Andrea L. Kossler

Long-term outcomes of neoadjuvant intra-arterial cytoreductive chemotherapy for lacrimal gland adenoid cystic carcinoma.

PURPOSE To compare the long-term outcomes after intra-arterial cytoreductive chemotherapy (IACC) with conventional treatment for lacrimal gland adenoid cystic carcinoma (ACC). DESIGN Retrospective case series. PARTICIPANTS Nineteen consecutive patients treated with IACC, followed by orbital exenteration, chemoradiotherapy, and intravenous chemotherapy. INTERVENTIONS Analyses of the histologic characteristics of biopsy specimens, extent of disease at the time of diagnosis, diagnostic surgical procedures, incidence of locoregional recurrences or distant metastases, disease-free survival time, response to IACC, tumor margins at definitive surgery, and toxicity and complications. MAIN OUTCOME MEASURES Disease relapse, disease-free survival, and chemotherapeutic complications. RESULTS Eight patients with an intact lacrimal artery had significantly better outcomes for survival (100% vs. 28.6% at 10 years), cause-specific mortality, and recurrences (all P = 0.002, log-rank test) than conventionally treated patients from the University of Miami Miller School of Medicine. These 8 patients (group 1) had cumulative 10-year disease-free survival of 100% compared with 50% for 11 patients (group 2) who had an absence of the lacrimal artery or deviated from the treatment protocol (P = 0.035) and 14.3% for conventionally treated patients (P<0.001). Likewise, group 2 was associated with lower cause-specific mortality than the institutional comparator group (P = 0.038). Prior tumor resection with lateral wall osteotomy, delay in IACC implementation or exenteration, and failure to adhere to protocol are risk factors for suboptimal outcomes. CONCLUSIONS Neoadjuvant IACC seems to improve overall survival and decrease disease recurrence. An intact lacrimal artery, no disruption of bone barrier or tumor manipulation other than incisional biopsy, and protocol compliance are factors responsible for favorable outcomes. The chemotoxicity complication rate is limited and manageable.

Neurostimulation of the lacrimal nerve for enhanced tear production

Purpose: To design a proof-of-concept study to assess the effect of lacrimal nerve stimulation (LNS) with an implantable pulse generator (IPG) to increase aqueous tear production. Methods: Experimental animal study design of 6 Dutch Belted rabbits. Ultra high-resolution optical coherence tomography (UHR-OCT) quantified tear production by measuring the baseline tear volume of each rabbit’s OD and OS. A neurostimulator was implanted adjacent to the right lacrimal nerve. After 2 minutes of LNS (100 &mgr;s, 1.6 mA, 20 Hz, 5–8 V), the tear volumes were measured with UHR-OCT. The change in tear volume was quantified and compared with the nonstimulated OS. Three rabbits underwent chronic LNS (100 &mgr;s, 1.6 mA, 10 Hz, 2 V) and their lacrimal glands were harvested for histopathologic analysis. Results: The UHR-OCT imaging of the OD tear volume showed a 441% average increase in tear production after LNS as a percent of baseline. After stimulation, OD had statistically significant greater increase in tear volumes than OS (p = 0.028, Wilcoxon test). Poststimulation OD tear volumes were significantly greater compared with baseline (p = 0.028, Wilcoxon test). Histopathologic examination of the lacrimal glands showed no discernible tissue damage from chronic neurostimulation. In addition, there were no gross adverse effects on the general well-being of the animals due to chronic stimulation. Conclusions: LNS with an IPG appears to increase aqueous tear production. Chronic LNS showed no histopathologic lacrimal gland damage. This study suggests that LNS is a promising new treatment strategy to increase aqueous tear production.

Electronic enhancement of tear secretion.

OBJECTIVE To study electrical stimulation of the lacrimal gland and afferent nerves for enhanced tear secretion, as a potential treatment for dry eye disease. We investigate the response pathways and electrical parameters to safely maximize tear secretion. APPROACH We evaluated the tear response to electrical stimulation of the lacrimal gland and afferent nerves in isofluorane-anesthetized rabbits. In acute studies, electrical stimulation was performed using bipolar platinum foil electrodes, implanted beneath the inferior lacrimal gland, and a monopolar electrode placed near the afferent ethmoid nerve. Wireless microstimulators with bipolar electrodes were implanted beneath the lacrimal gland for chronic studies. To identify the response pathways, we applied various pharmacological inhibitors. To optimize the stimulus, we measured tear secretion rate (Schirmer test) as a function of pulse amplitude (1.5-12 mA), duration (0.1-1 ms) and repetition rate (10-100 Hz). MAIN RESULTS Stimulation of the lacrimal gland increased tear secretion by engaging efferent parasympathetic nerves. Tearing increased with stimulation amplitude, pulse duration and repetition rate, up to 70 Hz. Stimulation with 3 mA, 500 μs pulses at 70 Hz provided a 4.5 mm (125%) increase in Schirmer score. Modulating duty cycle further increased tearing up to 57%, compared to continuous stimulation in chronically implanted animals (36%). Ethmoid (afferent) nerve stimulation increased tearing similar to gland stimulation (3.6 mm) via a reflex pathway. In animals with chronically implanted stimulators, a nearly 6 mm increase (57%) was achieved with 12-fold less charge density per pulse (0.06-0.3 μC mm(-2) with 170-680 μs pulses) than the damage threshold (3.5 μC mm(-2) with 1 ms pulses). SIGNIFICANCE Electrical stimulation of the lacrimal gland or afferent nerves may be used as a treatment for dry eye disease. Clinical trials should validate this approach in patients with aqueous tear deficiency, and further optimize electrical parameters for maximum clinical efficacy.

Enhanced Tearing by Electrical Stimulation of the Anterior Ethmoid Nerve

Purpose Electrical neurostimulation enhances tear secretion, and can be applied to treatment of dry eye disease. Using a chronic implant, we evaluate the effects of stimulating the anterior ethmoid nerve on the aqueous, lipid, and protein content of secreted tears. Methods Neurostimulators were implanted beneath the nasal mucosa in 13 New Zealand white rabbits. Stimulations (2.3–2.8 mA pulses of 75–875 μs in duration repeated at 30–100 Hz for 3 minutes) were performed daily, for 3 weeks to measure changes in tear volume (Schirmer test), osmolarity (TearLab osmometer), lipid (Oil-Red-O staining), and protein (BCA assay, mass spectrometry). Results Stimulation of the anterior ethmoid nerve in the frequency range of 30 to 90 Hz increased tear volume by 92% to 133% (P ≤ 0.01). Modulating the treatment with 50% duty cycle (3 seconds of stimulation repeated every 6 seconds) increased tear secretion an additional 23% above continuous stimulation (P ≤ 0.01). Tear secretion returned to baseline levels within 7 minutes after stimulation ended. Tear film osmolarity decreased by 7 mOsmol/L, tear lipid increased by 24% to 36% and protein concentration increased by 48% (P ≤ 0.05). Relative abundance of the lacrimal gland proteins remained the same, while several serum and corneal proteins decreased with stimulation (P ≤ 0.05). Conclusions Electrical stimulation of the anterior ethmoid nerve increased aqueous tear volume, reduced tear osmolarity, added lipid, and increased the concentration of normal tear proteins. Human studies with an intranasal stimulator should verify these effects in patients with aqueous- and lipid-deficient forms of dry eye disease.

Current Trends in Upper and Lower Eyelid Blepharoplasty Among American Society of Ophthalmic Plastic and Reconstructive Surgery Members.

PURPOSE To assess current practice patterns for management of upper and lower eyelid blepharoplasty by active American Society of Ophthalmic Plastic and Reconstructive Surgery members. METHODS An invitation to participate in a web-based anonymous survey was sent to the active American Society of Ophthalmic Plastic and Reconstructive Surgery membership via email. The survey consists of 34 questions, both multiple choice and free response, regarding upper and lower eyelid blepharoplasty surgery. Practice patterns for both aesthetic and functional blepharoplasty are assessed. RESULTS Thirty-four percent (161/472) of American Society of Ophthalmic Plastic and Reconstructive Surgery members polled responded to the survey. Members perform an average of 196 upper eyelid, 46 lower eyelid, and 53 four-eyelid blepharoplasty procedures per year, with 70% of cases being functional and 30% purely aesthetic. Most members prefer monitored care (71%) to local (21%) or general (8%) anesthesia. Eighty-nine percent of surgeons use topical antibiotics after surgery, erythromycin being the most common (51%). Fourteen percent of members use postoperative oral antibiotics, with cephalexin (81%) being most common. In upper eyelid blepharoplasty, orbicularis muscle is excised by 86% of respondents. Orbital fat is excised, when deemed appropriate, in 97% of cases, with nasal fat excised most commonly (88%). Less commonly, fat repositioning (36%) and adjunctive fat grafting (33%) are performed. In lower eyelid blepharoplasty, surgeons report using one or more of the following approaches: transconjunctival (96%), transcutaneous (82%), and both transconjunctival and transcutaneous (51%). Common adjunctive procedures include orbital fat excision (99%), fat repositioning (80%), and lateral canthal suspension (96%). Less common adjunctive procedures include laser skin resurfacing (36%) and chemical peels (29%). CONCLUSIONS This report outlines contemporary practice patterns among active American Society of Ophthalmic Plastic and Reconstructive Surgery members in the management of upper and lower eyelid blepharoplasty. It is important to quantify such data periodically to update the membership as to how this common surgical procedure is approached. This also allows eyelid surgeons to compare their practice patterns with a national group specializing in such surgery.

The Spectrum of Canthal Suspension Techniques in Lower Blepharoplasty

Abstract 1. Lateral canthal suspension is an integral adjunct to lower blepharoplasty surgery. 2. These procedures include a canthoplasty where the lateral canthal tendon and/or temporal tarsus is modified and secured to the lateral orbital rim; or a canthopexy where the canthal tendon, and/or orbicularis muscle, is plicated to the lateral orbital rim. 3. Indications for canthal suspension include preexistent lower eyelid laxity, and prevention of lower eyelid malposition. 4. In aesthetic surgery less disruption of canthal architecture/integrity is best. 5. A thorough understanding of canthal and lower eyelid anatomy is essential to avoid surgical complications. 6. A careful preoperative evaluation of the eyelid position, tone, laxity, and globe/midface configuration (orbitofacial vector) are critical to attain appropriate outcomes. 7. Familiarization with both open (involves canthal incision) and closed (no canthal incision) canthal suspension techniques provides options for the aesthetic lower eyelid surgeon. 8. The risk of postblepharoplasty lower eyelid retraction, ectropion, and rounding of the canthal angle can be reduced with lateral canthal suspension. 9. The expectations and goals of lateral canthal suspension should be discussed with each patient before surgery. Patients unhappy with this form of surgery are often difficult to manage.

Orbital and chorioretinal manifestations of Erdheim-Chester disease treated with vemurafenib

Purpose We report a patient with severe multi-organ dysfunction of unknown origin who presented with bilateral orbital and chorioretinal manifestations that led to the diagnosis of Erdheim-Chester Disease (ECD). Observations ECD is a rare, histiocytic, proliferative disorder characterized by multi-systemic organ involvement that has historically lacked effective therapy. Our patient underwent genetic testing that was positive for the BRAF V600E mutation; therefore, the patient was treated with vemurafenib. Conclusions and importance This case demonstrates the rare orbital and intraocular manifestations of ECD and the unfortunate impact of a delayed diagnosis, the importance of early gene therapy testing for management decisions, and the utilization of targeted directed therapy to improve visual outcomes and quality of life.

Disseminated silicone granulomatosis in the face and orbit

Purpose To report a case of disseminated silicone granulomatosis presenting with ptosis, proptosis and vision loss. Observations A 56-year-old female presented with ptosis, proptosis, and vision loss and was noted to have palpable, erythematous masses involving the orbit, face, trunk, and body. She had a history of bilateral silicone breast implants and cosmetic facial filler injections. Orbital biopsy demonstrated non-caseating granulomas with foreign-body giant cells and vacuoles containing material consistent with silicone. Removal of the patients breast implants and systemic immunosuppression led to dramatic granuloma regression. Conclusions Silicone can induce a severe, systemic inflammatory response and should be considered in the differential for facial and periorbital granulomas in patients with a history of silicone breast implants. Management of disseminated silicone granulomatosis is challenging and requires multimodal treatment with silicone removal and systemic immunomodulation.

Orbital, eyelid, and nasopharyngeal silicone oil granuloma presenting as ptosis & pseudo-xanthelasma

Purpose To highlight the presentation and management of a patient with eyelid, orbital and nasopharyngeal silicone oil migration through a glaucoma drainage implant presenting as pseudo-xanthelasma and ptosis. Observations A 68-year male presented with unilateral ptosis and presumed xanthelasma. He had a history of glaucoma drainage implant surgery, pseudophakia, and multiple retinal detachment repairs with silicone oil. During ptosis repair it was discovered that his presumed xanthelasma was in fact an eyelid silicone granuloma. Additional work up revealed silicone infiltration of the eyelids, orbits, and nasopharynx, resulting from emulsified silicone oil leakage through his glaucoma valve implant. Conclusions and Importance Silicone oil may emulsify with time, with potential egress via a glaucoma filtration device. Clinicians should be alert for eyelid, orbital and sinonasal findings that may indicate occult migration.

Silicone Oil–Induced Nasal Polyposis: A Case Report

W hile the precise etiology and pathophysiology of nasal polyp development remain unclear, the most widely accepted concept is that polyps are a consequence of chronic inflammation. Additional associations have been made between nasal polyps and certain fungal species, asthma, aspirin sensitivity, cystic fibrosis, and eosinophilic states. At the molecular level, type 2 helper T (TH2) cells and interleukin (IL)24, 25, and 213 seem to play a role. Here, we report an unusual cause of nasal polyposis related to silicone oil extravasation from the globe into the nasal cavity.