What Happens 20 to 30 years After Radial Keratotomy? Case Series.

ABSTRACT: Radial keratotomy (RK) was commonly performed in the 1980s and 1990s. We aimed to clarify the current status of post-RK refractive correction and treatment. We retrospectively reviewed the charts of 70 patients with a history of RK. Of the 70 patients, 44 were identified for clinical outcomes. Refractive or therapeutic intervention (rigid gas-permeable contact lens fit, spectacle prescription, corneal surgery, and use of pilocarpine hydrochloride for photophobia) was possible in 59% of patients with postoperative visual deterioration after RK; in the remaining 41%, therapeutic intervention was not possible. Rigid gas-permeable contact lens fit for corneal irregular astigmatism was the most common refractive intervention and was effective in 36% of cases in the university hospital.

Association of Treatment Duration and Clinical Outcomes in Dry Eye Treatment with Sutureless Cryopreserved Amniotic Membrane.

Background: While sutureless, cryopreserved amniotic membrane (cAM) has been shown to significantly improve signs and symptoms of dry eye disease (DED), no studies have assessed the association of cAM treatment duration to the differential response in clinical outcomes. Methods: A multi-center, retrospective study was conducted on patients with moderate-to-severe DED who were treated with self-retained cAM (Prokera® Slim) for 2 to 7 days. The primary outcome measure was DEWS severity score assessed at 1 week, 1 month, and 3 months. Secondary outcome measures included ocular discomfort, visual symptoms, corneal staining, and visual acuity. Results: A total of 89 eyes (77 patients) with moderate-to-severe DED (DEWS severity 3.24 ± 0.56) received treatment with self-retained cAM for 2 days (n = 10), 3 days (n = 15), 4 days (n = 12), 5 days (n = 19), 6 days (n = 6), or 7 days (n = 27). DEWS scores significantly improved at 1 week, 1 month, and 3 months for all treatment duration groups, with no significant difference observed between groups at any timepoint. In addition to an improvement in DEWS severity scores, those receiving cAM treatment for 2 days demonstrated a significant improvement in corneal staining, visual symptoms, and ocular discomfort at 1 week, 1 month, and 3 months. Conclusion: This retrospective study suggests that a single placement of self-retained cAM for 2 days can significantly improve signs and symptoms of DED with a lasting benefit observed for up to 3 months.

Identifying behaviors that characterize emergence delirium: An observational study.

BACKGROUND: Diagnostic criteria for emergence agitation are sensitive but not specific; they misclassify patients who are angry or upset as having emergence delirium. AIMS: The aim of this three-phase study was to determine expert agreement on the behaviors that differentiate children with emergence delirium from those without. METHODS: In the first phase of this observational study, pediatric dental patients were video recorded while awakening from anesthesia. In the second phase, salient 10 s segments of the recordings showing patient activity were shown to an expert audience of pediatric dentists, anesthesiologists and Post Anesthetic Care nurses, who scored the recordings as showing or not showing "true emergence delirium." In phase 3, the video segments were assessed by three research assistants using a behavior checklist for features that discriminate between those scored "true emergence delirium" and those scored "NOT true emergence delirium" by the experts. RESULTS: One hundred and fifty-four pediatric dental patients were included. Subsequently, an expert audience consisting of 10 anesthesiologists, 12 anesthesiology residents, 3 pediatric dentists, and 4 experienced Post Anesthesia Care Unit nurses rated each 10-second video segment. This resulted in three groups of patients: a group for whom all experts agreed was "True emergence delirium" (n = 33; CI 21 to 45), a group for whom all agreed was "Not True emergence delirium" (n = 120; CI 107 to 133), and a group where experts disagreed (n = 11; CI 4 to 18). Three research assistants then completed a behavior checklist for each of the 33 "True emergence delirium" video segments and matched "Not True" controls. Twenty-four behaviors were identified as significantly different between videos scored True emergence delirium and those scored Not True emergence delirium. Research assistants reached almost perfect agreement (0.81-1.00) on one behavior, and substantial agreement (0.61-0.80) on seven behaviors that characterized "True emergence delirium." CONCLUSIONS: Eight behaviors that differentiate pediatric dental patients with emergence delirium from those without were found. These discriminators may be used to develop a scale that will lead to better diagnosis and treatment of emergence delirium.

A randomized phase 2 clinical trial of phentolamine mesylate eye drops in patients with severe night vision disturbances.

PURPOSE: Dim light vision disturbances (DLD) comprise a wide range of symptoms affecting the quality of vision at low illumination including glare, halos, and starbursts. This exploratory study investigated 1.0% phentolamine mesylate ophthalmic solution (PMOS) as a treatment to improve vision and image quality for patients with DLD. METHODS: In this placebo-controlled, randomized, double-masked clinical trial, 24 adult patients with severe DLD were randomized in a 2:1 ratio to receive either one dose of PMOS or placebo. Subjects were eligible if they reported experiencing severe night vision difficulty that was not eliminated by distance spectacle correction and scored ≥0.3 log units below the normal range of contrast sensitivity assessed under mesopic conditions with glare at ≥2 spatial frequencies. Key efficacy outcomes were change from baseline in pupil diameter, contrast sensitivity, and visual acuity. Safety measures including intraocular pressure, conjunctival hyperemia, and systemic effects were also assessed. RESULTS: Eight subjects were randomized to placebo (63% female; mean age 47 years) and 16 were randomized to PMOS (75% female; mean age 42 years). Mean (SD) pupil diameter of PMOS-treated subjects decreased significantly - 1.3 mm (0 to - 2.8 mm) with p < 0.0001. Mean contrast sensitivity with glare in PMOS-treated subjects improved significantly post-treatment at spatial frequencies 3, 6, 12, and 18 cycles per degree (p ≤ 0.03). PMOS also demonstrated improvements in the numbers of letters read for mesopic and photopic, high- and low-contrast visual acuity (LCVA). Importantly, a statistically greater proportion of PMOS-treated eyes registered mesopic LCVA 5 letter (69% vs. 31%, p = 0.029) and 10 letter (34% vs. 6%, p = 0.04) improvement, with a trend at 15 letters (19% vs. 0%, p = 0.16). PMOS was well tolerated with the only reported side effect being a mild increase in conjunctival hyperemia. CONCLUSION: PMOS was well tolerated and effectively reduced pupil size with improvements in contrast sensitivity and visual acuity in adults with severe DLD. Future Phase 3 studies should be conducted to further evaluate its potential to treat DLD. TRIAL REGISTRATION: The trial registration number is NCT04004507 (02/07/2019). Retrospectively registered.

Classification of Presbyopia by Severity.

There are close to two billion individuals globally living with presbyopia. In spite of its ubiquitous and progressive nature, there is no widely accepted, formal guideline or consensus statement on the classification of presbyopia by degree of severity. A panel of leading eye care professionals representing both optometrists and ophthalmologists convened virtually to discuss and document their combined assessments from the body of literature and clinical practice expertise in this commentary. In light of emerging therapies, classifying presbyopia by mild, moderate, or advanced severity may help provide consistency of diagnosis among eye care providers and may aid in managing patient expectations with different treatment options.

Advances in Corneal Surgical and Pharmacological Approaches to the Treatment of Presbyopia.

The purpose of this article is to review the current status of presbyopia amelioration with surgical and pharmacologic procedures that partially compensate for loss of accommodation in advance of cataract surgery and lens replacement. Over the last few years, several corneal surgical and topical pharmacological approaches for the treatment of presbyopia have been introduced to the marketplace or are in the developmental pipeline. The approaches vary in invasiveness, duration of effect, reversibility, risk/benefit ratio, and clinical results. The advantages and disadvantages for each are discussed. Corneal surgical interventions aim to provide improved near and intermediate vision in patients with presbyopia through refractive means that extend ocular depth of focus through shape modification. The use of miotic drops or corneal lamellar implants extend depth of focus with the "pinhole" aperture size reduction effect. Unlike in adults younger than 40 years, the refractive status of the patient with presbyopia is not stable. Hence, procedures that provide a permanent refractive change may not provide long-term full correction; eye drops or other treatments that are self-reversing in time or are easily reversible may be used as needed. On the horizon, procedures are being explored that may add years of functional lens accommodation by preserving the deformable gel properties of the lens. [J Refract Surg. 2021;37(6 Suppl):S20-S27.].

Phentolamine Eye Drops Reverse Pharmacologically Induced Mydriasis in a Randomized Phase 2b Trial.

SIGNIFICANCE: After a dilated eye examination, many patients experience symptoms of prolonged light sensitivity, blurred vision, and cycloplegia associated with pharmacological mydriasis. Phentolamine mesylate ophthalmic solution (PMOS) may expedite the reversal of mydriasis in patients, potentially facilitating return to functional vision and reducing barriers to obtaining dilated eye examinations. PURPOSE: The protracted reversal time after pharmacologically induced pupil dilation impairs vision. We tested the hypothesis that PMOS rapidly reduces pupil diameter in this acute indication. METHODS: In this double-masked placebo-controlled, randomized, two-arm crossover phase 2b trial, we evaluated the effects of one drop of 1% PMOS applied bilaterally in subjects who had their pupils dilated by one of two common mydriatic agents: 2.5% phenylephrine or 1% tropicamide. End points included change in pupil diameter, percent of subjects returning to baseline pupil diameter, and accommodative function at multiple time points. RESULTS: Thirty-one subjects completed the study (15 dilated with phenylephrine and 16 with tropicamide). Change in pupil diameter from baseline at 2 hours after maximal dilation with 1% PMOS was -1.69 mm and was significantly greater in magnitude compared with placebo for every time point beyond 30 minutes (P < .05). At 2 hours, a greater percentage of study eyes given 1% PMOS returned to baseline pupil diameter compared with placebo (29 vs. 13%, P = .03), which was this also seen at 4 hours (P < .001). More subjects treated with PMOS in the tropicamide subgroup had at least one eye returning to baseline accommodative amplitude at 2 hours (63 vs. 38%, P = .01). There were no severe adverse events, with only mild to moderate conjunctival hyperemia that resolved in most patients by 6 hours. CONCLUSIONS: Phentolamine mesylate ophthalmic solution at 1% reversed medically induced pupil dilation more rapidly than placebo treatment regardless of which mydriatic was used (adrenergic agonists and cholinergic blockers) with a tolerable safety profile.

Phentolamine Mesylate Ophthalmic Solution Provides Lasting Pupil Modulation and Improves Near Visual Acuity in Presbyopic Glaucoma Patients in a Randomized Phase 2b Clinical Trial.

PURPOSE: Phentolamine mesylate ophthalmic solution (PMOS), applied to the eye topically, was shown previously to have beneficial effects in patients with dim light vision disturbances (DLD), including decreased pupil diameter (PD), improved best-corrected distance visual acuity (BCDVA), as well as lower intraocular pressure (IOP). The ORION-1 trial evaluated the long-term safety and efficacy of PMOS in a glaucomatous, presbyopic population. PATIENTS AND METHODS: In this randomized, double-masked, multi-center, placebo-controlled, multiple-dose Phase 2b trial, 39 patients with elevated IOP were randomized to receive one evening dose of study medication or placebo for 14 days. The primary outcome measure was mean change in diurnal IOP, and the key secondary outcome measures included changes in PD, distance-corrected near visual acuity (DCNVA), and conjunctival hyperemia. RESULTS: Use of 1% PMOS did not lead to a statistically significant decrease in diurnal IOP compared to placebo (P = 0.89) but trended toward a greater decrease in patients with lower IOP baselines. PMOS produced a statistically significant mean 20% PD reduction under both photopic and mesopic conditions that was sustained for 36 hours post-dosing. A statistically significant number of patients with PMOS compared to placebo demonstrated ≥1 line of improvement in photopic DCNVA at day 8 (P = 0.0018), day 15 (P = 0.0072), and day 16 (P = 0.0163), with a trend for 2- and 3-line improvements at all time points. There was no statistical difference in conjunctival hyperemia compared to placebo. CONCLUSION: Although mean IOP was not lowered significantly, daily evening dosing of 1% PMOS was found to be well tolerated with no daytime conjunctival redness and demonstrated improvement in DCNVA with sustained PD reduction in a glaucomatous and presbyopic population. Smaller pupil size can have beneficial effects in improving symptoms of presbyopia and DLD, which will be the focus of further studies.

Dry Eye Disease: Consideration for Women's Health.

Dry eye disease (DED) is a multifactorial disorder of the ocular surface and tear homeostasis that can result in discomfort, pain, and visual disturbance. Untreated, DED can become chronic, progressive, and significantly affect an individual's quality of life. Women are disproportionately affected by DED, are diagnosed at a younger age, and experience more severe symptoms compared with men. DED is associated with a wide range of comorbid conditions; there is a strong association between DED and autoimmune disorders, especially those that affect women at many times the rate of men. Treatment response questionnaires indicate women respond better to a wellness model of treatment for DED than men. Furthermore, women's health care-seeking behaviors provide opportunities for general practitioners, specialists, and women's health centers to help identify women with DED or at risk for DED for referral to an eye care specialist. This review of the prevalence of DED in women, and gender and sex-specific aspects of DED, highlight a significant opportunity for action. Earlier diagnosis and treatment of this common but burdensome condition could significantly improve a woman's quality of life.

Treatment outcomes in the DRy Eye Amniotic Membrane (DREAM) study.

PURPOSE: To evaluate the efficacy of cryopreserved amniotic membrane (CAM) in reducing signs and symptoms of dry eye disease (DED) in a large patient population. METHODS: A retrospective chart review at 10 clinical sites was done of patients with refractory DED who received CAM and completed at least 3 months of follow-up. Data collected were demographics; medical history including previous and current ocular treatment, diagnosis, clinical presentations, comorbidity, duration and frequency of treatment with CAM; and concomitant medications. The primary outcome was the change in dry eye workshop (DEWS) score after treatment. RESULTS: A total of 97 eyes of 84 patients exhibited severe dry eye despite maximal medical treatments including topical artificial tears, cyclosporine-A, serum, antibiotics, and steroids. Patients manifested with superficial punctate keratitis (86%), filamentary keratitis (13%), exposure keratitis (19%), neurotrophic keratitis (2%), and corneal epithelial defect (7%). After CAM treatment for 5.4±2.8 days, 74 (88%) patients demonstrated an improved ocular surface along with a notable reduction of the severity as the overall DEWS score was significantly reduced from 3.25±0.5 at baseline to 1.44±0.6 at 1 week, 1.45±0.6 at 1 month, and 1.47±0.6 at 3 months (p<0.001). Ten eyes (10%) required repeated treatment to complete healing. Apart from discomfort during CAM placement, there were no adverse events. CONCLUSION: Placement of CAM is promising to enhance the recovery of ocular surface health and reduce signs and symptoms in patients with moderate-to-severe DED.

The Prospective Health Assessment of Cataract Patients' Ocular Surface (PHACO) study: the effect of dry eye.

PURPOSE: To determine the incidence and severity of dry eye as determined by the International Task Force (ITF) scale in patients being screened for cataract surgery. PATIENTS AND METHODS: This was a prospective, multi-center, observational study of 136 patients, at least 55 years of age, who were scheduled to undergo cataract surgery. The primary outcome measure was the incidence of dry eye as evaluated by grade on the ITF scale and secondary outcome measures include tear break-up time (TBUT), ocular surface disease index score, corneal staining with fluorescein, conjunctival staining with lissamine green, and a patient questionnaire to evaluate symptoms of dry eye. RESULTS: Mean patient age was 70.7 years. A total of 73.5% of patients were Caucasian and 50% were female. Almost 60% had never complained of a foreign body sensation; only 13% complained of a foreign body sensation half or most of the time. The majority of patients (62.9%) had a TBUT ≤5 seconds, 77% of eyes had positive corneal staining and 50% of the eyes had positive central corneal staining. Eighteen percent had Schirmer's score with anesthesia ≤5 mm. CONCLUSION: The incidence of dry eye in patients scheduled to undergo cataract surgery in a real-world setting is higher than anticipated.

Dysfunctional tear syndrome: dry eye disease and associated tear film disorders - new strategies for diagnosis and treatment.

Dysfunctional tear syndrome (DTS) is a common and complex condition affecting the ocular surface. The health and normal functioning of the ocular surface is dependent on a stable and sufficient tear film. Clinician awareness of conditions affecting the ocular surface has increased in recent years because of expanded research and the publication of diagnosis and treatment guidelines pertaining to disorders resulting in DTS, including the Delphi panel treatment recommendations for DTS (2006), the International Dry Eye Workshop (DEWS) (2007), the Meibomian Gland Dysfunction (MGD) Workshop (2011), and the updated Preferred Practice Pattern guidelines from the American Academy of Ophthalmology pertaining to dry eye and blepharitis (2013). Since the publication of the existing guidelines, new diagnostic techniques and treatment options that provide an opportunity for better management of patients have become available. Clinicians are now able to access a wealth of information that can help them obtain a differential diagnosis and treatment approach for patients presenting with DTS. This review provides a practical and directed approach to the diagnosis and treatment of patients with DTS, emphasizing treatment that is tailored to the specific disease subtype as well as the severity of the condition.

Regulation of proinflammatory genes by the circulating microRNA hsa-miR-939.

Circulating microRNAs are beneficial biomarkers because of their stability and dysregulation in diseases. Here we sought to determine the role of miR-939, a miRNA downregulated in patients with complex regional pain syndrome (CRPS). Hsa-miR-939 is predicted to target several proinflammatory genes, including IL-6, VEGFA, TNFα, NFκB2, and nitric oxide synthase 2 (NOS2A). Binding of miR-939 to the 3' untranslated region of these genes was confirmed by reporter assay. Overexpression of miR-939 in vitro resulted in reduction of IL-6, NOS2A and NFκB2 mRNAs, IL-6, VEGFA, and NOS2 proteins and NFκB activation. We observed a significant decrease in the NOS substrate l-arginine in plasma from CRPS patients, suggesting reduced miR-939 levels may contribute to an increase in endogenous NOS2A levels and NO, and thereby to pain and inflammation. Pathway analysis showed that miR-939 represents a critical regulatory node in a network of inflammatory mediators. Collectively, our data suggest that miR-939 may regulate multiple proinflammatory genes and that downregulation of miR-939 in CRPS patients may increase expression of these genes, resulting in amplification of the inflammatory pain signal transduction cascade. Circulating miRNAs may function as crucial signaling nodes, and small changes in miRNA levels may influence target gene expression and thus disease.

Economic and Humanistic Burden of Dry Eye Disease in Europe, North America, and Asia: A Systematic Literature Review.

Dry eye disease (DED) is a chronic and progressive multifactorial disorder of the tears and ocular surface, which results in symptoms of discomfort and visual disturbance. The aim of this systematic literature review was to evaluate the burden of DED and its components from an economic and health-related quality of life (HRQoL) perspective, and to compare the evidence across France, Germany, Italy, Spain, UK, USA, Japan, and China. PubMed, Embase, and six other resources were searched for literature published from January 1998 to July 2013. Of 76 titles/abstracts reviewed on the economic burden of DED and 263 on the HRQoL burden, 12 and 20 articles, respectively, were included in the review. The available literature suggests that DED has a substantial economic burden, with indirect costs making up the largest proportion of the overall cost due to a substantial loss of work productivity. In addition, DED has a substantial negative impact on physical, and potentially psychological, function and HRQoL across the countries examined. A number of studies also indicated that HRQoL burden increases with the severity of disease. Additional data are needed, particularly in Asia, in order to gain a better understanding of the burden of DED and help inform future health care resource utilization.

Circulating microRNA Signatures in Rodent Models of Pain.

MicroRNAs (miRNAs) remain stable in circulation and have been identified as potential biomarkers for a variety of conditions. We report miRNA changes in blood from multiple rodent models of pain, including spinal nerve ligation and spared nerve injury models of neuropathic pain; a complete Freund's adjuvant (CFA) model of inflammatory pain; and a chemotherapy-induced model of pain using the histone deacetylase inhibitor JNJ-26481585. The effect of celecoxib, a cyclooxygenase-2-selective nonsteroidal anti-inflammatory drug, was investigated in the CFA model as proof of principle for assessing the utility of circulating miRNAs as biomarkers in determining treatment response. Each study resulted in a unique miRNA expression profile. Despite differences in miRNAs identified from various models, computational target prediction and functional enrichment have identified biological pathways common among different models. The Wnt signaling pathway was affected in all models, suggesting a crucial role for this pathway in the pathogenesis of pain. Our studies demonstrate the utility of circulating miRNAs as pain biomarkers and suggest the potential for rigorous forward and reverse translational approaches. Evaluating alterations in miRNA fingerprints under different pain conditions and after administering therapeutic agents may be beneficial in evaluating clinical trial outcomes, predicting treatment response, and developing correlational outcomes between preclinical and human studies.

Screening Patients With Cataract for Premium IOL Candidacy Using Microperimetry.

PURPOSE: To explore the use of microperimetry in the evaluation of macular dysfunction in patients with cataract, to aid in proper intraocular lens selection (multifocal vs monofocal), and to set expectations for postoperative visual function. METHODS: One randomly chosen eye of 10 patients diagnosed as having mild (1+) to moderate (3+) cataract was evaluated before and 1 week after cataract surgery with the MAIA microperimeter (Centervue S.p.A, Padova, Italy). Corrected distance visual acuity, dilated and undilated biomicroscopy and indirect fundus examinations, intraocular pressure measurement, and a MAIA microperimeter test to measure macular sensitivity and fixation pattern were also performed. RESULTS: Two patients showed macular abnormalities before and after surgery that were noted on MAIA testing: one patient showed reduced average threshold sensitivity and abnormal percent reduced threshold, whereas the other patient showed fixation drift demonstrating eccentric fixation. Both eyes had reduced postoperative visual performance after uneventful cataract surgeries. CONCLUSIONS: Because not every macular lesion noted on fundus examination or optical coherence tomography may be clinically significant, microperimetry can be useful to detect clinically significant retinal dysfunction prior to cataract surgery. The outcome may aid in the selection of intraocular lens type and may yield a better documented surgical prognosis. Further studies are necessary to confirm these findings.

MicroRNA biology and pain.

Endogenously expressed small noncoding microRNAs (miRNAs) play an important role in posttranscriptionally regulating gene expression by binding to mRNAs with complementary sequences. miRNA-mRNA interactions allow for cellular flexibility to fine-tune gene expression by controlling translation in response to a multitude of signaling events. Disease states or perturbations in cellular homeostasis can lead to aberrant miRNA expression. The discovery of stable miRNAs in circulation generated enormous interest in exploring their utility as potential noninvasive biomarkers. Additionally, selectively inhibiting or supplementing an miRNA contributing to pathogenesis is being pursued as a therapeutic strategy for a variety of disorders. Studies from rodent models of pain and patients have now implicated a role for miRNAs in mediating various aspects of pain processing. These noncoding RNAs can provide mechanistic insights into the pathways modulated and could serve as therapeutic targets. Here, we discuss the challenges associated with miRNA research and the promises ahead in this vastly unexplored avenue in pain biology.

Antibiotic resistance in acute postoperative endophthalmitis.

Acute postoperative endophthalmitis (APE) is a serious, although infrequent, complication of eye surgery that can result in significant morbidity and costs. This review addresses APE risk factors, associated bacterial pathogens, antibiotic resistance, and prevention.