Comparison of Simulation-Based versus Cadaveric-Tissue-Based Ocular Trauma Training on Novice Ophthalmologists: Repair of Corneal Laceration Model.

Purpose The aim of this study was to evaluate whether the simulated tissue models may be used in place of animal-based model for corneal laceration repair for surgical skills acquisition. Design Prospective randomized controlled trial. Participants Seventy-nine military and civilian 2nd- and 3rd-year ophthalmology residents and 16 staff ophthalmologists participating in the Tri-Service Ocular Trauma Skills Laboratory at the Uniformed Services University (Bethesda, MD). Methods Resident ophthalmologists underwent preliminary evaluation of their ability to close a 5-mm linear, full-thickness corneal laceration involving the visual axis. They then were randomized to undergo 90 to 120 minutes of either simulator-based (SIM) or swine cadaveric-tissue-based (CADAVER) corneal laceration repair. The same evaluation was performed post training. On a more limited basis, the study was repeated for attending ophthalmologists to act as a pilot for future analysis and test efficacy for "refresher" training. Main Outcome Measures Successful wound closure with secondary outcomes of suture length, tension, depth, and orientation, as graded by attending ophthalmologists. Results No significant difference in CADAVER versus SIM groups in the primary outcome of watertight wound closure of the corneal laceration. CADAVER group performed better than SIM group for certain metrics (suture depth, p = 0.009; length, p = 0.003; and tension, p = 0.043) that are associated with poor wound closure and increased amount of induced corneal astigmatism. For attending ophthalmologists, six of the eight in each group (SIM and CADAVER) retained or improved their skills. Conclusions For resident ophthalmologists, SIM training is sufficient for achieving the primary outcome of watertight wound closure. However, CADAVER training is superior for wound metrics for the ideal closure. For attending ophthalmologists, SIM training may be useful for retention of skills.

Contrast Sensitivity After Wavefront-Guided and Wavefront-Optimized PRK and LASIK for Myopia and Myopic Astigmatism.

PURPOSE: To compare contrast sensitivity among participants undergoing wavefront-guided or wavefront-optimized photorefractive keratectomy (PRK) or LASIK for the treatment of myopia or myopic astigmatism 12 months after surgery. METHODS: In a prospective, randomized clinical trial, 215 participants with myopia ranging from -0.50 to -7.25 diopters (D) and less than -3.50 D of manifest astigmatism electing to undergo either LASIK or PRK were randomized to receive wavefront-guided or wavefront-optimized treatment. Corrected Super Vision Test (Precision Vision, La Salle, IL) high contrast and small letter contrast sensitivity, uncorrected postoperative contrast sensitivity function, and uncorrected and corrected distance visual acuity were measured preoperatively and at 1, 3, 6, and 12 months postoperatively. RESULTS: There was a significant difference within each of the four groups over time when measuring high contrast visual acuity (P < .001) and small letter contrast sensitivity (P < .001), with the most significant decrease occurring 1 month postoperatively. However, there were no significant differences when comparing the four groups for high contrast sensitivity (P = .22) or small letter contrast sensitivity (P = .06). The area under the logarithm of contrast sensitivity function did not differ significantly over time (P = .09) or between groups (P = .16). A pairwise comparison of preoperative to 12-month CDVA showed a significant improvement in all groups (P < .017). The change in CDVA was also significantly different between groups as determined by one-way analysis of variance (P = .003). CONCLUSIONS: Wavefront-guided and wavefront-optimized PRK and LASIK procedures maintained high contrast, small letter contrast sensitivity, and contrast sensitivity function 12 months postoperatively. Although the recovery period for visual performance was longer for PRK versus LASIK, there was no significant difference in treatment type or treatment profile at 12 months postoperatively. [J Refract Surg. 2018;34(9):590-596.].

Wavefront-Guided Versus Wavefront-Optimized Photorefractive Keratectomy: Visual and Military Task Performance.

PURPOSE: To compare visual performance, marksmanship performance, and threshold target identification following wavefront-guided (WFG) versus wavefront-optimized (WFO) photorefractive keratectomy (PRK). METHODS: In this prospective, randomized clinical trial, active duty U.S. military Soldiers, age 21 or over, electing to undergo PRK were randomized to undergo WFG (n = 27) or WFO (n = 27) PRK for myopia or myopic astigmatism. Binocular visual performance was assessed preoperatively and 1, 3, and 6 months postoperatively: Super Vision Test high contrast, Super Vision Test contrast sensitivity (CS), and 25% contrast acuity with night vision goggle filter. CS function was generated testing at five spatial frequencies. Marksmanship performance in low light conditions was evaluated in a firing tunnel. Target detection and identification performance was tested for probability of identification of varying target sets and probability of detection of humans in cluttered environments. RESULTS: Visual performance, CS function, marksmanship, and threshold target identification demonstrated no statistically significant differences over time between the two treatments. Exploratory regression analysis of firing range tasks at 6 months showed no significant differences or correlations between procedures. Regression analysis of vehicle and handheld probability of identification showed a significant association with pretreatment performance. CONCLUSIONS: Both WFG and WFO PRK results translate to excellent and comparable visual and military performance.

Wavefront-guided versus wavefront-optimized photorefractive keratectomy: Clinical outcomes and patient satisfaction.

PURPOSE: To compare visual outcomes following Visx Star S4 Customvue wavefront-guided and Allegretto Wave Eye-Q 400 Hz wavefront-optimized photorefractive keratectomy (PRK). SETTING: Warfighter Refractive Eye Surgery Program and Research Center, Fort Belvoir, Virginia, and Walter Reed National Military Medical Center, Bethesda, Maryland, USA. DESIGN: Prospective randomized clinical trial. METHODS: Active-duty United States military soldiers were randomized to have wavefront-guided (Visx Star S4 Customvue) or wavefront-optimized PRK. Participants were followed up to 12 months postoperatively. Primary outcome measures were uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and manifest spherical equivalent (SE). Secondary outcome measures included refractive astigmatism, higher-order aberrations (HOAs), contrast sensitivity, subjective visual complaints, and patient satisfaction. RESULTS: The study evaluated 108 soldiers (mean age 30.3 years ± 6.3 [SD]; mean manifest SE -3.51 ± 1.63 D). At 12 months postoperatively, achieved UDVA, CDVA, manifest SE, and refractive astigmatism were comparable between wavefront-guided and wavefront-optimized groups (P > .213). Spherical aberration and total HOAs significantly increased from baseline in both groups (P < .006). The change in coma, trefoil, spherical aberration, and total HOAs (P > .254) were comparable between groups. There were fewer losses of photopic low-contrast visual acuity (LCVA) at 5% contrast after wavefront-guided compared to wavefront-optimized treatment (P = .003). There was no significant difference between treatment groups in visual symptoms, overall vision expectation, and satisfaction (P > .075). CONCLUSION: Wavefront-guided treatment offered a small advantage in photopic LCVA. Refractive outcomes, HOAs, self-reported visual difficulties, overall vision expectation, and satisfaction were otherwise comparable between wavefront-guided and wavefront-optimized treatments. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Flap-off epi-LASIK versus automated epithelial brush in PRK: a prospective comparison study of pain and reepithelialization times.

PURPOSE: To compare the effect of flap-off epi-LASIK versus automated brush epithelial removal on pain and wound healing in low myopic photorefractive keratectomy (PRK). METHODS: In this prospective intraindividual study 60 patients received surface ablation in each eye. Epithelial removal was performed by an automated brush technique in one eye (brush group) and epi-LASIK with flap removal (flap-off group) in the fellow eye. The epithelial defect size was measured daily after surgery until both eyes were reepithelialized. Postoperative pain on a scale from 0 to 6 and topical and oral analgesic medication use was recorded until the bandage contact lens was removed. RESULTS: The flap-off group had significantly less postoperative pain on days 1 (P=.0003), 2 (P=.0001), 3 (P<.0001), and 4 (P<.0001) compared to the brush group. However, the average difference in pain scores between groups was only 0.33 points out of 6. No difference was noted in the normalized overall percentage rate of healing over the first 4 days in the flap-off group (5.41±1.39%/hour) compared to the brush group (5.42±1.94%/hour) (P=.97). CONCLUSIONS: The flap-off group showed a statistically but not clinically significant advantage over the brush group in pain scores. However, no difference was noted in the percentage rate of epithelial healing time between the two groups.

Blast eye injuries: a review for first responders.

As the rate of terrorism increases, it is important for health care providers to become familiar with the management of injuries inflicted by blasts and explosions. This article reviews the ocular injuries associated with explosive blasts, providing basic concepts with which to approach the blast-injured patient with eye trauma. We conducted a literature review of relevant articles indexed in PubMed between 1948 and 2007. Two hundred forty-four articles were reviewed. We concluded that ocular injury is a frequent cause of morbidity in blast victims, occurring in up to 28% of blast survivors. Secondary blast injuries, resulting from flying fragments and debris, cause the majority of eye injuries among blast victims. The most common blast eye injuries include corneal abrasions and foreign bodies, eyelid lacerations, open globe injuries, and intraocular foreign bodies. Injuries to the periorbital area can be a source of significant morbidity, and ocular blast injuries have the potential to result in severe vision loss.

Oral gabapentin for the treatment of postoperative pain after photorefractive keratectomy.

PURPOSE: To evaluate oral gabapentin for postoperative pain after photorefractive keratectomy (PRK). DESIGN: Prospective, nonrandomized clinical trial. METHODS: In additional to a standard regimen of topical antibiotics, topical steroids, and topical tetracaine as required, all PRK patients at our laser vision center were treated after surgery for pain for a two-month period with Percocet (oxycodone/acetaminophen) [Endo Pharmaceuticals; Chadds Ford, Pennsylvania, USA] 5 mg/325 mg as required for three days (control group). Patients completed a pain assessment survey using a faces pain scale (from zero through 6) on the evening of surgery and each subsequent morning and evening until postoperative day 3. A successive cohort of patients received Neurontin (gabapentin) [Pfizer, New York, New York, USA] 300 mg thrice daily (first dose administered two hours or more before the procedure) as an oral pain medication for three days, and the same survey data were collected. RESULTS: Data were collected on 141 patients in each cohort. Successful pain management score (defined as faces zero through 2 on the scale) differences did not reach statistical significance between the two cohorts except on the morning of the second postoperative day, when gabapentin was superior. On all postoperative days, patients in the oxycodone/acetaminophen cohort used significantly less tetracaine eye drops as required. The percent of patients rating overall pain experience as better than expected was 35% and 36%, those rating pain experience as about what was expected was 50% and 49%, and those rating pain experience as worse than expected was 15% and 15% in the oxycodone/acetaminophen and gabapentin cohorts, respectively. CONCLUSIONS: We found no difference in overall subjective pain management ratings between gabapentin and oxycodone/acetaminophen for postoperative PRK pain, although gabapentin was associated with significantly more frequent use of anesthetic eye drops as required.

Estradiol enhances long term potentiation in hippocampal slices from aged apoE4-TR mice.

Hormone replacement therapy to treat or prevent Alzheimer Disease (AD) in postmenopausal women is controversial because it may pose other health risks such as cancer and thromboembolism. ApoE status is thought to influence the nootropic efficacy of hormone therapy, but findings are neither consistent nor well understood. We used a known in vitro memory model (long-term potentiation, LTP) in aged (24-27 month) female targeted replacement mice expressing human apoE3 or E4 to compare the effects of exogenous estradiol. Recording medial perforant path evoked field potentials in dentate gyrus of hippocampal slices, we found that both strains exhibited comparable basal synaptic transmission as assessed by input/output functions and paired pulse depression, and that these measures were not affected by estradiol. Vehicle-treated groups from both strains showed comparable LTP. Estradiol had no effect on LTP in apoE3-TR, but selectively increased LTP magnitude in apoE4-TR. The estradiol induced enhancement of LTP in aged female apoE4-TR is consistent with recent clinical observations that estrogen replacement decreases AD risk in some women with apoE4. Elucidating the mechanism of this selective enhancement may lead to more informed treatment decisions as well as to the development of safer alternatives to hormone therapy.

Amyloid-beta1-42 reduces neuronal excitability in mouse dentate gyrus.

Amyloid-beta (Abeta) is causally implicated in Alzheimer's disease and neuroplasticity failure has acquired validity as a possible mechanism of early AD pathogenesis. We have previously demonstrated that oligomeric Abeta(1-42) inhibits LTP in the dentate gyrus of rat hippocampal slices. We now show, using whole cell recordings in hippocampal granule cells, that oligomeric Abeta(1-42) decreases neuronal excitability. In particular, Abeta(1-42) application was associated with a decrease in the number of action potentials fired in response to current injection, and with an increase in the amplitude of the afterhyperpolarization. Reduced excitability may underlie the Abeta-mediated impairment in neuroplasticity, and ultimately may contribute to the memory loss in Alzheimer disease.

Infectious keratitis after photorefractive keratectomy in the United States army and navy.

PURPOSE: To review the incidence, culture results, clinical course, management, and visual outcomes of infectious keratitis after photorefractive keratectomy (PRK) at 6 Army and Navy refractive surgery centers. DESIGN: Retrospective study. PARTICIPANTS: Twelve thousand six hundred sixty-eight Navy and Army sailors and service members. METHODS: Army and Navy refractive surgery data banks were searched for cases of infectious keratitis. A retrospective chart review and query of the surgeons involved in the care of those patients thus identified provided data regarding preoperative preparation, perioperative medications, treatment, culture results, clinical course, and final visual acuity. RESULTS: Between January 1995 and May 2004, we performed a total of 25337 PRK procedures at the 6 institutions. Culture proven or clinically suspected infectious keratitis developed in 5 eyes of 5 patients. All patients received topical antibiotics perioperatively. All cases presented 2 to 7 days postoperatively. Cultures from 4 cases grew Staphylococcus, including 2 methicillin-resistant S. aureus (MRSA). One case of presumed infectious keratitis was culture negative. There were no reported cases of mycobacterial or fungal keratitis. In addition, we identified 26 eyes with corneal infiltrates in the first postoperative week that were felt to be sterile, and which resolved upon removal of the bandage contact lens and increasing antibiotic coverage. CONCLUSIONS: Infectious keratitis is a rare but potentially vision-threatening complication after PRK. It is often caused by gram-positive organisms, including MRSA. Early diagnosis, appropriate laboratory testing, and aggressive antimicrobial therapy can result in good outcomes.

Blockade of nicotinic acetylcholine receptors suppresses hippocampal long-term potentiation in wild-type but not ApoE4 targeted replacement mice.

Both impaired nicotinic neurotransmission and the inheritance of apoE4 are associated with increased risk for Alzheimer disease (AD) as well as other deficiencies in memory-related behavior. Long-term potentiation (LTP), a cellular model of memory, is known to be altered by nicotinic agents. Recent studies also support an emergent role for apoE in LTP. We compared the effects of mecamylamine, a nonspecific antagonist of nicotinic acetylcholine receptors (nAChRs), on basal synaptic transmission and LTP in hippocampal slices from wild-type (wt) mice and targeted replacement mice expressing human apoE4 (apoE4-TR). Field excitatory postsynaptic potentials (EPSPs) were recorded in the dentate gyrus (DG) in response to medial perforant path activation, and theta burst stimulation was used to induce LTP. Bath application of mecamylamine (3 microM) did not alter input-output relationships or paired pulse depression in either mouse strain. Under control conditions, apoE4-TR mice showed significantly less LTP than wt mice (17.5% +/- 3.2%, n = 9, vs. 30.1% +/- 3.9%, n = 11, P < 0.02). Mecamylamine reduced LTP in wt mice to a level that was similar to control levels for apoE4-TR mice (15.7% +/- 3.4%, n = 9), whereas apoE4-TR showed no further reduction of LTP (16.6% +/- 3.7%, n = 8) by mecamylamine. Thus mice expressing human apoE4 differ from wt mice both in their capacity for LTP and in the effect on LTP of nicotinic cholinergic blockade. It is possible that nicotinic neurotransmission is already compromised in apoE4-TR mice and, hence, that interference with the integrity of this cholinergic system represents a mechanism by which inheritance of the apoE4 allele contributes to cognitive risk.

Delayed-onset expulsive choroidal hemorrhage attributed to an acute elevation in systemic blood pressure following traumatic globe rupture.

The authors describe a 78-year-old woman who suffered a traumatic partial dehiscence of a penetrating keratoplasty on the day prior to presentation. While awaiting surgical repair, the patient experienced an expulsive choroidal hemorrhage necessitating a primary evisceration of the eye. This case is unique because the hemorrhage can be largely attributed to the acute dramatic rise in systemic blood pressure that immediately preceded it. Management considerations for patients with open-globe injuries who have poorly controlled systemic hypertension should include close monitoring of vital signs in a controlled setting, anxiolysis, aggressive intervention for hypertensive lability, and hastening of surgical repair regardless of nothing by mouth status.

AMPA and NMDA receptor-mediated currents in developing dentate gyrus granule cells.

Granule cells (GCs) of the hippocampal dentate gyrus (DG) undergo postnatal neurogenesis such that cells at different maturational stages can be studied within an anatomically restricted region and a narrow animal age epoch. Using whole cell patch clamp recordings in hippocampal slices, we have previously found that input resistance (IR) correlates inversely with morphometric indicators of GC maturity. Using IR as an index of maturity we measured developmental changes in synaptic currents mediated by N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in GCs from 5- to 12-day rats. Peak NMDA and AMPA EPSC amplitudes increased, and the NMDA/AMPA ratio reversed with advancing cell age. NMDA EPSCs showed a maturational decrease in rise time but no change in decay time, whereas AMPA EPSCs showed neither rise nor decay time changes with development. Ifenprodil, a high affinity selective inhibitor of NR1/NR2B diheteromeric NMDA receptors, blocked approximately 50% of the peak amplitude of evoked NMDA EPSCs in all tested GCs regardless of their maturity and did not affect the measured kinetic properties. These data suggest that development of glutamatergic synapses follows distinct schedules. AMPA receptors possessed mature kinetics and became the dominant glutamatergic current within the age epoch studied, whereas NMDA receptors showed maturational changes in rise times but not decay kinetics. The reported modifications of EPSC properties are consistent with changes in receptor and synapse number, and relative quantities of AMPA and NMDA receptors. Changes in the subunit composition that determines NMDA decay kinetics may occur beyond the early neonatal period.

ApoE isoform-specific effects on LTP: blockade by oligomeric amyloid-beta1-42.

Amyloid-beta1-42 (Abeta1-42) is crucial to Alzheimer disease (AD) pathogenesis but the conformation of the toxic Abeta species remains uncertain. AD risk is increased by apolipoprotein E4 (apoE4) and decreased by apoE2 compared with the apoE3 isoform, but whether inheritance of apoE4 represents a gain of negative or a loss of protective function is also unresolved. Using hippocampal slices from apoE knockout (apoE-KO) and human apoE2, E3, and E4 targeted replacement (apoE-TR) mice, we found that oligomeric Abeta1-42 inhibited long-term potentiation (LTP) with a hierarchy of susceptibility mirroring clinical AD risk (apoE4-TR > apoE3-TR = apoE-KO > apoE2-TR), and that comparable doses of unaggregated Abeta1-42 did not affect LTP. These data provide a novel link among apoE isoform, Abeta1-42, and a functional cellular model of memory. In this model, apoE4 confers a gain of negative function synergistic with Abeta1-42, apoE2 is protective, and the apoE-Abeta interaction is specific to oligomeric Abeta1-42.

ApoE isoform affects LTP in human targeted replacement mice.

Inheritance of the epsilon4 allele for apolipoprotein E (apoE) increases the risk of Alzheimer disease and memory impairment, whereas epsilon2 decreases these risks compared with the most common epsilon3 allele, but the mechanism for these effects is unknown. Long-term potentiation (LTP) is an experimentally induced increase in synaptic efficacy that models memory. Using hippocampal slices from wild type (WT), apoE knockout (apoE-KO), and targeted replacement mice expressing human apoE2, E3, or E4 (apoE-TR) we found that although all strains had comparable basal synaptic transmission, LTP was significantly greater in WT and apoE3-TR than in apoE-KO, apoE2-TR or apoE4-TR. This novel system may be used to investigate the mechanisms of apoE isoform dependent modulation of susceptibility to memory impairment.

Soluble oligomers of beta amyloid (1-42) inhibit long-term potentiation but not long-term depression in rat dentate gyrus.

The dementia in Alzheimer disease (AD) is usually attributed to widespread neuronal loss in conjunction with the pathologic hallmarks of intracellular neurofibrillary tangles and extracellular plaques containing amyloid (A beta) in fibrillar form. Recently it has been demonstrated that non-fibrillar assemblies of A beta possess electrophysiologic activity, with the corollary that they may produce dementia by disrupting neuronal signaling prior to cell death. We therefore examined the effects of soluble oligomers of A beta(1-42) on long-term potentiation (LTP) and long-term depression (LTD), two cellular models of memory, in the dentate gyrus of rat hippocampal slices. Compared with vehicle controls, slices pre-incubated 60 min in the presence of A beta-derived diffusible ligands (ADDLs) showed no differences in threshold intensity to evoke a synaptic response, slope of field excitatory post-synaptic potentials (EPSPs), or the input/output function. Tetanus-induced LTP and reversal of LTD were strongly inhibited in ADDLs-treated slices whereas LTD was unaffected. These data suggest that soluble non-fibrillar amyloid may contribute to the pathogenesis of AD both by impairing LTP/memory formation at the cellular level and by creating 'neuroplasticity imbalance' manifested by unopposed LTD in the setting of impaired capacity for neural repair via reversal of LTD or LTP.