoming more frequent and the most common ophthalmic manifestation is eyelid involvement. The sensitivities to antibiotics of the ophthalmic MRSA isolates in this study are consistent with that seen in the literature.

Comparison of Revision Rates of Anterior- and Posterior-Approach Ptosis Surgery: A Retrospective Review of 1519 Cases

PURPOSE To compare revision rates for ptosis surgery between posterior-approach and anterior-approach ptosis repair techniques. METHODS This is the retrospective, consecutive cohort study. All patients undergoing ptosis surgery at a high-volume oculofacial plastic surgery practice over a 4-year period. A retrospective chart review was conducted of all patients undergoing posterior-approach and anterior-approach ptosis surgery for all etiologies of ptosis between 2011 and 2014. Etiology of ptosis, concurrent oculofacial surgeries, revision, and complications were analyzed. The main outcome measure is the ptosis revision rate. RESULTS A total of 1519 patients were included in this study. The mean age was 63 ± 15.4 years. A total of 1056 (70%) of patients were female, 1451 (95%) had involutional ptosis, and 1129 (74.3%) had concurrent upper blepharoplasty. Five hundred thirteen (33.8%) underwent posterior-approach ptosis repair, and 1006 (66.2%) underwent anterior-approach ptosis repair. The degree of ptosis was greater in the anterior-approach ptosis repair group. The overall revision rate for all patients was 8.7%. Of the posterior group, 6.8% required ptosis revision; of the anterior group, 9.5% required revision surgery. The main reason for ptosis revision surgery was undercorrection of one or both eyelids. Concurrent brow lifting was associated with a decreased, but not statistically significant, rate of revision surgery. Patients who underwent unilateral ptosis surgery had a 5.1% rate of Herings phenomenon requiring ptosis repair in the contralateral eyelid. Multivariable logistic regression for predictive factors show that, when adjusted for gender and concurrent blepharoplasty, the revision rate in anterior-approach ptosis surgery is higher than posterior-approach ptosis surgery (odds ratio = 2.08; p = 0.002). CONCLUSIONS The overall revision rate in patients undergoing ptosis repair via posterior-approach or anterior-approach techniques is 8.7%. There is a statistically higher rate of revision with anterior-approach ptosis repair.