Exercise affects high-fat diet-stimulated breast cancer metastasis through irisin secretion by altering cancer stem cell properties.

Background: Regular physical activities reduce the growth of breast cancer, but research on the effects of steady exercise on metastasis and its mechanisms is limited. In this study, the effects of steady exercise on breast cancer metastasis and its possible mechanism were demonstrated. Methods: Experimental metastasis was induced after 8 weeks of steady exercise using a mouse model. Furthermore, one of the myokines, irisin, was studied to elucidate the effects of metastasis-regulating protein expression, and colony and sphere formation, which are cancer stem cell properties. Results: Low- and moderate-intensity exercise significantly reduced the number and volume of metastasized tumors. Among myokines, only irisin was significantly increased by steady exercise but decreased by a high-fat diet. In vitro studies, irisin significantly decreased the number of colonies and sphere formation. Irisin also inhibited cell migration and invasion and suppressed the malignancy of breast cancer cells by reducing the expression of vimentin, MMP-2, MMP-9, and HIF-1 and by increasing the expression of TIMP-1 and TIMP-2. Conclusion: Steady exercise modulates myokine secretions and among them, irisin suppresses breast cancer metastasis by decreasing self-renewal properties and invasion regulating protein expressions. Thus, regular exercise may be beneficial in the prevention of breast tumor metastasis.

Routine ophthalmologic examination in Klebsiella pneumoniae bacteremia is not necessary: incidence of and risk factors for ocular involvement.

Klebsiella pneumoniae bacteremia is known to present a virulent clinical course, including multiple metastatic infections, which is not uncommon in Asia. However, there are limited data on the incidence and risk factors for ocular involvement in K. pneumoniae bacteremia. We retrospectively reviewed the medical records of all patients with K. pneumoniae bacteremia who underwent ophthalmologic examination in a tertiary center in Seoul, Korea, from February 2012 to December 2020. Two retinal specialists reviewed the findings of the ophthalmologic examinations and classified them as endophthalmitis, chorioretinitis, and no ocular involvement. Of 689 patients, 56 [8.1%; 95% confidence interval (CI) 6.2-10.4] had ocular involvement, and 9 (1.3%; 95% CI 0.6-2.5) were diagnosed with endophthalmitis. Of 47 patients with chorioretinitis, 45 (95.7%) improved with systemic antibiotic therapy alone. Community-onset bacteremia (100% vs 62.1% vs 57.4%, P = 0.04), cryptogenic liver abscess (55.6% vs 11.8% vs 8.5%, P = 0.003), and metastatic infection (66.7% vs 5.8% vs 10.6%, P < 0.001) were more common in endophthalmitis than in no ocular involvement or chorioretinitis. In the multivariable analysis, cryptogenic liver abscess [adjusted odds ratio (aOR), 6.63; 95% CI 1.44-35.20] and metastatic infection (aOR, 17.52; 95% CI 3.69-96.93) were independent risk factors for endophthalmitis. Endophthalmitis was not associated with 30-day mortality. Endophthalmitis is rare in Asian patients with K. pneumoniae bacteremia. Targeted ophthalmologic examination in those with cryptogenic liver abscess, metastatic infection, or ocular symptoms may be more appropriate than routine examination of all patients.

Real-world study to evaluate the efficacy and safety of intravitreal brolucizumab for refractory neovascular age-related macular degeneration.

This retrospective study evaluated the real-world safety and effectiveness of switching to intravitreal brolucizumab for refractory neovascular age-related macular degeneration (nAMD). A total of 81 patients who received brolucizumab injections as switch therapy were followed for more than 3 months. A good response was defined as better anatomical improvement or extended injection intervals compared with previous anti-vascular endothelial growth factor (VEGF) treatment over a mean follow-up period of 41.4 weeks. Approximately 82.7% of patients showed a good response after switching. After 1 year, patients showed significant visual gains (+ 6.6 letters, p = 0.006) and central retinal thickness reductions (- 112.6 µm, p < 0.001), with 30.8% having injection intervals extended over 12 weeks. In the poor-response group, visual acuity and anatomical outcomes worsened soon after switching. More previous injections, thinner baseline central retina, and the presence of prechoroidal cleft or polypoidal lesion resulted in a better response (p < 0.05). Adverse effects occurred in eight eyes (9.9%), including one retinal vascular occlusion and seven intraocular inflammation cases, which were unrelated to the response. Most patients with nAMD refractory to anti-VEGF treatment demonstrated anatomical improvement or extended injection intervals after switching. This study shows that identified structural biomarkers may predict treatment response and select an appropriate therapeutic strategy.

MACULAR MICROVASCULATURE IN X-LINKED RETINOSCHISIS: Optical Coherence Tomography and Optical Coherence Tomography Angiography Study.

PURPOSE: The study aimed to evaluate the macular microvasculature of X-linked retinoschisis (XLRS) and identify correlations between vascular changes, structural changes, and functional outcome. METHODS: Genetically confirmed XLRS patients and heathy control subjects underwent complete ophthalmic examination, dilated funduscopic examination, optical coherence tomography, and optical coherence tomography angiography. Schisis distribution, outer plexiform layer discontinuation, photoreceptor layer thickness, and photoreceptor outer segment length were reviewed using optical coherence tomography. Vascular flow density and foveal thickness at foveal and parafoveal area were measured using optical coherence tomography angiography. RESULTS: A total of 17 eyes of 9 XLRS patients and 22 eyes of 11 control subjects were examined from July 2018 to August 2020. Flow density in the deep capillary plexus at foveal and parafoveal area decreased in XLRS patients compared with control subjects (P = 0.014 and 0.001, respectively), whereas foveal avascular zone area and perimeter remarkably increased (P = 0.015 and 0.001, respectively). Although outer and total retinal layers were significantly thicker in XLRS, inner retinal layer was thinner with reduced photoreceptor layer thickness and shortened photoreceptor outer segment length (P < 0.001 and P < 0.001, respectively). Foveal flow loss in deep capillary plexus, foveal avascular zone enlargement, thinner inner retina and photoreceptor layer thickness, and shortened photoreceptor outer segment length correlated with best-corrected visual acuity. CONCLUSION: X-linked retinoschisis eyes exhibit decreased flow density in the deep capillary plexus and variable foveal avascular zone with enlarged perimeter. Structural deterioration of the photoreceptor best reflects the degenerative changes, whereas microvascular alteration shows considerable correlation with functional outcome in XLRS.

Astigmatic correction of simultaneous femtosecond laser-assisted cataract surgery (FLACS) with intrastromal arcuate keratotomy (ISAK) versus Toric intraocular Lens Impantation with conventional phacoemulsification.

BACKGROUND: To compare the efficacies in astigmatic correction of simultaneous femtosecond laser-assisted cataract surgery (FLACS) with intrastromal arcuate keratotomy (ISAK) versus toric intraocular lens (IOL) implantation with conventional phacoemulsification in moderate astigmatism. METHODS: A retrospective chart review was conducted for patients who had undergone cataract surgery by one surgeon. We identified patients with preoperative corneal astigmatism from + 0.75 to + 2.00 diopters (D) who had undergone astigmatic correction with FLACS with ISAK or toric IOL implantation with conventional phacoemulsification. We measured the visual acuity, intraocular pressure, automated keratometer, manifest refraction, and topography preoperatively and 1-day, 1-month, 3-month, and 6-month postoperatively. The vector analysis of refractive astigmatism was performed. RESULTS: Of a total of 48 eyes of 48 patients, 27 eyes of 27 patients had FLACS with ISAK (AK group), and 21 eyes of 21 patients had conventional cataract surgery with toric IOL implantation (toric IOL group). Refractive astigmatism was significantly decreased in both groups. The mean preoperative and 6-month postoperative refractive astigmatism were 1.85 ± 1.07 and 0.99 ± 0.51 D, respectively, in the AK group (P = 0.028), and 1.84 ± 0.81 and 0.68 ± 0.21 D, respectively, in the toric IOL group (P < 0.001). There was no significant difference in refractive astigmatism between the two groups at 6-month postoperatively (0.99 ± 0.51 vs 0.68 ± 0.21 D, P = 0.057). At 6-month postoperatively, parameters for vector analysis of refractive astigmatism showed no statistical difference between the two groups. Corneal astigmatism was significantly decreased in the AK group. Corneal astigmatism from topography and the automated keratometer were significantly lower in the AK group 6-month postoperatively compared to toric IOL group (0.94 ± 0.40 vs. 1.53 ± 0.46 D, P = 0.018 for topography; and 0.98 ± 0.69 vs. 1.37 ± 0.41 D, P = 0.032 for the automated keratometer). CONCLUSIONS: FLACS with ISAK could be an effective procedure for reducing astigmatism as well as toric IOL implantation in cataract surgery.

Clinical Characteristics Associated with the Development of Cystoid Macular Edema in Patients with Cytomegalovirus Retinitis.

We evaluated the incidence and characteristics of eyes with cytomegalovirus (CMV) retinitis according to the occurrence of cystoid macular edema (CME) and identified the risk factors of its occurrence. Patients diagnosed with CMV retinitis and examined using optical coherence tomography were classified according to the development of CME. The CME group was further divided according to the presence of active retinitis at the time of CME development. The demographics, serologic findings, ophthalmic presentations, ocular treatments, and visual prognosis were compared. CME was identified in 25 eyes (17 eyes with active retinitis and 8 eyes with inactive retinitis) out of the 67 eyes with CMV retinitis. Visual acuity was worse in the CME group than in the non-CME group. The CME group had longer CMV viremia duration, zone 1 involvement, and larger extent of CMV retinitis. While CME with concurrent active retinitis developed in eyes with direct foveal involvement of retinitis in the acute phase and required more ganciclovir injections after CME development, CME without active retinitis developed in eyes with larger extents of involvement and more intravitreal ganciclovir injections before CME development. Zone 1 involvement and longer CMV viremia duration were independently associated with the occurrence of CME. CME, which caused visual deterioration, developed in considerable patients with CMV retinitis and had different characteristics according to the presence of active retinitis.

Effects of lid debris debridement combined with meibomian gland expression on the ocular surface MMP-9 levels and clinical outcomes in moderate and severe meibomian gland dysfunction.

BACKGROUND: To evaluate the effects of lid debris debridement and meibomian gland expression (MGX) on extracellular matrix metalloproteinase-9 (MMP-9) levels and clinical outcomes of moderate and severe MGD. METHODS: In this retrospective case series study, a total 48 eyes of 24 patients with moderate and severe MGD underwent one session of lid debris debridement using the BlephEx combined with MGX. We evaluated the tear film break-up time (TBUT), corneal and conjunctival fluorescein staining scores, Schirmer 1 test, biomicroscopic examination of lid margins and meibomian gland (MG), ocular surface disease index (OSDI) questionnaire score, and extracellular MMP-9 levels using a point-of-care MMP-9 immunoassay device before and 4 weeks after lid debris debridement and MGX. Linear mixed model and generalized estimating equations model were used to evaluate possible differences. RESULTS: There were significant improvements in the TBUT (P = 0.002), SICCA and Oxford staining scores (all P < 0.001), lid margin telangiectasia (P < 0.001 for upper and lower eyelids), lid thickness (P < 0.001 for upper and lower eyelids), MG orifice plugging (P < 0.001 for upper and lower eyelids), meibum color (P = 0.026 for upper eyelid, P < 0.001 for lower eyelid), meibum consistency (P < 0.001 for upper and lower eyelids), meibum grade (P < 0.001), MGD stage (P < 0.001), and OSDI score (P = 0.002). MMP-9 immunoassay positivity rate significantly decreased from 83.3 to 50.0% 4 weeks after treatment (P = 0.014). CONCLUSIONS: In patients with moderate to severe MGD, lid debris debridement using the BlephEx combined with MGX improved clinical findings, subjective symptoms, meibomian gland function, along with ocular surface MMP-9 level. We hereby suggest lid debris debridement using BlephEx combined with MGX as an effective clinical strategy for treatment of moderate to severe MGD.

Additive Role of Optical Coherence Tomography Angiography Vessel Density Measurements in Glaucoma Diagnoses.

PURPOSE: This study compared the glaucoma diagnostic abilities of optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). In addition, the possibility of enhancing diagnostic capability by combining the two modalities was investigated. METHODS: A total of 131 healthy eyes and 113 glaucomatous eyes were imaged by both OCT and OCTA. In OCT, glaucoma was defined as when the color of the superior or inferior quadrant of the peripapillary retinal nerve fiber layer thickness map was yellow (borderline, <5%) or red (outside normal limits, <1%). In OCTA, glaucoma was determined using the cut-off value of the superior or inferior peripapillary vessel density, calculated after receiver operating characteristic curve analysis. Sensitivity and specificity were determined by OCT alone, by OCTA alone, or by OCT and OCTA combined. RESULTS: The sensitivity of OCT (86.7%) was better than that of OCTA (74.3%), whereas the specificity of OCTA (87.0%) was better than that of OCT (67.9%). When these two modalities were combined, both sensitivity and specificity were enhanced (90.3% and 92.4%, respectively). Among the 131 eyes, 32 were misdiagnosed as glaucomatous by OCT but accurately diagnosed as normal by OCTA. These eyes were myopic, with a longer axial length and a thinner and temporally displaced peak of peripapillary retinal nerve fiber layer thickness, causing the false positive result in OCT. CONCLUSIONS: When OCTA was combined with OCT, the specificity of glaucoma diagnoses were enhanced. OCTA may compensate for the shortcomings of OCT in the diagnosis of glaucoma.