Long-term follow-up of torpedo maculopathy: a case series and mini-review.

BACKGROUND: Torpedo maculopathy (TM) is a rare, congenital condition characterized by an oval-shaped, chorioretinal lesion in the temporal macula of unknown etiology. To our knowledge, the longest reported follow-up of TM is 5 years. Herein we report 10 years of follow-up on two patients with TM to further characterize the long-term natural history of the condition. CASE REPORTS: Two patients with torpedo maculopathy were examined at baseline and then again at 5 years and 10 years from baseline. Eyes were evaluated using color fundus photography, automated perimetry, fundus autofluorescence and spectral domain optical coherence tomography. Visual function of both patients remained stable throughout the observation period. In case 1, there was no evidence of change in lesion morphology over the 10 year observation period. Case 2 showed progression of cystic degeneration of the neurosensory retina within the torpedo lesion. Case 1 reported a history of supernumerary teeth and underwent gene sequence with deletion/duplication analyses of the APC gene but no clinically significant variants were detected. CONCLUSIONS: Our findings support the position that TM is a nonprogressive condition with long-term stability of visual function. Genetic analysis of case 1 failed to detect any association with Gardner syndrome.

Rapid and effective fusion repair of severed digital nerves using neurorrhaphy and bioengineered solutions including polyethylene glycol: A case report.

Peripheral nerve injuries (PNIs) that consist of simple nerve severance often result in severe motor impairment and permanent loss of function. Such patients face significant costs and pose major burdens to healthcare systems. Currently, the most promising surgical technique to achieve the best clinical outcome after such PNIs is immediate primary coaptation of severed nerve ends by microsutures (neurorrhaphy). However, recovery is often poor and delayed for many months due to Wallerian degeneration (WD) and slow (1-2 mm/day) axonal outgrowths from severed proximal axons that may not properly reinnervate denervated afferent/efferent targets that have atrophied. In contrast, recent pre-clinical studies using polyethylene glycol (PEG) to facilitate primary nerve repair have greatly improved the rate and extent of sensory and motor recovery and prevented much WD and muscle atrophy. That is, PEG-fused axons rapidly establish proximal-distal axoplasmic/axolemmal continuity, which do not undergo WD and maintain the structure and function of neuromuscular junction (NMJ). PEG-fused axons rapidly reinnervate denervated NMJs, thereby preventing muscle atrophy associated with monthslong denervation due to slowly regenerating axonal outgrowths. We now describe PEG-mediated fusion repair of a digital nerve in each of two patients presenting with a digital laceration resulting in total loss of sensation. The first patient's tactile perception improved markedly at 3 days postoperatively (PO). Two-point discrimination improved from greater than 10 mm at initial presentation to 4 mm at 11-week PO, and the Semmes-Weinstein monofilament score improved from greater than 6.65 to 2.83 mm, a near-normal level. The second patient had severe PO edema and scar development requiring a hand compression glove and scar massage, which began improving at 11-week PO. The sensory function then improved for 4 months PO, with both two-point discrimination and Semmes-Weinstein scores approaching near-normal levels at the final follow-up. These case study data are consistent with data from animal models. All these data suggest that PEG-fusion technologies could produce a paradigm shift from the current clinical practice of waiting days to months to repair ablation PNIs with autografts, anucleated nerve allografts, or conduits in which the patient outcome is solely dependent upon axon regeneration over months or years.

Repeatability of Goldmann tonometry performed by optometry students on glaucoma patients.

BACKGROUND: The purpose of this study was to evaluate the repeatability of masked Goldmann tonometry performed by optometry students on patients with glaucoma. METHODS: Subjects were recruited from among patients scheduled to undergo selective laser trabeculoplasty at the Rosenberg School of Optometry clinic. Each subject had masked Goldmann tonometry performed by three examiners at each office visit: two fourth professional-year optometry interns and an attending optometrist. Each examiner performed three sequential masked tonometry measurements on each eye. RESULTS: Twenty-eight interns and two optometrists performed masked Goldmann tonometry on 12 glaucoma patients. The co-efficient of variation was 9.1 per cent for the right eye and 12.1 per cent for the left eye for interns compared with 6.4 per cent right eye and 6.6 per cent left eye for optometrists. There was significant interaction between intern and patient on co-efficient of variation (two-factor analysis of variance, p = 0.005), indicating co-efficient of variation was influenced by both intern and patient factors. No such interaction was found for optometrist-performed measurements (p = 0.96). Mean interobserver difference for interns ranged between 0.9 and 3.1 mmHg, with 95 per cent limits of agreement that were proportional to mean intraocular pressure. Mean interobserver difference for optometrists ranged between 0.6 and 1.8 mmHg without proportionality bias. At higher pressure levels intern measurements became more variable and tended to overestimate optometrist measurements. CONCLUSIONS: Both intraobserver and interobserver repeatability of masked tonometry was lower for interns than experienced optometrists. Intern performance differed from optometrists in that intern measurements became more variable at higher intraocular pressure levels and were significantly influenced by patient factors. The present results support the need for trainee exposure to patients with abnormally elevated intraocular pressure. Research into factors that influence trainee Goldmann tonometry repeatability is needed.

Visual evoked potential repeatability using the Diopsys NOVA LX fixed protocol in normal older adults.

PURPOSE: The purpose of this study was to evaluate the intrasession and intersession repeatability of visual evoked potentials in normal adults over 40 years of age as recorded using the Diopsys NOVA LX fixed protocol. METHODS: Inclusion criteria were adults aged over 40 years with best corrected distance acuity of 20/40 or better in each eye. Subjects underwent three consecutive visual evoked potential examinations using the Diopsys NOVA LX fixed protocol. All examination procedures were carried out in accordance with the manufacturer recommendations. To assess intersession repeatability, nine subjects returned in 2-6 weeks for repeat examination. RESULTS: A total of 46 subjects were recruited. Mean ± SD age: 53±9 years (range: 40-84 years); 69% of subjects were female and 80% were non-white. Coefficients of variation (CVs) and intra-class correlation coefficients (ICCs) revealed greater repeatability for P100 latency (CV: 3%-7%; ICC: 0.39-0.76) than for P100 amplitude (CV: 21%-33%; ICC: 0.34-0.69) and greater repeatability for recordings made with high contrast stimuli (amplitude CV: 21%-23%; latency CV: 3%-7%) than low contrast stimuli (amplitude CV: 24%-33%; latency CV: 6%-7%). Minimum detectable change values ranged between 4.50 and 9.95 µv for amplitude and 8.16-15.26 ms for latency. Repeatability was not influenced by age, sex, or race. CONCLUSION: The Diopsys NOVA LX fixed protocol demonstrated clinically acceptable intrasession and intersession repeatability in these healthy older adults, with latency being more repeatable than amplitude and examinations employing high contrast stimuli being more repeatable than those using low contrast stimuli.

Polyethylene glycol treated allografts not tissue matched nor immunosuppressed rapidly repair sciatic nerve gaps, maintain neuromuscular functions, and restore voluntary behaviors in female rats.

Many publications report that ablations of segments of peripheral nerves produce the following unfortunate results: (1) Immediate loss of sensory signaling and motor control; (2) rapid Wallerian degeneration of severed distal axons within days; (3) muscle atrophy within weeks; (4) poor behavioral (functional) recovery after many months, if ever, by slowly-regenerating (∼1mm/d) axon outgrowths from surviving proximal nerve stumps; and (5) Nerve allografts to repair gap injuries are rejected, often even if tissue matched and immunosuppressed. In contrast, using a female rat sciatic nerve model system, we report that neurorrhaphy of allografts plus a well-specified-sequence of solutions (one containing polyethylene glycol: PEG) successfully addresses each of these problems by: (a) Reestablishing axonal continuity/signaling within minutes by nonspecific ally PEG-fusing (connecting) severed motor and sensory axons across each anastomosis; (b) preventing Wallerian degeneration by maintaining many distal segments of inappropriately-reconnected, PEG-fused axons that continuously activate nerve-muscle junctions; (c) maintaining innervation of muscle fibers that undergo much less atrophy than otherwise-denervated muscle fibers; (d) inducing remarkable behavioral recovery to near-unoperated levels within days to weeks, almost certainly by CNS and PNS plasticities well-beyond what most neuroscientists currently imagine; and (e) preventing rejection of PEG-fused donor nerve allografts with no tissue matching or immunosuppression. Similar behavioral results are produced by PEG-fused autografts. All results for Negative Control allografts agree with current neuroscience data 1-5 given above. Hence, PEG-fusion of allografts for repair of ablated peripheral nerve segments expand on previous observations in single-cut injuries, provoke reconsideration of some current neuroscience dogma, and further extend the potential of PEG-fusion in clinical practice.

Polyethylene glycol solutions rapidly restore and maintain axonal continuity, neuromuscular structures, and behaviors lost after sciatic nerve transections in female rats.

Complete severance of major peripheral mixed sensory-motor nerve proximally in a mammalian limb produces immediate loss of action potential conduction and voluntary behaviors mediated by the severed distal axonal segments. These severed distal segments undergo Wallerian degeneration within days. Denervated muscles atrophy within weeks. Slowly regenerating (∼1 mm/day) outgrowths from surviving proximal stumps that often nonspecifically reinnervate denervated targets produce poor, if any, restoration of lost voluntary behaviors. In contrast, in this study using completely transected female rat sciatic axons as a model system, we provide extensive morphometric, immunohistochemical, electrophysiological, and behavioral data to show that these adverse outcomes are avoided by microsuturing closely apposed axonal cut ends (neurorrhaphy) and applying a sequence of well-specified solutions, one of which contains polyethylene glycol (PEG). This "PEG-fusion" procedure within minutes reestablishes axoplasmic and axolemmal continuity and signaling by nonspecifically fusing (connecting) closely apposed open ends of severed motor and/or sensory axons at the lesion site. These PEG-fused axons continue to conduct action potentials and generate muscle action potentials and muscle twitches for months and do not undergo Wallerian degeneration. Continuously innervated muscle fibers undergo much less atrophy compared with denervated muscle fibers. Dramatic behavioral recovery to near-unoperated levels occurs within days to weeks, almost certainly by activating many central nervous system and peripheral nervous system synaptic and other plasticities, some perhaps to a greater extent than most neuroscientists would expect. Negative control transections in which neurorrhaphy and all solutions except the PEG-containing solution are applied produce none of these remarkably fortuitous outcomes observed for PEG-fusion.

Effects of extracellular calcium and surgical techniques on restoration of axonal continuity by polyethylene glycol fusion following complete cut or crush severance of rat sciatic nerves.

Complete crush or cut severance of sciatic nerve axons in rats and other mammals produces immediate loss of axonal continuity. Loss of locomotor functions subserved by those axons is restored only after months, if ever, by outgrowths regenerating at ∼1 mm/day from the proximal stumps of severed axonal segments. The distal stump of a severed axon typically begins to degenerate in 1-3 days. We recently developed a polyethylene glycol (PEG) fusion technology, consisting of sequential exposure of severed axonal ends to hypotonic Ca(2+) -free saline, methylene blue, PEG in distilled water, and finally Ca(2+) -containing isotonic saline. This study examines factors that affect the PEG fusion restoration of axonal continuity within minutes, as measured by conduction of action potentials and diffusion of an intracellular fluorescent dye across the lesion site of rat sciatic nerves completely cut or crush severed in the midthigh. Also examined are factors that affect the longer-term PEG fusion restoration of lost behavioral functions within days to weeks, as measured by the sciatic functional index. We report that exposure of cut-severed axonal ends to Ca(2+) -containing saline prior to PEG fusion and stretch/tension of proximal or distal axonal segments of cut-severed axons decrease PEG fusion success. Conversely, trimming cut-severed ends in Ca(2+) -free saline just prior to PEG fusion increases PEG fusion success. PEG fusion prevents or retards the Wallerian degeneration of cut-severed axons, as assessed by measures of axon diameter and G ratio. PEG fusion may produce a paradigm shift in the treatment of peripheral nerve injuries. © 2016 Wiley Periodicals, Inc.