Ilya Leyngold

Comparison of Topical Dry Eye Medications for the Treatment of Keratoconjunctivitis Sicca in a Botulinum Toxin B–Induced Mouse Model

Purpose: To compare the effects of topical dry eye medications including anti-inflammatory agents and lubricant eyedrops for the treatment of keratoconjunctivitis sicca (KCS) in a botulinum toxin B (BTX-B)-induced mouse model. Methods: CBA mice were randomized into 10 groups. The first 5 groups received a transconjunctival injection of saline into the lacrimal gland, and the remaining groups were injected with 0.05 mL of 20 mU BTX-B. Each group received treatment with 0.1% fluorometholone (FML), 0.05% cyclosporine A (CsA), a 50:50 combination of FML and CsA, artificial tears, or saline 3 days after injections. Tear production, corneal staining, and blink rate were compared in each of the 10 groups. Results: Tear production in BTX-B-injected CsA-treated, FML-treated, and combined-treated groups started to return to baseline level within 2 weeks of treatment, whereas those treated with saline or artificial tears still exhibited reduction of lacrimation up to 4 weeks after injection. Topical FML significantly reversed the staining score within 1 week of treatment. The improvement of corneal staining in BTX-B-challenged combined-treated and CsA-treated groups occurred later within 2 weeks after treatment. No significant improvement in corneal staining was observed for the BTX-B-injected mice treated with artificial tears or saline. No significant changes were noted in blink frequency between the control and study groups undergoing the various dry eye therapies. Conclusion: The therapeutic effects of dry eye medications in a BTX-B-induced mouse model of KCS are similar to the human response.

N-terminal extension changes the folding mechanism of the FK506-binding protein

Many of the protein fusion systems used to enhance the yield of recombinant proteins result in the addition of a small number of amino acid residues onto the desired protein. Here, we investigate the effect of short (three amino acid) N‐terminal extensions on the equilibrium denaturation and kinetic folding and unfolding reactions of the FK506‐binding protein (FKBP) and compare the results obtained with data collected on an FKBP variant lacking this extension. Isothermal equilibrium denaturation experiments demonstrated that the N‐terminal extension had a slight destabilizing effect. NMR investigations showed that the N‐terminal extension slightly perturbed the protein structure near the site of the extension, with lesser effects being propagated into the single α‐helix of FKBP. These structural perturbations probably account for the differential stability. In contrast to the relatively minor equilibrium effects, the N‐terminal extension generated a kinetic‐folding intermediate that is not observed in the shorter construct. Kinetic experiments performed on a construct with a different amino acid sequence in the extension showed that the length and the sequence of the extension both contribute to the observed equilibrium and kinetic effects. These results point to an important role for the N terminus in the folding of FKBP and suggest that a biological consequence of N‐terminal methionine removal observed in many eukaryotic and prokaryotic proteins is to increase the folding efficiency of the polypeptide chain.

Basal cell carcinoma and rhinophyma.

Rhinophyma, the end stage in the development of acne rosacea, is characterized by sebaceous hyperplasia, fibrosis, follicular plugging, and telangiectasia. Although it is commonly considered a cosmetic problem, it can result in gross distortion of soft tissue and airway obstruction. Basal cell carcinoma (BCC) is a rare finding in patients with rhinophyma. The objective of this study is to review the literature of BCC in rhinophyma and report on a case. A 70-year-old male presented with long-standing rosacea that resulted in a gross nasal deformity. The patient suffered from chronic drainage and recurrent infections that failed conservative treatment with oral and topical antibiotics. The patient decided to proceed with surgical intervention and underwent tangential excision and dermabrasion in the operating room. Since 1955 there have been 11 cases reported in the literature. In our case, the pathology report noted that the specimen had an incidental finding of a completely resected BCC. The patient did well postoperatively and at follow-up remains tumor-free. Despite the uncommon occurrence of BCC in resection specimens for rhinophyma, we recommend that all specimens be reviewed by a pathologist. If BCC is detected, re-excision may be necessary and careful follow-up is mandatory. Larger studies would be needed to determine the correlation between the 2 conditions.

Acute Chiasmal Abscess Resulting from Perineural Extension of Invasive Sino-Orbital Aspergillosis in an Immunocompetent Patient

OBJECTIVE Intracranially invasive sino-orbital aspergillosis is a rare entity seen predominantly in immunocompromised individuals. We report a unique case of an acute chiasmal abscess resulting from perineural extension of an indolent invasive sino-orbital aspergillosis in an immunocompetent patient. CASE DESCRIPTION A 61-year-old healthy Ukrainian man presented with severe left retro-orbital pain and a gradual ipsilateral monocular vision loss with rapid progression to a contralateral temporal visual field cut. He was found to have an intracranially invasive sino-orbital Aspergillus fumigatus infection with perineural extension along the optic nerve complicated by an acute chiasmal abscess. RESULTS The patient was managed with surgical debridement and adjuvant antifungal chemotherapy. The patients life and vision were preserved. CONCLUSIONS The case demonstrates that it is possible to successfully control advanced intracranial aspergillosis with tissue-sparing surgery and adjuvant antifungal chemotherapy in immunocompetent individuals.

Use of hyaluronic acid gel in the treatment of lagophthalmos in sunken superior sulcus syndrome.

Purpose: To evaluate the use of hyaluronic acid gel in the management of lagophthalmos in sunken superior sulcus syndrome. Introduction: Lagophthalmos associated with orbital fat atrophy and deep superior sulcus is a known entity described previously. Orbital fat atrophy results in deep superior sulcus where skin, orbicularis muscle, and orbital septum retract posteriorly in the deep superior sulcus, leading to lagophthalmos from suboptimal orbicularis function and effective skin shortening. The authors define this condition as sunken superior sulcus syndrome (SSSS) when the deep superior sulcus leads to exposure keratopathy. Thus, the syndrome consists of deep superior sulcus, lagophthalmos, and exposure keratopathy. Although the use of hyaluronic acid gel has been proposed as a management option for paralytic lagophthalmos, its application in the treatment of lagophthalmos in SSSS has not been reported. Methods: In this study, 5 patients (10 eyelids) with SSSS were injected with hyaluronic acid gel in the superior sulcus of the upper eyelid. Injected amount was titrated until the desired point was reached: complete or nearly complete eyelid closure. Results: After an average follow up of 9.5 months, lagoph thalmos improved by 2 mm or 69% (p = 0.02) on the right side and by 1 mm or 71% (p = 0.01) on the left side. Most patients also reported significantly improved ocular comfort and appearance of the superior sulcus. The only complications noted were bruising and temporary uneven contour of the upper eyelid sulcus. Conclusions: Management of lagophthalmos in SSSS with hyaluronic acid gel is an effective and safe alternative to surgery.

Intraglandular Injection of Botulinum Toxin A Reduces Tear Production in Rabbits

Purpose: To develop an animal model and investigate the dose-dependent effect of an intraglandular injection of botulinum toxin A (BTX-A) on tear production. Methods: In a volume of 0.1-ml, 0.625-, 1.25-, or 2.5-U BTX-A was injected transconjunctivally in the superolateral lobe of the lacrimal gland of adult New Zealand white female rabbits. In the contralateral lacrimal gland, 0.1 ml of 0.9% sodium chloride was injected. Prior to injection and at 1-week postinjection, photographs were taken to evaluate pre- and postoperative eyelid position. Fluorescein and Rose Bengal stain were used to evaluate the corneal surface, and Schirmer test was used to assess tear production. Results: Glands injected with the intermediate (1.25 U) and the highest (2.5 U) doses of BTX-A displayed a statistically significant decrease in tear production (p = 0.002 and 0.007, respectively) compared with the contralateral saline-injected glands at 1 week. No corneal pathologic factors from excessive dryness were observed following the injection. While postinjection ptosis was observed (p = 0.025), no difference was seen between BTX-A and saline-injected eyes. Conclusions: In rabbits, intraglandular injection of BTX-A resulted in decreased tear production at 1 week. No additional reduction in tear production was seen with a BTX-A dose greater than 1.25 U, suggesting glandular receptor saturation at this dose. Despite suppression of tear production, no corneal pathologic factors were observed. Further studies are needed to refine this animal model with the ultimate goal of determining optimum delivery route and concentration to reduction in tear production while minimizing side effects in patients.

Ipsilateral supraorbital nerve transfer in a case of recalcitrant neurotrophic keratopathy with an intact ipsilateral frontal nerve: A novel surgical technique

Purpose To report a case of regained corneal sensation and function in a patient with neurotrophic keratopathy due to direct damage to the long ciliary nerves by performing a corneal neurotization procedure using ipsilateral supraorbital nerve. Surgical technique is described in detail as well as a review of the literature on corneal neurotization. Observations A patient with devastating corneal anesthesia and poor visual acuity refractory to other treatments underwent a new surgical technique involving an ipsilateral supraorbital nerve transfer to the surrounding limbus to restore corneal sensation. At 8 months follow up, there was resolution of corneal stromal opacification documented with photographs and greatly improved corneal sensation by testing with a wisp of cotton in all 4 quadrants. Her visual acuity had improved, and at two years she was stable with even more improvement in visual acuity and ocular surface health. Conclusions and importance We present the first successful case of corneal neurotization with ipsilateral supraorbital nerve in a patient with corneal anesthesia from a local injury to the long ciliary nerves. Our case demonstrates that the described method of corneal neurotization is a viable option for patients with recalcitrant neurotrophic keratopathy and an intact ipsilateral frontal nerve.

Endoscopic Corneal Neurotization: Technique and Initial Experience

PURPOSE The authors describe a minimally invasive surgical technique to re-establish corneal sensibility in a patient with neurotrophic keratopathy with the supraorbital nerve harvested endoscopically. METHODS Pedicled contralateral supraorbital nerve was harvested endoscopically through small eyelid crease and scalp incisions and transferred to the affected eye. RESULTS Endoscopic corneal neurotization was successfully performed with restoration of corneal sensibility and corneal epithelial integrity. CONCLUSIONS The use of an endoscope allows for a minimally invasive approach to successful corneal neurotization with the supraorbital nerve.

Massive Extraocular Extension of Uveal Melanoma.

e166 Ophthal Plast Reconstr Surg, Vol. 32, No. 6, 2016 A 74-year-old white man presented 32 years after being clinically diagnosed with uveal melanoma. On examination, a necrotic, fungating mass emanated from the left orbit (Fig. 1). An orbit CT scan showed a heterogenous lesion occupying the entire orbit and engulfing a phthisical globe (Fig. 2). Systemic work-up for metastatic disease was negative. Exenteration with split-thickness skin graft was performed. Histopathologic examination showed that the orbit was effaced by sheets of malignant melanocytes (HMB-45 and S-100 positive) and necrotic tissue (Fig. 3). The surgical margins were uninvolved. The patient remained disease free at a two-year follow up.

Separate Primary Melanomas of the Bulbar Conjunctiva and Eyelid Skin: Clinical Implications of Multiple Primary Melanomas

Purpose: We report a patient with previous in situ melanoma of the forehead skin who was referred for treatment of a bulbar conjunctival melanoma and a separate superficially invasive melanoma of the eyelid skin, and we offer a review of the biological and clinical implications of patients who have multiple primary melanomas. Methods: This article offers a clinicopathological correlation with a review of the relevant literature. Results: An 80-year-old white man was referred for evaluation of a suspicious conjunctival tumor and a lower-eyelid lesion. Excisional biopsies revealed that both were primary melanomas arising within in situ disease. Over the span of 25 years, the patient had three separate foci of in situ melanoma, two of which spawned invasive melanoma. Conclusion: Separate melanomas arising from the bulbar conjunctiva and eyelid skin have rarely been reported. Multiple primary melanomas of the skin, however, are not uncommon. Based on studies of persons with multiple cutaneous melanomas, the prognosis is best predicted by the tumor with the greatest depth of invasion. Patients with multiple melanomas should be examined for dysplastic nevi, additional cutaneous melanomas, and screened periodically for future lesions. Ongoing studies enrolling patients with multiple primary melanomas are attempting to generate insights into low-penetrance susceptibility genes.