Vikram D. Durairaj

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.

Clinical features and treatment of graves ophthalmopathy in pediatric patients.

Purpose: To determine the clinical characteristics and review the frequencies of medical and surgical treatment of children with Graves ophthalmopathy. Methods: Retrospective case series identifying patients 18 years or younger in whom Graves ophthalmopathy was diagnosed from 1985 through 1999. Data also were obtained from a follow-up survey. Results: The 35 children with Graves ophthalmopathy included 27 girls (77.1%) and 8 boys (22.9%). At the time of initial ophthalmic examination, 31 patients (88.6%) were hyperthyroid, 1 (2.9%) was hypothyroid, and 3 (8.6%) were euthyroid. The mean age at diagnosis of thyroid dysfunction was 13.1 years (range, 3 to 18). The mean age at diagnosis of ophthalmopathy was 15.0 years (range, 5 to 18). No patient had compressive optic neuropathy. Thirty-one patients (88.6%) required no therapy or only supportive therapy. One patient (2.9%) required eyelid surgery and 3 (8.6%) underwent transantral orbital decompression for proptosis that caused discomfort and exposure keratitis. No patient received systemic corticosteroids or orbital radiotherapy. A follow-up survey was returned by 20 respondents at a mean follow-up of 11.0 years after the initial examination (range, 3.4 to 19.4). One patient (5.0%) had undergone eye muscle surgery. All patients stated that their vision was good, and 19 (95.0%) had no diplopia. Two patients (10.0%) reported that family members had Graves ophthalmopathy, and 12 (60.0%) had family members with thyroid dysfunction. Conclusions: The clinical manifestations of Graves ophthalmopathy are relatively less severe in pediatric patients. Surgical therapy is infrequently necessary.

Mucinous eccrine adenocarcinoma of the periocular region

Purpose: To report 4 patients with mucinous eccrine adenocarcinoma of the periocular region. Methods: Interventional case series of 4 patients with mucinous eccrine adenocarcinoma of the periocular region treated at 2 centers. Results: Two patients with mucinous eccrine adenocarcinoma of the upper eyelid, 1 with mucinous eccrine adenocarcinoma of the lower eyelid, and 1 with mucinous eccrine adenocarcinoma of the eyebrow were included in this report. The lower eyelid lesion and the eyebrow lesion recurred after Mohs micrographic surgery. Both recurrent lesions were treated with Mohs micrographic surgery and postoperative adjuvant external-beam radiation therapy. The other 2 primary tumors were treated with wide local excision with frozen section control of margins and did not recur. The follow-up time after the most recent surgical procedure ranged from 8 to 17 months (median, 12 months). Conclusions: Mucinous eccrine adenocarcinoma is a rare ocular adnexal neoplasm that can involve the eyelid and periocular skin, can be locally invasive, and has a high risk of local recurrence despite Mohs surgery.

VZV multifocal vasculopathy with ischemic optic neuropathy, acute retinal necrosis and temporal artery infection in the absence of zoster rash

We describe a 54-year-old diabetic woman who developed ischemic optic neuropathy followed by acute retinal necrosis and multiple areas of focal venous beading. Vitreous fluid contained amplifiable VZV DNA but not HSV-1, CMV or toxoplasma DNA. The clinical presentation was remarkable for jaw claudication and intermittent scalp pain, prompting a temporal artery biopsy that was pathologically negative for giant cell arteritis, but notable for VZV antigen. The current case adds to the clinical spectrum of multifocal VZV vasculopathy. The development of acute VZV retinal necrosis after ischemic optic neuropathy supports the notion that vasculitis is an important additional mechanism in the development of VZV retinal injury.

Pediatric orbital floor fractures

PURPOSE To summarize the unique aspects of orbital floor fractures in children with regard to clinical presentation, management, and outcomes. METHODS MEDLINE was searched using PubMed for English-language articles on orbital floor fractures in children. All 154 indexed articles pertaining to floor fractures in patients under 18 years of age in PubMed were reviewed. Studies looking at primarily complex fractures and case reports and studies that included pediatric patients but did not analyze them separately were excluded. Overall, 25 studies were included for the review. RESULTS Inferior trapdoor fractures with muscle and soft tissue incarceration are the most common type of orbital fracture in children (27.8%-93%). They often present uniquely with severely restricted extraocular motility and diplopia (44%-100%), nausea and vomiting (14.7-55.6%), and minimal signs of external trauma. The majority of studies (83%) that analyzed time to surgery in relation to outcomes found that children who present early after initial injury and undergo prompt surgical repair appear to recover faster and have better postoperative motility than those receiving delayed treatment. CONCLUSIONS Our understanding of pediatric orbital floor fractures continues to evolve. For young patients with symptomatic diplopia with positive forced ductions, soft tissue entrapment confirmed by computed axial tomography, and/or trapdoor fracture plus restricted ocular movement, having surgery within 2-5 days has been shown to result in better postoperative outcomes. It is recommended that surgery be considered within 48 hours of diagnosis. Long-term prospective studies are still needed to further characterize orbital floor fractures in children.

Orbital implants for fracture repair.

Purpose of review To review the latest advancements in implant materials for orbital fracture repair, including analysis of the last year in research. Recent findings Advances in the manufacture of highly biocompatible alloplastic materials offer an alternative to traditional autologous implants for orbital fracture repair. The emergence of the composite implant offers the stability and strength of traditional titanium mesh, while the porous polyethylene shell allows for greater fibrovascular integration and a potential for decreased risk of postoperative complications. Development of copolymers and biomechanical constructs for the delivery of bone stimulating proteins and stem cells serve to restore orbital volume after fracture repair through stimulation of the patients own tissue. These recent developments are promising; however, their safety and efficacy have not been verified in humans. Summary The appropriate choice of orbital implant for fracture repair ensures appropriate orbital reconstruction in an effort to alleviate diplopia, enophthalmos, orbital dystopia, and extraocular muscle restriction.

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.

Orbital decompression for the management of thyroid eye disease: An analysis of outcomes and complications.

To analyze the clinical outcomes for a large cohort of patients who underwent orbital decompression for thyroid eye disease (TED) utilizing a consistent surgical approach performed by a single surgical team.

Dry Eye Syndrome: An Update in Office Management

Dry eye syndrome is a multifactorial disease of the ocular surface and tear film that results in ocular discomfort, visual disturbances, and tear instability, with potential damage to the cornea and conjunctiva. Risk factors for dry eye syndrome include age (>50 years old), female sex, environments with low humidity, systemic medications, and autoimmune disorders. There are several treatment options that range from artificial tears to anti-inflammatory and immunosuppressant agents. Treatment of this highly prevalent condition can drastically improve the quality of life of individuals and prevent damage to the ocular surface.

Clinical features and treatment of pediatric orbit fractures.

Purpose: To describe a series of orbital fractures and associated ophthalmic and craniofacial injuries in the pediatric population. Methods: A retrospective case series of 312 pediatric patients over a 9-year period (2002–2011) with orbit fractures diagnosed by CT. Results: Five hundred ninety-one fractures in 312 patients were evaluated. There were 192 boys (62%) and 120 girls (38%) with an average age of 7.3 years (range 4 months to 16 years). Orbit fractures associated with other craniofacial fractures were more common (62%) than isolated orbit fractures (internal fractures and fractures involving the orbital rim but without extension beyond the orbit) (38%). Roof and medial wall fractures were most common (30% and 28%, respectively), followed by orbital floor (24%) and lateral wall (18%) fractures. Orbital roof fractures are the most common fracture in patients <8 years old, whereas orbital floor fractures are the most common fracture in patients older than 8 years. Eighty-seven patients (28%) underwent surgical repair. There is an increasing incidence of surgery in older patients (p = 0.02). Associated neurologic injuries were more common (23%) than associated ophthalmic injuries (20%). Conclusions: Pediatric orbit fracture patterns are dictated by the age of the patient with respect to their craniofacial morphology and mechanism of injury. Orbital roof fractures are more likely to occur in younger patients and not require surgery, whereas orbital floor fractures are more common in older patients and are more likely to require surgery.