Inflammation of Dry Eye Syndrome: A Cellular Study of the Epithelial and Macrophagic Involvement of NFAT5 and RAGE.

Dry eye inflammation is a key step in a vicious circle and needs to be better understood in order to break it. The goals of this work were to, first, characterize alarmins and cytokines released by ocular surface cells in the hyperosmolar context and, second, study the role of NFAT5 in this process. Finally, we studied the potential action of these alarmins in ocular surface epithelial cells and macrophages via RAGE pathways. HCE and WKD cell lines were cultured in a NaCl-hyperosmolar medium and the expression of alarmins (S100A4, S100A8, S100A9, and HMGB1), cytokines (IL6, IL8, TNFα, and MCP1), and NFAT5 were assessed using RT-qPCR, ELISA and multiplex, Western blot, immunofluorescence, and luciferase assays. In selected experiments, an inhibitor of RAGE (RAP) or NFAT5 siRNAs were added before the hyperosmolar stimulations. HCE and WKD cells or macrophages were treated with recombinant proteins of alarmins (with or without RAP) and analyzed for cytokine expression and chemotaxis, respectively. Hyperosmolarity induced epithelial cell inflammation depending on cell type. NFAT5, but not RAGE or alarmins, participated in triggering epithelial inflammation. Furthermore, the release of alarmins induced macrophage migration through RAGE. These in vitro results suggest that NFAT5 and RAGE have a role in dry eye inflammation.

Efficacy of treatments for neurotrophic keratopathy: a systematic review and meta-analysis.

PURPOSE: Management of NK can be difficult, involving a range of treatments with variable efficacy. We conducted a systematic review and meta-analysis to evaluate the efficacy of medical and surgical treatments for neurotrophic keratitis (NK). METHOD: PubMed, Cochrane Library, Embase, ClinicalTrial.gov, and ScienceDirect were searched for studies assessing efficacy of NK treatments. We computed random-effect meta-analyses on corneal healing, time to complete healing, and visual acuity changes between baselines and after treatment, stratified on treatment classes. We followed the PRISMA guidelines (registration number CRD42021225721). RESULTS: We included 20 studies: 571 patients and 5 treatment classes (2 surgical and 3 non-surgical). The percentage of patients with complete corneal healing did not differ between specific treatments (nerve growth factor eyedrops (NGF), 75%, 95CI 46 to 104%; autologous serum (AS), 92%, 86 to 98%; neurotization, 99%, 95 to 103%; amniotic membrane transplantation (AMT), 86%, 78 to 94%). All specific treatments had better percentage of complete healing (p < 0.001) than non-specific treatment groups, i.e., mainly lubricants (23%, 14 to 32). Time to complete healing was 24.2 days (5.4 to 43.1) with NGF, 27.6 days (15.2 to 40.0) with AS, 117 days (28.8 to 205.2) with neurotization, and 16.4 days (11.1 to 21.7) with AMT. Only NGF and AMT improved visual acuity. Efficacy outcomes were not affected by sociodemographic (age, sex) nor severity of disease (Mackie stages). CONCLUSION: We confirmed the efficacy of specific treatments in NK. Further comparative trials are needed to investigate the medical and economic benefits of innovative therapies.

Benefits of using corneal topography to choose subjective refraction technique in keratoconus (RE-CON): a prospective comparative crossover clinical study.

PURPOSE: In prospective no-masking, comparative, crossover monocenter clinical trial, we aimed to evaluate whether the optimal subjective refraction technique varies with the keratoconus topography and to identify relevant topographic criteria. METHOD: This study included 72 keratoconus eyes with impaired visual acuity. Each eye tested three methods of refraction (Jackson cylinder, astigmatism dial, stenopeic slit), resulting in three eyeglass lenses. Patients were assigned to the group corresponding to the eyeglass lens offering the best visual acuity. Five topographical characteristics were collected via the Pentacam: mean keratometry (Km), maximum keratometry (Kmax), distance from corneal center to Kmax (dKmax), Belin/Ambrosio Display (BAD_D), and index of surface variance (ISV). RESULTS: Forty-six eyes were included in the dial group (64.8%), 23 eyes in the cylinder group (32.4%), and only 2 eyes in the slit group (2.8%); thus, we only compared dial and cylinder groups. The main analysis retrieved a significant probability to choose dial technic for BAD_D (p = 0.024); when BAD_D is > 9.71 (ROC threshold), the positive predictive value (PPV) = 89.5%, and for ISV, p = 0.012; when ISV is > 77, PPV = 89.1%. The sub-analysis of patients with different visual acuities between cylinder and dial confirmed these results with slightly different thresholds: the probability to choose dial technic was for BAD_D, p = 0.03; when BAD_D is > 7.55, PPV = 90%, and for ISV, p = 0.0084; when ISV is > 71, PPV = 88.5%. CONCLUSION: Refraction method is linked to topographic indices ISV and BAD_D. A BAD_D > 7.55 indicates the dial method. In addition to keratoconus screening and diagnosis, this study suggests a new application of the topographer to select a suitable refraction method for eyeglass prescription. TRIAL REGISTRATION: Study registered on the ClinicalTrials.gov database under n°: NCT04174209.

Efficacy of medical treatments for vernal keratoconjunctivitis: A systematic review and meta-analysis.

BACKGROUND: Vernal keratoconjunctivitis (VKC) is a severe type of allergic conjunctivitis for which treatment strategies are still under debate. OBJECTIVES: This study sought to conduct a systematic review and meta-analysis to evaluate the efficacy of medical treatments for VKC. METHODS: The PubMed, Cochrane Library, Embase, and ScienceDirect databases were searched to assess the efficacy of treatments for VKC. Random-effect meta-analyses on changes in clinical scores of symptoms and signs between baseline and after treatment, stratified on treatment classes, were computed. Meta-regressions were searched for potential influencing parameters. RESULTS: Included were 45 studies (27 randomized controlled trials and 18 prospective cohort studies), 1749 patients (78% were men; mean age, 11.2 years), and 12 different treatment classes. Mast cell stabilizers (MCSs; usually considered as first-line therapy), cyclosporine, and tacrolimus were the most studied drugs (in three-quarters of studies). Overall, all clinical scores improved. Total symptom and sign score decreased for MCSs (effect size, -3.19; 95% CI, -4.26 to -2.13), cyclosporine (effect size, -2.06; 95% CI, -2.72 to -1.40), and tacrolimus (effect size, -2.39; 95% CI, -3.36 to -1.43). No significant differences were shown depending on treatment classes, concentration, age, sex, baseline activity scores, and atopy. Sensitivity analyses demonstrated similar results. CONCLUSIONS: This study confirms the efficacy of MCSs in the treatment of VKC. Efficacy of cyclosporine and tacrolimus did not differ, suggesting that tacrolimus is a good alternative to cyclosporine for severe cases of VKC. Further studies are needed to compare other drugs and their precise place in treatment strategy.

PTSD as the second tsunami of the SARS-Cov-2 pandemic.

Since the first cases, the coronavirus disease (COVID-19) rapidly spread around the world, with hundred-thousand cases and thousands of deaths. Post-traumatic stress disorder (PTSD) is a common consequence of major disasters. Exceptional epidemic situations also promoted PTSD in the past. Considering that humanity is undergoing the most severe pandemic since Spanish Influenza, the actual pandemic of COVID-19 is very likely to promote PTSD. Moreover, COVID-19 was renamed severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). With a poor understanding of viruses and spreading mechanisms, the evocation of SARS is generating a great anxiety contributing to promote PTSD. Quarantine of infected patients evolved to quarantine of 'infected' towns or popular districts, and then of entire countries. In the families of cases, the brutal death of family members involved a spread of fear and a loss of certainty, promoting PTSD. In the context of disaster medicine with a lack of human and technical resources, healthcare workers could also develop acute stress disorders, potentially degenerating into chronic PTSD. Globally, WHO estimates 30-50% of the population affected by a disaster suffered from diverse psychological distress. PTSD individuals are more at-risk of suicidal ideation, suicide attempt, and deaths by suicide - considering that healthcare workers are already at-risk occupations. We draw attention towards PTSD as a secondary effect of the SARS-Cov-2 pandemic, both for general population, patients, and healthcare workers. Healthcare policies need to take into account preventive strategy of PTSD, and the related risk of suicide, in forthcoming months.

Deep learning versus ophthalmologists for screening for glaucoma on fundus examination: A systematic review and meta-analysis.

BACKGROUND: In this systematic review and meta-analysis, we aimed to compare deep learning versus ophthalmologists in glaucoma diagnosis on fundus examinations. METHOD: PubMed, Cochrane, Embase, ClinicalTrials.gov and ScienceDirect databases were searched for studies reporting a comparison between the glaucoma diagnosis performance of deep learning and ophthalmologists on fundus examinations on the same datasets, until 10 December 2020. Studies had to report an area under the receiver operating characteristics (AUC) with SD or enough data to generate one. RESULTS: We included six studies in our meta-analysis. There was no difference in AUC between ophthalmologists (AUC = 82.0, 95% confidence intervals [CI] 65.4-98.6) and deep learning (97.0, 89.4-104.5). There was also no difference using several pessimistic and optimistic variants of our meta-analysis: the best (82.2, 60.0-104.3) or worst (77.7, 53.1-102.3) ophthalmologists versus the best (97.1, 89.5-104.7) or worst (97.1, 88.5-105.6) deep learning of each study. We did not retrieve any factors influencing those results. CONCLUSION: Deep learning had similar performance compared to ophthalmologists in glaucoma diagnosis from fundus examinations. Further studies should evaluate deep learning in clinical situations.

Irregular Astigmatism Management Using SPOT Scleral Lenses in the Treatment of Corneal Ectasia and Penetrating Keratoplasty.

PURPOSE: To evaluate the outcome of SPOT scleral lenses in the management of irregular astigmatism in patients with corneal ectasia and penetrating keratoplasty. Second, we analyzed patients' characteristics and tolerance, comfort, and geometries of fitted lenses. METHOD: Over a 5-year period, we included patients experiencing irregular astigmatism fitted with SPOT scleral contact lenses, from the University Hospital of Clermont-Ferrand, France. Data collected included corneal diseases, refractive error, best-corrected visual acuity (VA) with SPOT lenses, geometry of the lens, number of adjustment consultations, and the duration of follow-up. Comfort, quality of vision, less handling, and satisfaction were evaluated using visual analog scales after a 6-month follow-up period. RESULTS: Sixty-five patients were included, analyzing 107 eyes. Eighty percent of patients still daily wore lenses after a follow-up of 22.3±13.8 months. Visual acuity improved by 0.47±0.51 logarithm of the minimum angle of resolution (average increase of 5 lines) (P<0.001) after wearing scleral lenses. Comfort, quality of vision, less handling, and satisfaction of contact lenses were excellent (>75/100). Contact lenses were daily worn 10.0±4.1 hr/day. Most patients wore size M (17 mm) lenses (53.3% of patients), with an average sagittal height of 5.2±1.2 mm. Internal toricity was used in 30% of cases. Best geometry was found after 2.69±0.87 consultations. CONCLUSION: SPOT scleral contact lenses are an effective and well tolerated method to improve the VA of patients with irregular astigmatism.

Myopia and Near Work: A Systematic Review and Meta-Analysis.

BACKGROUND: Myopia is a global public health problem affecting quality of life and work productivity. Data is scarce regarding the effects of near work on myopia. Providing a larger meta-analysis with life-long perspective, including adults and occupational exposure seemed needed. METHODS: We searched PubMed, Cochrane Library, Embase and Science Direct for studies reporting myopia prevalence in near work. Myopia was defined as a mean spherical equivalent ≤ -0.50 diopter. We performed a meta-analysis using random-effects model on myopia prevalence, myopia progression per year, and odds ratio (OR) of myopia in near work, completed by subgroup analyses and meta-regressions on patients' characteristics, type of work in adults, geographic zones, time and characteristics of near work. RESULTS: We included 78 studies, representing a total of 254,037 participants, aged from 6 to 39 years. The global prevalence of myopia in near work was 35% (95% CI: 30 to 41%), with a prevalence of 31% (95% CI: 26 to 37%) in children and 46% (95% CI: 30 to 62%) in adults. Myopia progression was -0.39 diopters per year (-0.53 to -0.24 D/year), ranging from -0.44 (-0.57 to -0.31) in children to -0.25 D/year (-0.56 to 0.06) in adults. The odds of myopia in workers exposed vs. non-exposed to near work were increased by 26% (18 to 34%), by 31% (21 to 42%) in children and 21% (6 to 35%) in adults. Prevalence of myopia was higher in adults compared to children (Coefficient 0.15, 95% CI: 0.03 to 0.27). CONCLUSIONS: Near work conditions, including occupational exposure in adults, could be associated with myopia. Targeted prevention should be implemented in the workplace.

Preventive treatment of allograft rejection after endothelial keratoplasty: A systematic review and meta-analysis.

PURPOSE: To evaluate the efficacy of preventive treatment against allograft rejection after endothelial keratoplasty (EK), we conducted a systematic review and meta-analysis. METHOD: PubMed, Cochrane Library, Embase and ScienceDirect databases were searched until May 2021. We computed a random-effect meta-analysis on graft rejection rate stratified by the intervention (i.e. Descemet membrane EK (DMEK) and Descemet stripping (Automated) EK (DS(A)EK) or ultrathin (UT)-DSAEK), and postoperative treatment. Meta-regressions were performed to compare intervention, treatment and influence of putative confusion factors. RESULTS: We included 49 studies and 12 893 EK (6867 DMEK and 6026 DS(A)EK/UT-DSAEK). Topical steroids were merged in two efficacy regimens: standard steroids (prednisolone acetate 1% or dexamethasone 0.1%) and soft steroids (fluorometholone 0.1% or loteprednol etabonate 0.5%). Globally, DMEK had a lower graft rejection rate than DS(A)EK/UT-DSAEK (coefficient - 3.3, 95 CI, -4.60 to -1.90; p < 0.001). No significant differences were observed between standard and soft steroids to prevent graft rejection after DMEK. After EK, the rate of ocular hypertension was 20% (95 CI, 14 to 26%) with the use of standard steroids and 7% (5 to 9%) with soft steroids. Comparisons of treatments were not feasible in DS(A)EK/UT-DSAEK due to a lack of studies. CONCLUSIONS: Descemet membrane endothelial keratoplasty (DMEK) has less risk of graft rejection compared with DS(A)EK/UT-DSAEK. Furthermore, soft steroids seemed to be a valuable alternative to standard steroids to prevent graft rejection after DMEK, involving a safe profile against ocular hypertension. Further studies are needed to compare other drugs in the prevention of graft rejection after EK.

Oxidative and antioxidative stress markers in dry eye disease: A systematic review and meta-analysis.

PURPOSE: To conduct a systematic review and meta-analysis on the levels of oxidative stress markers and antioxidants in dry eye disease (DED) compared with healthy subject. METHOD: The PubMed, Cochrane Library, Embase, Science Direct and Google Scholar databases were searched on 10 January 2021 for studies reporting oxidative and antioxidative stress markers in DED and healthy controls. Main meta-analysis was stratified by type of biomarkers, type of samples (tears, conjunctival cells or biopsies), Sjögren's syndrome (SS) (patients with or without SS) and by geographical zones (Asia or Europe). RESULTS: We included nine articles, for a total of 333 patients (628 eye samples) with DED and 165 healthy controls (451 eye samples). There is an overall increase in oxidative stress markers in DED compared with healthy controls (standard mean deviation = 2.39, 95% confidence interval 1.85-2.94), with a significant increase in lipid peroxide (1.90, 0.69-3.11), myeloperoxidase (2.17, 1.06-3.28), nitric oxide synthase 3 (2.52, 0.95-4.08), xanthine oxidase/oxidoreductase (2.41, 1.40-5.43), 4-hydroxy-2-nonenal (4HNE) (4.75, 1.67-7.84), malondialdehyde (3.00, 2.55-3.45) and reactive oxygen species (1.31, 0.94-1.68). Oxidative stress markers were higher in tears, conjunctival cells and conjunctival biopsies of DED than controls. Even if small number of studies were included for antioxidants, catalase seemed to be decreased in DED compared with healthy controls (-2.17, -3.00 to -1.34), with an increase of antioxidants in tears of DED patients without SS (1.13, 0.76-1.49). CONCLUSION: Oxidative stress markers, and probably antioxidants, were dysregulated in DED, establishing a local oxidative environment in tears, conjunctival cells and tissues.

Complications of Adenoviral Keratoconjunctivitis in Ophthalmologists and Orthoptists: Epidemiology and Risk Factor, A Retrospective Questionnaire Analysis.

PURPOSE: The purpose of this study was to assess the medical history of adenoviral keratoconjunctivitis (AK) and subepithelial infiltrates (SEIs) among French ophthalmologists and orthoptists and the frequency of unreported occupational diseases. We also described short-term and long-term consequences of AK and evaluated associated factors. METHODS: The REDCap questionnaire was diffused online several times over 7 consecutive months, from October 2019 to May 2020, through mailing lists (French Society of Ophthalmology, residents, and hospital departments), social networks, and by word of mouth. RESULTS: Seven hundred ten participants were included with a response rate of 6.2% for ophthalmologists, 3.8% for orthoptists, and 28.3% for ophthalmology residents. The medical history of AK was found in 24.1% (95% confidence interval 21%-27.2%) of respondents and SEI in 43.9% (36.5%-51.3%) of the AK population. In total, 87.1% (82.1%-92.1%) of AK occupational diseases were not declared. In total, 57.7% of respondents took 9.4 ± 6.2 days of sick leave, mostly unofficial, and 95.7% stopped surgeries for 13.0 ± 6.6 days. Among the AK population, 39.8% had current sequelae, with 17.5% having persistent SEIs, 19.9% using current therapy, and 16.4% experiencing continuing discomfort. SEIs were associated with wearing contact lenses (odds ratio 3.31, 95% confidence interval 1.19-9.21) and smoking (4.07, 1.30-12.8). Corticosteroid therapy was associated with a greater number of sequelae (3.84, 1.51-9.75). CONCLUSIONS: AK and SEI affect a large proportion of ophthalmologists and orthoptists, possibly for years, with high morbidity leading to occupational discomfort. Few practitioners asked for either to be recognized as an occupational disease. Associated factors would require a dedicated study.

Descemetorhexis Without Endothelial Keratoplasty in Fuchs Endothelial Corneal Dystrophy: A Systematic Review and Meta-Analysis.

PURPOSE: Descemetorhexis without endothelial keratoplasty (DWEK) is an innovative corneal intervention and potentially effective against Fuchs endothelial corneal dystrophy (FECD). We aimed to conduct a systematic review and meta-analysis on the outcomes of DWEK, associated or not with phacoemulsification (PKE) and rho-kinase inhibitor (RHOKI) in FECD. METHOD: PubMed, Cochrane Library, Embase, ClinicalTrials.gov , and Science Direct were searched for studies until November 29, 2020. We performed random-effects meta-analyses and meta-regressions, stratified by the type of intervention and descemetorhexis size (PROSPERO CRD42020167566). RESULTS: We included 11 articles (mainly case series, both prospective and retrospective), representing 127 eyes of 118 patients. DWEK globally improved visual acuity (effect size = -1.11, 95% confidence interval, -1.70 to -0.52, P < 0.001) and pachymetry (-1.25, -1.92 to -0.57, P < 0.001), without significant effects on endothelial cell count (-0.59, -2.00 to 0.83, P = 0.419). The 3 types of interventions (ie, DWEK ± RHOKI, DWEK ± PKE, and DWEK ± PKE ± RHOKI) improved visual acuity and pachymetry in FECD. A descemetorhexis size ≤4 mm improved visual acuity (-0.72, -1.29 to -0.14, P < 0.001) and pachymetry (-0.68, -0.98 to -0.38, P < 0.001), whereas >4 mm did not. Overall, DWEK failure (ie, the prevalence of EK after DWEK) was 17% (7%-27%, P < 0.001), with 4% (0%-8%, P = 0.08) for a descemetorhexis size ≤4 mm. CONCLUSIONS: Despite the lack of comparative studies, DWEK seemed to improve visual acuity and pachymetry in early stages of FECD. A descemetorhexis size ≤4 mm was associated with the best visual outcomes and pachymetry.

Heart rate variability in hypothyroid patients: A systematic review and meta-analysis.

INTRODUCTION: Hypothyroidism may be associated with changes in the autonomic regulation of the cardiovascular system, which may have clinical implications. OBJECTIVE: To conduct a systematic review and meta-analysis on the impact of hypothyroidism on HRV. MATERIALS AND METHODS: PubMed, Cochrane, Embase and Google Scholar were searched until 20 August 2021 for articles reporting HRV parameters in untreated hypothyroidism and healthy controls. Random-effects meta-analysis were stratified by degree of hypothyroidism for each HRV parameters: RR intervals (or normal to normal-NN intervals), SDNN (standard deviation of RR intervals), RMSSD (square root of the mean difference of successive RR intervals), pNN50 (percentage of RR intervals with >50ms variation), total power (TP), LFnu (low-frequency normalized unit), HFnu (high-frequency), VLF (very low frequency), and LF/HF ratio. RESULTS: We included 17 studies with 11438 patients: 1163 hypothyroid patients and 10275 healthy controls. There was a decrease in SDNN (effect size = -1.27, 95% CI -1.72 to -0.83), RMSSD (-1.66, -2.32 to -1.00), pNN50 (-1.41, -1.98 to -0.84), TP (-1.55, -2.1 to -1.00), HFnu (-1.21, -1.78 to -0.63) with an increase in LFnu (1.14, 0.63 to 1.66) and LF/HF ratio (1.26, 0.71 to 1.81) (p <0.001). HRV alteration increased with severity of hypothyroidism. CONCLUSIONS: Hypothyroidism is associated with a decreased HRV, that may be explained by molecular mechanisms involving catecholamines and by the effect of TSH on HRV. The increased sympathetic and decreased parasympathetic activity may have clinical implications.

Metabolic syndrome and pesticides: A systematic review and meta-analysis.

The relation between pesticides exposure and metabolic syndrome (MetS) has not been clearly identified. Performing a systematic review and meta-analysis, PubMed, Cochrane Library, Embase, and ScienceDirect were searched for studies reporting the risk of MetS following pesticides exposure and their contaminants. We included 12 studies for a total of 6789 participants, in which 1981 (29.1%) had a MetS. Overall exposure to pesticides and their contaminants increased the risk of MetS by 30% (95CI 22%-37%). Overall organochlorine increased the risk of MetS by 23% (14-32%), as well as for most types of organochlorines: hexachlorocyclohexane increased the risk by 53% (28-78%), hexachlorobenzene by 40% (0.01-80%), dichlorodiphenyldichloroethylene by 22% (9-34%), dichlorodiphenyltrichloroethane by 28% (5-50%), oxychlordane by 24% (1-47%), and transnonchlor by 35% (19-52%). Sensitivity analyses confirmed that overall exposure to pesticides and their contaminants increased the risk by 46% (35-56%) using crude data or by 19% (10-29%) using fully-adjusted model. The risk for overall pesticides and types of pesticides was also significant with crude data but only for hexachlorocyclohexane (36% risk increase, 17-55%) and transnonchlor (25% risk increase, 3-48%) with fully-adjusted models. Metaregressions demonstrated that hexachlorocyclohexane increased the risk of MetS in comparison to most other pesticides. The risk increased for more recent periods (Coefficient = 0.28, 95CI 0.20 to 0.37, by year). We demonstrated an inverse relationship with body mass index and male gender. In conclusion, pesticides exposure is a major risk factor for MetS. Besides organochlorine exposure, data are lacking for other types of pesticides. The risk increased with time, reflecting a probable increase of the use of pesticides worldwide. The inverse relationship with body mass index may signify a stockage of pesticides and contaminants in fat tissue.

Heart Rate Variability in Hyperthyroidism: A Systematic Review and Meta-Analysis.

Objective: Cardiovascular effects of thyroid hormones may be measured through heart rate variability (HRV). We sought to determine the impact of hyperthyroidism on HRV. Design: A systematic review and meta-analysis on the impact of hyperthyroidism on HRV. Methods: PubMed, Cochrane, Embase and Google Scholar were searched until 20 August 2021 for articles reporting HRV parameters in untreated hyperthyroidism and healthy controls. Random-effects meta-analysis was stratified by degree of hyperthyroidism for each HRV parameter: RR intervals (or Normal-to-Normal intervals­NN), SDNN (standard deviation of RR intervals), RMSSD (square root of the mean difference of successive RR intervals), pNN50 (percentage of RR intervals with >50 ms of variation), total power (TP), LFnu (low-frequency normalized unit) and HFnu (high-frequency), VLF (very low-frequency), and LF/HF ratio. Results: We included 22 studies with 10,811 patients: 1002 with hyperthyroidism and 9809 healthy controls. There was a decrease in RR (effect size = −4.63, 95% CI −5.7 to −3.56), SDNN (−6.07, −7.42 to −4.71), RMSSD (−1.52, −2.18 to −0.87), pNN50 (−1.36, −1.83 to −0.88), TP (−2.05, −2.87 to −1.24), HFnu (−3.51, −4.76 to −2.26), and VLF power (−2.65, −3.74 to −1.55), and an increase in LFnu (2.66, 1.55 to 3.78) and LF/HF ratio (1.75, 1.02 to 2.48) (p < 0.01). Most parameters had ES that was twice as high in overt compared to subclinical hyperthyroidism. Increased peripheral thyroid hormones and decreased TSH levels were associated with lower RR intervals. Conclusions: Hyperthyroidism is associated with a decreased HRV, which may be explained by the deleterious effect of thyroid hormones and TSH. The increased sympathetic and decreased parasympathetic activity may have clinical implications.