Prospective, Randomized, Fellow Eye-Controlled Study of Postoperative Pain and Inflammation Control with an Intracanalicular Dexamethasone 0.4 mg Ophthalmic Insert Following Small Incision Lenticule Extraction.

Purpose: To compare postoperative anterior chamber inflammation, pain, and patient preference following small incision lenticule extraction (SMILE) in eyes treated with a dexamethasone 0.4 mg intracanalicular insert (DEX) or topical prednisolone acetate (PRED). Patients and Methods: In this prospective, randomized, fellow eye-controlled trial, 20 patients underwent same-day, bilateral SMILE. One randomly-selected eye of each patient received DEX placed immediately postoperatively, and the fellow eye received topical PRED tapered over 2 weeks. Postoperative evaluations were performed on day 1, week 1, month 1, and month 3. Primary outcomes included postoperative pain, incidence of anterior chamber cell and flare, and patient preference of steroid therapy. Results: No eyes in either group had any clinically evident cell or flare at any postoperative time point. Mean pain scores (0-10 by subjective report) and incidence of any pain were statistically similar at all postoperative visits. Uncorrected distance visual acuity improved in all eyes, 91% of which achieved 20/25 or better. No eyes lost any lines of corrected distance visual acuity. Three eyes developed a steroid-related rise in intraocular pressure, all of which resolved with 2 of the 3 eyes requiring topical therapy. At 1 week, 1 month, and 3 months, 70%, 65%, and 53% of patients preferred DEX over PRED therapy, respectively. Conclusion: The DEX insert was preferred by more patients and controlled postoperative inflammation and pain comparably to topical PRED in eyes undergoing SMILE. There were no statistically significant differences in visual outcomes between the two groups.

Diagnosis and management of postrefractive surgery ectasia.

Postrefractive surgery ectasia is a serious, sight-threatening complication seen after the following procedures: laser in situ keratomileusis, photorefractive keratectomy, small-incision lenticule extraction, radial keratotomy, and/or arcuate keratotomy. Specific risk factors may include age, corneal thickness, degree of refractive error, corneal topographic changes including irregular astigmatism, percent tissue ablation, and residual stromal bed. Biomarkers may be a new option to help indicate who is at greatest risk for ectasia. Visual aids including spectacles or contacts lenses are often required to achieve optimal vision. Collagen crosslinking is the only treatment believed to stop progression of ectasia and prevent keratoplasty. Other surgical options may include topography-guided phototherapeutic keratectomy and intrastromal corneal ring segments. Ultimately, an "ounce of prevention is a pound of cure," so careful preoperative screening and ultimately offering the safest and most effective treatments for patients is arguably the most important job of the refractive surgeon.

Congenital Tonic Pupils Associated With Congenital Central Hypoventilation Syndrome and Hirschsprung Disease.

Autonomic dysfunction can be associated with pupillary abnormalities. We describe a rare association of tonic pupils, congenital central hypoventilation syndrome, and Hirschsprung disease in a newborn with a mutation in the PHOX2B gene, a key regulator of neural crest cells. Hirschsprung disease is characterized by the congenital absence of neural crest-derived intrinsic ganglion cells. Tonic pupils may result from an abnormality of the ciliary ganglion, another structure of neural crest origin. The close association of these conditions in this child suggests a common abnormality in neural crest migration and differentiation.

SnapShot-Seq: a method for extracting genome-wide, in vivo mRNA dynamics from a single total RNA sample.

mRNA synthesis, processing, and destruction involve a complex series of molecular steps that are incompletely understood. Because the RNA intermediates in each of these steps have finite lifetimes, extensive mechanistic and dynamical information is encoded in total cellular RNA. Here we report the development of SnapShot-Seq, a set of computational methods that allow the determination of in vivo rates of pre-mRNA synthesis, splicing, intron degradation, and mRNA decay from a single RNA-Seq snapshot of total cellular RNA. SnapShot-Seq can detect in vivo changes in the rates of specific steps of splicing, and it provides genome-wide estimates of pre-mRNA synthesis rates comparable to those obtained via labeling of newly synthesized RNA. We used SnapShot-Seq to investigate the origins of the intrinsic bimodality of metazoan gene expression levels, and our results suggest that this bimodality is partly due to spillover of transcriptional activation from highly expressed genes to their poorly expressed neighbors. SnapShot-Seq dramatically expands the information obtainable from a standard RNA-Seq experiment.

Cobalt-chromium toxic retinopathy case study.

PURPOSE: To report the clinical case of a 65-year-old male who developed retinal dysfunction following cobalt-chromium toxicity. METHODS: A review of the clinical, haematological, radiological and electrophysiological investigations into a single patient was performed in order to form a case report. RESULTS: A 65-year-old male presented to his ophthalmologist with a 1-year history of worsening vision on the background of a multisystem illness including motor axonopathy, pericardiomyopathy and bulbar palsy. His medical history included hypertension, hypercholesterolaemia and a metallic hip prosthesis. Ocular examination revealed significantly reduced visual acuity bilaterally along with very poor colour vision. Cornea, fundi and optic discs all appeared normal. Bilateral moderate nuclear sclerosis was noted. Basic investigations including mitochondrial studies, auto-immune screen and MRI of brain were unremarkable. Further investigations showed significantly elevated plasma cobalt and chromium levels. Electrophysiological studies revealed an abnormality in all phases of the ERG including a negative b-waveform, suggestive of inner retinal pathology. Following subsequent revision of the hip, cobalt and chromium levels decreased and the patient's vision improved. Further electrophysiological testing indicates a persistent ERG abnormality despite a significant improvement in both the patient's visual acuity and colour vision. CONCLUSIONS: These results suggest that cobalt-chromium toxicity can cause inner retinal dysfunction.

Successful separation of the conjoined thecal sac with an epidermal cyst in pygopagus twins.

Pygopagus conjoined twins are very rare, and half of all pygopagus twins have other anomalies. This report describes the successful surgical separation of pygopagus twins who had a conjoined thecal sac and an epidermal cyst. Meticulous preoperative planning, development of a model simulator, multispecialty teamwork, and a staged surgery contributed to a successful outcome.

Neuronal expression of TATA box-binding protein containing expanded polyglutamine in knock-in mice reduces chaperone protein response by impairing the function of nuclear factor-Y transcription factor.

The polyglutamine diseases consist of nine neurodegenerative disorders including spinocerebellar ataxia type 17 that is caused by a polyglutamine tract expansion in the TATA box-binding protein. In all polyglutamine diseases, polyglutamine-expanded proteins are ubiquitously expressed throughout the body but cause selective neurodegeneration. Understanding the specific effects of polyglutamine-expanded proteins, when expressed at the endogenous levels, in neurons is important for unravelling the pathogenesis of polyglutamine diseases. However, addressing this important issue using mouse models that either overly or ubiquitously express mutant polyglutamine proteins in the brain and body has proved difficult. To investigate the pathogenesis of spinocerebellar ataxia 17, we generated a conditional knock-in mouse model that expresses one copy of the mutant TATA box-binding protein gene, which encodes a 105-glutamine repeat, selectively in neuronal cells at the endogenous level. Neuronal expression of mutant TATA box-binding protein causes age-dependent neurological symptoms in mice and the degeneration of cerebellar Purkinje cells. Mutant TATA box-binding protein binds more tightly to the transcription factor nuclear factor-Y, inhibits its association with the chaperone protein promoter, as well as the promoter activity and reduces the expression of the chaperones Hsp70, Hsp25 and HspA5, and their response to stress. These findings demonstrate how mutant TATA box-binding protein at the endogenous level affects neuronal function, with important implications for the pathogenesis and treatment of polyglutamine diseases.

Measuring depth of injury (DOI) in an isolated rabbit eye irritation test (IRE) using biomarkers of cell death and viability.

While DOI is a mechanistic correlate to the ocular irritation response, attempts to measure DOI in alternative tests have been limited to qualitative histopathologic assessment by veterinarian pathologists. The purpose of this study was to determine whether DOI could be measured objectively by fluorescent staining for biomarkers of cell death and viability using an ex vivo isolated rabbit eye (IRE) test. A panel of nine materials characterized by in vivo DOI were selected that caused slight (3% acetic acid and 5% SDS), mild (acetone, sodium hypochlorite and 10% acetic acid), moderate (cyclohexanol and parafluoroanaline) and severe (8% sodium hydroxide and 10% benzalkonium chloride) irritation. Materials were then tested using a modified IRE test with 3h recovery and then processed for cyrosectioning and staining using a TUNEL assay to detect cell death, phalloidin to detect intracellular f-actin and DAPI staining to detect nuclei. Control eyes treated with water showed intense phalloidin staining of the corneal epithelium and stromal keratocytes but no TUNEL labeling. In general, eyes treated with mild, moderate and severe irritants showed regions of TUNEL labeled epithelial and keratocyte nuclei with no phalloidin stain overlying phalloidin stained, undamaged cells. DOI measurements showed that slight irritants damaged<40% of the epithelium, mild and moderate irritants damaged>50% of the epithelium, extending at times into the anterior stroma (<20%), and the severe irritant damaged>50% of the stroma. Regression analysis between ex vivo and in vivo DOI showed a significant (p<0.007) correlation (r=0.785). These data suggest that fluorescent staining of fixed and sectioned tissue using biomarkers can be used to objectively identify the depth of injury caused by ocular irritants.