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.

Association of Diopsys® Short-duration Transient Visual Evoked Potential Latency with Visual Field Progression in Chronic Glaucoma.

AIM: To determine the association of Diopsys® NOVA-LX amplitude and latency abnormality scores with perimetric staging of chronic glaucoma, and to explore potential single-visit short-duration transient visual evoked potential (SD-tVEP) trend detection ability utilizing Humphrey 30-2 field progression data. MATERIALS AND METHODS: Setting: Glaucoma subspecialty clinic. Participants: Treated adult chronic glaucoma patients undergoing SD-tVEP evaluation. Main outcome measures: (1) Proportion of eyes designated as suspect or abnormal by the NOVA-LX multifactorial algorithm were determined as a function of glaucoma severity using the most recent Humphrey visual field analyzer (HVFA) 30-2 field. (2) Association between long-term HVFA-guided progression analysis (GPA) annual slopes and SD-tVEP abnormality was assessed to determine whether a single VEP test might help to identify eyes more prone to progressive visual field (VF) loss. RESULTS: One hundred and thirty-three eyes of 84 patients (mean age 68 years) were analyzed. The SD-tVEP abnormality increased proportionately with severity of VF loss under high-contrast (Hc) test conditions for both latency (p = 0.001) and amplitude (p < 0.01). The HVFA progression analysis printouts existed for 91 eyes (mean 12.3 fields per eye/range 5-18). Nearly three-quarters (72.5%) of eyes with mean annual HVFA progression >0.7 dB/year (n = 29) had single-visit VEP latency abnormalities. Fewer than half (46.7%) of the remainder (n = 62) showed latency abnormality. Mean progression for eyes with abnormal vs normal VEP latency was -0.87 ± 0.3 dB/year vs -0.32 ± 0.4 dB/year. CONCLUSION: Diopsys NOVA-LX Hc latency abnormality shows strong association with VF loss among a diverse population of clinical patients undergoing active treatment for chronic glaucoma, and appears likely to afford clinically useful trend-detecting test. CLINICAL SIGNIFICANCE: The SD-tVEP has the potential to serve as a single-visit clinical indicator to identify glaucoma patients at high risk for VF progression.How to cite this article: Trevino R, Sponsel WE, Majcher CE, Allen J, Rabin J. Association of Diopsys® Short-duration Transient Visual Evoked Potential Latency with Visual Field Progression in Chronic Glaucoma. J Curr Glaucoma Pract 2018;12(1):29-35.

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.

A Rare Cause of Pyogenic Flexor Tenosynovitis: Nocardia nova.

Infection complicates approximately 5% of open trigger digit releases. Both superficial and deep infections may occur. We present a unique case of a cactus farmer who underwent an uneventful thumb trigger finger release and subsequently developed pyogenic flexor tenosynovitis and acute carpal tunnel syndrome resulting from Nocardia nova infection.

Use of non-selective ß-blockers is associated with decreased tumor proliferative indices in early stage breast cancer.

Previous studies suggest beta-adrenergic receptor (ß-AR) antagonists (ß-blockers) decrease breast cancer progression, tumor metastasis, and patient mortality; however the mechanism for this is unknown. Immunohistochemical analysis of normal and malignant breast tissue revealed overexpression of ß1-AR and ß3-AR in breast cancer. A retrospective cross-sectional study of 404 breast cancer patients was performed to determine the effect of ß-blocker usage on tumor proliferation. Our analysis revealed that non-selective ß-blockers, but not selective ß-blockers, reduced tumor proliferation by 66% (p < 0.0001) in early stage breast cancer compared to non-users. We tested the efficacy of propranolol on an early stage breast cancer patient, and quantified the tumor proliferative index before and after treatment, revealing a propranolol-mediated 23% reduction (p = 0.02) in Ki67 positive tumor cells over a three-week period. The anti-proliferative effects of ß-blockers were measured in a panel of breast cancer lines, demonstrating that mammary epithelial cells were resistant to propranolol, and that most breast cancer cell lines displayed dose dependent viability decreases following treatment. Selective ß-blockers alone or in combination were not as effective as propranolol at reducing breast cancer cell proliferation. Molecular analysis revealed that propranolol treatment of the SK-BR-3 breast cancer line, which showed high sensitivity to beta blockade, led to a reduction in Ki67 protein expression, decreased phosphorylation of the mitogenic signaling regulators p44/42 MAPK, p38 MAPK, JNK, and CREB, increased phosphorylation of the cell survival/apoptosis regulators AKT, p53, and GSK3ß. In conclusion, use of non-selective ß-blockers in patients with early stage breast cancer may lead to decreased tumor proliferation.

The Effectiveness of an Educational Game for Teaching Optometry Students Basic and Applied Science.

PURPOSE: To compare the effectiveness of an educational board game with interactive didactic instruction for teaching optometry students elements of the core optometric curriculum. METHODS: Forty-two optometry students were divided into two GPA-matched groups and assigned to either 12 hours of game play (game group) or 12 hours of interactive didactic instruction (lecture group). The same material from the core optometric curriculum was delivered to both groups. Game play was accomplished via an original board game. Written examinations assessed change in knowledge level. A post-intervention opinion survey assessed student attitudes. RESULTS: There was no significant difference in pre- or post-intervention test scores between the lecture and game groups (Pre-test: p = 0.9; Post-test: p = 0.5). Post-intervention test scores increased significantly from baseline (Game group: 29.3% gain, Didactic group: 31.5% gain; p<0.001 for each). The score increase difference between groups was not statistically significant (p = 0.6). The post-intervention attitude survey did not reveal any significant between group differences (p = 0.5). CONCLUSIONS: Our results indicate that an educational game and interactive didactic instruction can be equally effective in teaching optometry students basic and applied science. Furthermore, both modes of instruction have the potential to be equally engaging and enjoyable experiences.

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.

Change in intraocular pressure during scleral depression / Cambio en la presión intraocular durante la depresión escleral

Purpose: Manometric studies have found that intraocular pressure (IOP) rises 116–350mmHg during scleral depression in surgical settings. No information is available regarding the effect of scleral depression on IOP in routine clinical settings. The aim of this study is to quantify the change in IOP that occurs when scleral depression is performed on normal eyes in a routine clinical setting. Methods: A total of 28 eyes from 28 normal subjects were included. Tono-Pen tonometry was performed while scleral depression was performed in each of the two quadrants: superotemporal (ST) and inferonasal (IN). A post-procedure IOP measurement was obtained following each scleral depression examination. Both ST and IN quadrants were tested on all eyes, with the quadrant tested first chosen at random (15 ST, 13 IN). Results: The mean IOP during scleral depression was 65.3mmHg ST and 47.8mmHg IN, with a maximum recorded IOP of 88mmHg. The mean change in IOP for the ST quadrant was 51.9±17.3mmHg and 46.4±16.0mmHg for the right and left eyes, respectively. The mean change in IOP for the IN quadrant was 45.3±22.7mmHg and 16.8±15.8mmHg for the right and left eyes, respectively. Conclusions: Scleral depression as performed in a routine office setting produces wide fluctuations in IOP and may impair ocular perfusion. Additional studies are needed to determine the long-term consequences of routine scleral depression (AU)

Objetivo: Los estudios manométricos han hallado que la presión intraocular (PIO) se eleva de 116 a 350mmHg durante la depresión escleral en el ámbito quirúrgico. No se dispone de información en relación al efecto de la depresión escleral sobre la PIO en la rutina del ámbito clínico. El objetivo de estudio es la cuantificación del cambio en la PIO que se produce cuando se realiza la depresión escleral en ojos normales en un escenario clínico rutinario. Métodos: Se incluyeron un total de 28 ojos de 28 sujetos normales. Se realizó una tonometría Tono-Pen, mientras que la depresión escleral se llevaba a cabo en dos cuadrantes: superotemporal (ST) e inferonasal (IN). Se realizó una medición de la PIO tras llevar a cabo cada depresión escleral. Se realizaron las medidas en ambos cuadrantes ST e IN en todos los ojos, eligiéndose el primer cuadrante a testear al azar (15 ST, 13 IN). Resultados: La PIO media durante la depresión escleral fue de 65,3mmHg ST y 47,8mmHg IN, con una PIO máxima registrada de 88mmHg. El cambio mínimo de la PIO para el cuadrante ST fue de 51,9±17,3mmHg y de 46,4±16,0mmHg para los ojos derechos e izquierdos, respectivamente. El cambio medio de la PIO para el cuadrante IN fue de 45,3±22,7mmHg y 16,8±15,8mmHg para los ojos derechos e izquierdos, respectivamente. Conclusiones: La depresión escleral, realizada en un entorno clínico rutinario, produce fluctuaciones de la PIO y puede afectar a la perfusión ocular. Son necesarios estudios adicionales que determinen las consecuencias a largo plazo de la depresión escleral rutinaria (AU)

Change in intraocular pressure during scleral depression.

PURPOSE: Manometric studies have found that intraocular pressure (IOP) rises 116-350 mmHg during scleral depression in surgical settings. No information is available regarding the effect of scleral depression on IOP in routine clinical settings. The aim of this study is to quantify the change in IOP that occurs when scleral depression is performed on normal eyes in a routine clinical setting. METHODS: A total of 28 eyes from 28 normal subjects were included. Tono-Pen tonometry was performed while scleral depression was performed in each of the two quadrants: superotemporal (ST) and inferonasal (IN). A post-procedure IOP measurement was obtained following each scleral depression examination. Both ST and IN quadrants were tested on all eyes, with the quadrant tested first chosen at random (15 ST, 13 IN). RESULTS: The mean IOP during scleral depression was 65.3 mmHg ST and 47.8 mmHg IN, with a maximum recorded IOP of 88 mmHg. The mean change in IOP for the ST quadrant was 51.9 ± 17.3 mmHg and 46.4 ± 16.0 mmHg for the right and left eyes, respectively. The mean change in IOP for the IN quadrant was 45.3 ± 22.7 mmHg and 16.8 ± 15.8 mmHg for the right and left eyes, respectively. CONCLUSIONS: Scleral depression as performed in a routine office setting produces wide fluctuations in IOP and may impair ocular perfusion. Additional studies are needed to determine the long-term consequences of routine scleral depression.

The expanding clinical spectrum of torpedo maculopathy.

PURPOSE: Torpedo maculopathy is an idiopathic, congenital, oval-shaped region of chorioretinal hypopigmentation located temporal to the macula. Torpedo lesions are typically unilateral, occasionally harbor an intraretinal cleft, and may be associated with varying degrees of hyperpigmentation. Visual acuity is usually normal, but the lesion may produce a scotoma in the visual field. There are no known associated systemic or ocular abnormalities. Diagnosis is based upon recognition of its characteristic shape and location. Because of its nonprogressive and generally benign nature, no treatment is required. CASE REPORTS: Two cases of torpedo maculopathy associated with fundus excavation are presented. To the best of our knowledge, this is the first reported association of torpedo maculopathy with fundus excavation. In one case, the visual acuity remained unaffected and in the other case the visual acuity was reduced to 20/50. In both cases, optical coherence tomography clearly demonstrates the excavated nature of the torpedo lesions. In case 1, where the visual acuity was normal, the excavation is remote from the fovea but in case 2, where the visual acuity was 20/50, the excavation encroaches upon the fovea. In both cases, a scotoma corresponding to the excavated region could be demonstrated. CONCLUSIONS: Torpedo maculopathy is a usually benign condition associated with normal visual acuity and normal visual fields. Our cases demonstrate that torpedo maculopathy may be associated with excavation of the fundus and a corresponding scotoma in the visual field. Visual acuity may be compromised should the excavation encroach upon the central fovea. Knowledge of this previously unreported clinical manifestation of torpedo maculopathy may aid in advancing the understanding of this condition and the care of patients with the disorder.

Anti-neural antibody reactivity in patients with a history of Lyme borreliosis and persistent symptoms.

Some Lyme disease patients report debilitating chronic symptoms of pain, fatigue, and cognitive deficits despite recommended courses of antibiotic treatment. The mechanisms responsible for these symptoms, collectively referred to as post-Lyme disease syndrome (PLS) or chronic Lyme disease, remain unclear. We investigated the presence of immune system abnormalities in PLS by assessing the levels of antibodies to neural proteins in patients and controls. Serum samples from PLS patients, post-Lyme disease healthy individuals, patients with systemic lupus erythematosus, and normal healthy individuals were analyzed for anti-neural antibodies by immunoblotting and immunohistochemistry. Anti-neural antibody reactivity was found to be significantly higher in the PLS group than in the post-Lyme healthy (p<0.01) and normal healthy (p<0.01) groups. The observed heightened antibody reactivity in PLS patients could not be attributed solely to the presence of cross-reactive anti-borrelia antibodies, as the borrelial seronegative patients also exhibited elevated anti-neural antibody levels. Immunohistochemical analysis of PLS serum antibody activity demonstrated binding to cells in the central and peripheral nervous systems. The results provide evidence for the existence of a differential immune system response in PLS, offering new clues about the etiopathogenesis of the disease that may prove useful in devising more effective treatment strategies.