Andrew R. Harrison

Myotonic dystrophy type 2 Molecular, diagnostic and clinical spectrum

Background: Myotonic dystrophy types 1 (DM1) and 2 (DM2/proximal myotonic myopathy PROMM) are dominantly inherited disorders with unusual multisystemic clinical features. The authors have characterized the clinical and molecular features of DM2/PROMM, which is caused by a CCTG repeat expansion in intron 1 of the zinc finger protein 9 (ZNF9) gene. Methods: Three-hundred and seventy-nine individuals from 133 DM2/PROMM families were evaluated genetically, and in 234 individuals clinical and molecular features were compared. Results: Among affected individuals 90% had electrical myotonia, 82% weakness, 61% cataracts, 23% diabetes, and 19% cardiac involvement. Because of the repeat tract’s unprecedented size (mean ∼5,000 CCTGs) and somatic instability, expansions were detectable by Southern analysis in only 80% of known carriers. The authors developed a repeat assay that increased the molecular detection rate to 99%. Only 30% of the positive samples had single sizeable expansions by Southern analysis, and 70% showed multiple bands or smears. Among the 101 individuals with single expansions, repeat size did not correlate with age at disease onset. Affected offspring had markedly shorter expansions than their affected parents, with a mean size difference of −17 kb (−4,250 CCTGs). Conclusions: DM2 is present in a large number of families of northern European ancestry. Clinically, DM2 resembles adult-onset DM1, with myotonia, muscular dystrophy, cataracts, diabetes, testicular failure, hypogammaglobulinemia, and cardiac conduction defects. An important distinction is the lack of a congenital form of DM2. The clinical and molecular parallels between DM1 and DM2 indicate that the multisystemic features common to both diseases are caused by CUG or CCUG expansions expressed at the RNA level.

Experimental and Clinical Evidence for Brimonidine as an Optic Nerve and Retinal Neuroprotective Agent: An Evidence-Based Review

OBJECTIVE To review the available evidence for the neuroprotective qualities of brimonidine tartrate in optic nerve and retinal injury. METHODS References for this study were obtained by running a search of the PubMed database using keywords brimonidine, neuroprotection, ischemic optic neuropathy, and alpha2-adrenergic agonists. References focusing on ocular hypertension were excluded. RESULTS Forty-eight articles addressing 1 of 4 criteria for neuroprotection were included. The literature confirms that brimonidine therapy meets the first 3 criteria for neuroprotection: receptors on its target tissues, adequate penetration into the vitreous and retina at pharmacologic levels, and induction of intracellular changes that enhance neuronal resistance to insults or interrupt apoptosis in animal models. Brimonidine did not meet the final neuroprotective criterion of success in humans. CONCLUSIONS Experimental evidence has demonstrated that brimonidine is a potential neuroprotective agent. However, to date, clinical trials have failed to translate into similar efficacy in humans.

Perioperative visual loss in ocular and nonocular surgery

Incidence estimates for perioperative vision loss (POVL) after nonocular surgery range from 0.013% for all surgeries up to 0.2% following spine surgery. The most common neuro-ophthalmologic causes of POVL are the ischemic optic neuropathies (ION), either anterior (AION) or posterior (PION). We identified 111 case reports of AION following nonocular surgery in the literature, with most occurring after cardiac surgery, and 165 case reports of PION following nonocular surgery, with most occurring after spine surgery or radical neck dissection. There were an additional 526 cases of ION that did not specify if the diagnosis was AION or PION. We also identified 933 case reports of central retinal artery occlusion (CRAO), 33 cases of pituitary apoplexy, and 245 cases of cortical blindness following nonocular surgery. The incidence of POVL following ocular surgery appears to be much lower than that seen following nonocular surgery. We identified five cases in the literature of direct optic nerve trauma, 47 cases of AION, and five cases of PION following ocular surgery. The specific pathogenesis and risk factors underlying these neuro-ophthalmic complications remain unknown, and physicians should be alert to the potential for loss of vision in the postoperative period.

Medial rectus muscle injuries associated with functional endoscopic sinus surgery: Characterization and management

Objective To characterize and evaluate treatment options for medial rectus muscle (MR) injury associated with functional endoscopic sinus surgery (FESS). Design Retrospective interventional case series Participants A total of 30 cases were gathered from 10 centers. Methods Cases of orbital MR injury associated with FESS surgery were solicited from members of the American Society of Ophthalmic Plastic & Reconstructive Surgery (ASOPRS) through an e-mail discussion group. Main Outcome Measures Variables assessed included patient demographics, computerized tomography and operative findings, extent of MR injury and entrapment, secondary orbital/ocular injuries, initial and final ocular alignment and ductions, and interventions. Results A spectrum of MR injury ranging from simple contusion to complete MR transection, with and without entrapment, was observed. Four general patterns of presentation and corresponding injury were categorized. Conclusions Medial rectus muscle injury as a complication of FESS can vary markedly. Proper characterization and treatment are important, particularly with reference to the degree of direct MR injury (muscle tissue loss) and entrapment. Patients with severe MR disruption can benefit from intervention but continue to show persistent limitation of ocular motility and functional impairment. Prevention and early recognition and treatment of these injuries are emphasized.

Doxycycline and intracranial hypertension

The authors report seven patients from six neuro-ophthalmology referral centers who developed pseudo-tumor cerebri during treatment with doxycycline. All four female patients and one of three male patients were obese. Vision was minimally affected in most patients, but two had substantial visual acuity or visual field loss at presentation. Discontinuation of doxycycline, with or without additional intracranial pressure-lowering agents, yielded improvement, but permanent visual acuity or visual field loss occurred in five patients.

Comparison of phaco-chop, divide-and-conquer, and stop-and-chop phaco techniques in microincision coaxial cataract surgery

Purpose To compare the outcomes of coaxial microincision cataract surgery (MICS) performed with 3 phacoemulsification techniques (phaco‐chop, divide‐and‐conquer, and stop‐and‐chop) according to cataract density. Setting Bucheon St. Mary’s Hospital, College of Medicine, Catholic University of Korea, Seoul, South Korea. Design Prospective randomized clinical trial. Methods Eyes with nuclear density from grade 2 to 4 were randomly subdivided into 3 groups (phaco‐chop, divide‐and‐conquer, and stop‐and‐chop). Intraoperative measurements included ultrasound time (UST), mean cumulative dissipated energy (CDE), and balanced salt solution use. Clinical measurements included preoperative and 1 day, 1 month, and 2 month postoperative corrected distance visual acuity, central corneal thickness, and endothelial cell count. Results Intraoperative measurements showed significantly less UST, CDE, and balanced salt solution use with the phaco‐chop technique than with the divide‐and‐conquer and stop‐and‐chop techniques in the grade 4 cataract density group (P<.05). The percentage of endothelial cell loss was significantly lower in the phaco‐chop group than in the divide‐and‐conquer and stop‐and‐chop groups in the grade 4 cataract density group 2 months after cataract surgery (P<.05). Conclusions All 3 techniques may be effective for coaxial MICS in mild and moderate cataracts. However, in eyes with hard cataract having coaxial MICS, the phaco‐chop technique can be more effective for lens removal, with less corneal endothelial damage, than the divide‐and‐conquer and stop‐and‐chop techniques. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

Profile of Xeomin® (incobotulinumtoxinA) for the treatment of blepharospasm.

Even though conventional botulinum neurotoxin (BoNT) products have shown successful treatment results in patients with benign blepharospasm (BEB), the main, potential long-term side effect of BoNT use is the development of immunologic resistance due to the production of neutralizing antibody to the neurotoxin after repeated injections. Xeomin® (incobotulinumtoxinA), a unique botulinum neurotoxin type A (BoNT/A) drug free of complexing proteins otherwise contained in all conventional BoNT/A drugs, was recently approved by US Food and Drug Administration for the treatment of cervical dystonia or blepharospasm in adults. The newly approved BoNT/A drug may overcome this limitation of previous conventional products, since it contains pure neurotoxin (150 kDa) through a manufacturing process that separates it from complexing proteins such as hemagglutinins produced by fermentation of Clostridium botulinum. Many studies have also shown that Xeomin® has the same efficacy and safety profile as complexing protein-containing products such as Botox® and is exchangeable with Botox® using a simple 1:1 conversion ratio. Xeomin® represents a new treatment option for the repeated treatment of patients with blepharospasm in that it may reduce antibody-induced therapy failure. But, long-term comparative trials in naïve patients between Xeomin® and conventional BoNT/A drugs are required to confirm the low immunogenicity of Xeomin®.

Update on thyroid eye disease and management

Thyroid eye disease is a heterogeneous autoimmune orbital reaction typically manifesting in middle age. The inflammation may parallel or remain isolated from a related inflammatory cascade in the thyroid called Graves’ disease. The orbital manifestations can lead to severe proptosis, dry eyes, strabismus, and optic neuropathy. In this article, we will discuss this unique condition including the ophthalmic findings and management.

Detection by impression cytologic analysis of conjunctival intraepithelial invasion from eyelid sebaceous cell carcinoma

OBJECTIVE To demonstrate that conjunctival impression cytologic analysis can detect conjunctival intraepithelial invasion from sebaceous cell carcinoma of the eyelid. DESIGN Observational case series with cytopathologic correlation. PARTICIPANTS Four patients with unilateral blepharoconjunctivitis and biopsy-proven sebaceous cell carcinoma. METHODS Impression cytologic analysis specimens were taken from the suspicious area of the bulbar conjunctiva of each patient. Staining of the specimens was performed with a modified Papanicolaou stain. MAIN OUTCOME MEASURE Observation of the abnormal tumor cells in the collected specimens by bright field microscope. RESULTS The technique of impression cytologic analysis allowed collection and identification of abnormal tumor cells with characteristic cytoplasmic vacuoles. CONCLUSIONS Conjunctival impression cytologic analysis successfully detected the ocular surface sebaceous carcinoma cells from the eyelid. However, full-thickness biopsies are necessary to confirm the diagnosis. Judicious use of impression cytologic analysis may facilitate the detection and diagnosis of this invasive tumor.

Bilateral congenital lacrimal anlage ducts (lacrimal fistula) in a Patient With the VACTERL association.

Purpose: To present a case of bilateral congenital lacrimal anlage ducts in a patient with the VACTERL (vertebral anomalies, anal atresia, cardiac malformations, tracheoesophageal fistula, renal anomalies, and limb anomalies) association. Methods: Case report. Results: A 19-year-old man presented with intermittent facial swelling. Examination revealed bilateral lacrimal anlage ducts. The patient underwent excision of the ducts with silicone intubation. Conclusions: We add the VACTERL association to the list of systemic conditions associated with lacrimal anlage ducts.