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Purpose: To report on the prospective evaluation of photorefractive keratectomy (PRK) in experienced ametropic naval aviators that led to the approval of refractive surgery for military pilots. Methods: This was the first study evaluating refractive surgery in naval aviators. Return to flight status after PRK and clinical outcomes and subjective and objective flight performance were evaluated. Results: A total of 785 U.S. naval aviators were enrolled in the study. Average preoperative refraction was −2.92 ± 1.73 diopters (D) (range: +5.25 to −9.13 D). By 6 months, 85.9% of eyes were within ±0.50 D and 96.4% were within ±1.00 D of emmetropia. 94.4% of eyes achieved 20/20 or better, 74.3% had 20/16 or better, and 45.2% had 20/12.5 or better uncorrected distance visual acuity (UDVA) at 6 months. A total of 78.5% of aviators met return-to-flight criteria by 4 weeks, 83.3% by 8 weeks, and 90.8% by 12 weeks following PRK. All aviators eventually returned to full flight status. Cumulative flight experience included logging more than 48,000 flight hours and 19,500 landings in the 6 months following PRK. Psychometric questionnaire results showed that 78% reported improved ability to detect other aircraft and 92% reported improved ability to land on an aircraft carrier (82% significantly improved) compared to wearing corrective lenses. No one felt their vision was worse in these dynamic environments. All aviators indicated they would undergo the procedure again and would recommend it to a fellow aviator. Conclusions: This prospective study in U.S. naval aviators determined PRK to be safe and effective in a unique patient population operating in a visually demanding and hazardous environment. The program continues to be enthusiastically supported by aviators and PRK is now allowed in all branches of the military and for National Aeronautics and Space Administration astronauts. [J Refract Surg. 2024;40(6):e371–e380.]

Purpose: To present the outcomes of the U.S. Navy photorefractive keratectomy (PRK) accessioning study conducted between 2000 and 2005 that helped lead to the acceptance of laser vision correction within the U.S. aviation industry. Methods: In this prospective masked study, a total of 301 students who had PRK and underwent naval flight training were compared to 4,368 untreated peers. Three training pipelines were compared: propeller/jet transport, jet fighters, and helicopters. The evaluated metrics were flight and academic performance (assessed for the primary and advanced stage of the training as normalized Navy Standard Score [NSS]), as well as the student attrition rate from training. Results: The attrition rate was lower in the PRK group compared to controls (15.9% vs 23.2%; P = .004). In the primary stage of training, students who had PRK outperformed controls in flight training performance in the propeller/jet transport pipeline (average NSS after PRK: 52.4 ± 7.5 vs controls: 50.7 ± 6.4, P = .02), but the flight performance in the jet fighter and helicopter pipelines was comparable between the two groups. Academic performance in the primary stage of training was approximately 7% to 13% higher in students who had PRK for all training pipelines. During the advanced training stage, there was no difference in the flight performance between the groups in any of the presented pipelines. Academic performance was significantly better for students who had PRK in the helicopter pipeline (51.2 ± 11.0 vs 46.7 ± 11.7 P < .001) but comparable between the two groups in the remaining pipelines. Conclusions: Refractive surgery did not have adverse effects on flight performance metrics. Pilots who had PRK had comparable or better outcomes than their untreated peers. [J Refract Surg. 2024:40(3):e173–e181.]

BACKGROUND AND OBJECTIVES: To evaluate the safety, tolerability, and biological activity of a topical selective integrin inhibitor (OTT166) eyedrop administered BID for diabetic retinopathy (DR) and diabetic macular edema (DME). STUDY DESIGN/MATERIALS AND METHODS: A prospective, multicenter, randomized, double-masked Phase 1b study. Subjects with nonproliferative DR and DME with central subfield thickness (CST) > 325 microns were randomized to OTT166 eyedrops (2.5% or 5%) BID for 28 days. Subjects were followed for an additional 28 days after treatment cessation. RESULTS: Forty-four subjects were enrolled. No drug-related serious adverse events (SAEs) and two drug-related adverse events (AEs) were reported. OTT166 was well-tolerated with no evidence of ocular toxicity. Best-corrected visual acuity (BCVA) remained stable. Mean central retinal thickness (CRT) overall was variable: +12.8/+1.8 microns at Day 28 (end of treatment) and −50.3/+5.5 microns at Day 56 (end of study) for the 2.5% and 5% groups, respectively. Median CRT overall demonstrated consistent reduction by end of study: −39.0/−16.5 microns for the 2.5% and 5% groups, respectively. Median responses were greater in the treatment-naïve group (−41.5/−26.0 microns for the 2.5% and 5% groups, respectively). Thirty-seven percent of ‘responder’ subjects exhibited a mean reduction in CRT of 46.6 microns on optical coherence tomography (OCT) at end of treatment (Day 28) which persisted to end of the study (Day 56) – mean reduction of 67.4 microns, suggesting a durable effect. CONCLUSION: OTT166 eyedrops were safe, well-tolerated, and demonstrated biological activity in 37% of responders. These results warrant further evaluation of OTT166 eyedrops. [Ophthalmic Surg Lasers Imaging Retina 2022;53:553–560.]

Purpose: To compare the Visian Toric Implantable Collamer Lens (TICL), a toric phakic intraocular lens (IOL), and photorefractive keratectomy (PRK) in the correction of moderate to high myopic astigmatism. Methods: This prospective, randomized study consisted of 43 eyes implanted with the TICL (20 bilateral cases) and 45 eyes receiving PRK with mitomycin C (22 bilateral cases) with moderate to high myopia (−6.00 to −20.00 diopters [D] sphere) measured at the spectacle plane and 1.00 to 4.00 D of astigmatism. All patient treatment and follow-up occurred at the Naval Medical Center San Diego. Study follow-up was 1 day, 1 week, 1, 3, 6, and 12 months postoperative. Results: Mean best spectacle-corrected visual acuity (BSCVA), change in BSCVA, proportion of cases with improvement of 1 or more lines of BSCVA, proportion of cases with BSCVA and uncorrected visual acuity (UCVA) 20/12.5 or better, proportion of cases with BSCVA and UCVA 20/16 or better (6 months, 88% vs 54%, P=.002), and predictability ±1.00 D (6 months, 100% vs 67%, P<.001) were all significantly better in the TICL group than the PRK group at all time periods studied postoperatively. Similarly, contrast sensitivity, tested at both the 5% photopic level and the 25% mesopic level, was significantly better at all postoperative time points in the TICL group. Mean spherical equivalent refraction was closer to emmetropia (0.28±0.41 vs 0.76±0.86, P=.005), and predictability ±0.50 D and stability of manifest refraction (±0.50 D and ±1.00 D) were significantly better in the TICL group at all postoperative visits through 6 months. Mean astigmatism correction at 6 months was not significantly different between the two groups (0.52±0.33 vs 0.46±0.35, P=.450). Conclusions: The TICL performed better than PRK in all measures of safety (BSCVA), efficacy (UCVA), predictability, and stability in this comparison, supporting the TICL as a viable alternative to existing refractive surgical treatments. [J Refract Surg. 2007;23:853–867.]

Background: Clozapine is the most effective medication for treatment–refractory schizophrenia but is associated with significant adverse drug effects, including hypotension and dizziness, which have a negative impact on quality of life and treatment compliance. Available evidence for the management of clozapine-induced hypotension is scant. Objectives: Due to limited guidance on the safety and efficacy of pharmacological treatments for clozapine-induced hypotension, we set out to systematically review and assess the evidence for the management of clozapine-induced hypotension and provide guidance to clinicians, patients, and carers. Design: We undertook a systematic review of the safety and efficacy of interventions for clozapine-induced hypotension given the limited available evidence. Data Sources and Methods: PubMed, Embase, PsycINFO, CINAHL, and the Cochrane trial Registry were searched from inception to November 2021 for literature on the treatment strategies for clozapine-induced hypotension and dizziness using a PROSPERO pre-registered search strategy. For orthostatic hypotension, we developed a management framework to assist in the choice of intervention. Results: We identified nine case studies and four case series describing interventions in 15 patients. Hypotension interventions included temporary clozapine dose reduction, non-pharmacological treatments, and pharmacological treatments. Midodrine, fludrocortisone, moclobemide and Bovril® combination, and etilefrine were associated with improvement in symptoms or reduction in orthostatic hypotension. Angiotensin II, arginine vasopressin, and noradrenaline successfully restored and maintained mean arterial pressure in critical care situations. A paradoxical reaction of severe hypotension was reported with adrenaline use. Conclusion: Orthostatic hypotension is a common side effect during clozapine titration. Following an assessment of the titration schedule, salt and fluid intake, and review of hypertensive and nonselective α1-adrenergic agents, first-line treatment should be a temporary reduction in clozapine dose or non-pharmacological interventions. If orthostatic hypotension persists, fludrocortisone should be trialled with monitoring of potassium levels and sodium and fluid intake. Midodrine may be considered second-line or where fludrocortisone is contraindicated or poorly tolerated. For patients on clozapine with hypotension in critical care settings, the use of adrenaline to maintain mean arterial pressure should be avoided. Registration: PROSPERO (Registration No. CRD42020191530)

Background: A prolonged electrocardiogram (ECG) QT interval is associated with cardiac events and increased mortality. Antipsychotics can prolong the QT interval. The QT interval requires correction (QTc) for heart rate using a formula or QT-nomogram. The QT and QTc can be calculated automatically by the ECG machine or manually; however, machine-measured QT(c) intervals may be inaccurate. Objective: We aimed to investigate the mean QTc and proportion of prolonged QTc intervals in people taking antipsychotic medicines. Methods: We conducted an observational retrospective chart review and data analysis of all consecutive patients taking antipsychotics, with an ECG record, admitted to the psychiatric unit of a large tertiary hospital in Brisbane, Australia, between 1 January 2017 and 30 January 2019. We investigated the mean QTc of people taking antipsychotics to determine differences using (a) machine versus manual QT interval measurement and (b) QTc correction formulae (Bazett, Fridericia, Framingham, Hodges and Rautaharju) and the QT-nomogram. We also determined the number of people with a prolonged QTc using different methods and compared rates of prolonged QTc with antipsychotic monotherapy and polypharmacy. Results: Of 920 included people, the mean (±SD) machine-measured, Bazett-corrected QT interval (recorded from the ECG) was 435 ms (±27), significantly longer (p < 0.001) than the mean manually measured corrected QT intervals with Fridericia 394 ms (±24), Framingham 395 ms (±22), Hodges 398 ms (±22) and Rautaharju 400 ms (±24) formulae. There were significantly more people with a prolonged QTc using machine-measured QT and the Bazett formula (12.0%, 110/920) when compared with manually measured QT and the Fridericia formula (2.2%, 20/920) or QT-nomogram (0.7%, 6/920). Rates of QTc prolongation did not differ between people taking antipsychotic polypharmacy compared with monotherapy. Conclusion: Machine-measured QTc using the Bazett formula overestimates the QTc interval length and number of people with a prolonged QTc, compared with other formulae and the QT-nomogram. We recommend manually measuring the QT and correcting with the Fridericia formula or QT-nomogram prior to modifying antipsychotic therapies.

The authors report a case of an immunocompetent 38-year-old male who presented with an indolent keratitis that eluded diagnosis after multiple cultures taken over 9 months. He was started initially on medications against Acanthamoeba, after presenting with a nearly complete corneal ring 2 months after trauma. These medications likely partially treated his condition, thereby making laboratory diagnosis more difficult. He was identified as having Encephalitozoon hellum by PCR. The patient subsequently underwent cornea transplant after a full course of medical treatment and recovered best-corrected visual acuity of 20/20.

Laser in situ keratomileusis (LASIK) has become the community standard in corneal refractive surgery and is being performed by surgeons in the Army, Navy, and Air Force. LASIK differs from photorefractive keratectomy (PRK) in that a partial-thickness corneal flap is created in the LASIK procedure before removing a microscopic amount of corneal tissue, whereas no flap creation is required in PRK. The benefits of LASIK include minimal discomfort after surgery, as well as a much faster return of visual function. PRK involves a surface ablation and therefore heals differently, involving more discomfort and a slower return of functional vision. LASIK flap integrity is a concern to anyone undergoing the procedure, as well as for those making recommendations on the best form of refractive surgery for military personnel. A case report and a review of the literature are presented on the identification and management of LASIK flap trauma.