Two Cases of Atopic Dermatitis Patients With Scleral Perforation After Recurrent Scleritis Induced by Scleral-Sutured Posterior Chamber Intraocular Lens Implantation.

This report describes two cases of atopic dermatitis patients with scleral perforation after recurrent scleritis induced by suture exposure after scleral-sutured posterior chamber intraocular lens (PC-IOL) implantation. The first patient was a 41-year-old man (case 1), and the second was a 46-year-old man (case 2). Both had a history of atopic dermatitis and scleral-sutured intraocular lens (IOL) implantation. Scleritis recurred at the suture site after scleral-sutured IOL implantation in both patients. Although the scleritis was controlled by topical and/or systemic anti-inflammatory drugs, the sclera was perforated in both cases because of exposure of the suture knots (after seven years in case 1 and after 11 years in case 2). In case 1, the superotemporal IOL haptic was also exposed over the conjunctiva, and in case 2, the ciliary body was incarcerated in the scleral hole with deformation of the pupil superonasally. Considering that there were no signs of severe intraocular inflammation, surgical intervention was performed in both cases. In case 1, IOL repositioning was performed with oral prednisolone cover at a dosage of 15 mg/day, starting two weeks prior to the surgery. The steroid dosage was gradually tapered off until two months after the surgery. In case 2, the scleral patch underwent without IOL extraction, and no steroid or immunosuppression cover was administered. There was no recurrence of scleritis after surgery in either case, and visual acuity was preserved in both cases. The scleral perforation that occurred after scleral-sutured IOL implantation in these patients was thought to be the result of recurrent scleritis caused by suture exposure and chronic mechanical irritation by a suture knot. The scleritis subsided without removal of the IOL by moving the suture site of the IOL haptic and covering the suture with a scleral flap or patch graft.

Faricimab for Diabetic Macular Edema in Patients Refractory to Ranibizumab or Aflibercept.

Background and Objectives: Faricimab is the first intravitreal injection of vascular endothelial growth factor-A and angiopoietin-2 bispecific monoclonal antibody. Here, we evaluate the functional and anatomical outcomes of faricimab treatment in patients with diabetic macular edema (DME) that was refractory to ranibizumab or aflibercept. Materials and Methods: We performed a retrospective, observational, consecutive-case study of patients who had DME that was refractory to treatment with ranibizumab or aflibercept and were treated with faricimab between July 2022 and January 2023 under a pro re nata regimen. All the participants were followed for ≥4 months after the initiation of faricimab. The primary outcome was a recurrence interval of ≥12 weeks, and the secondary outcomes were the changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT). Results: We analyzed 18 eyes of 18 patients. The mean recurrence interval of previous anti-VEGF injection was 5.8 ± 2.5 weeks, which was significantly extended to 10.8 ± 4.9 weeks (p = 0.0005) by the switch to faricimab. Eight patients (44.4%) achieved a recurrence interval of ≥12 weeks. A history of subtenon injection of triamcinolone acetonide (p = 0.0034) and the presence of disorganization of the retinal inner layers (p = 0.0326) were found to be significantly associated with a recurrence interval of <12 weeks. The mean BCVAs were 0.23 ± 0.28 logMAR and 0.19 ± 0.23 logMAR, and the mean CMTs were 473.8 ± 222.0 µm and 381.3 ± 219.4 µm at baseline and 4 months, respectively, but these changes were not statistically significant. None of the patients experienced serious adverse events. Conclusions: Faricimab may extend the treatment interval for patients with DME that is refractory to ranibizumab or aflibercept. DME previously treated with the subtenon injection of triamcinolone acetonide or associated with disorganization of the retinal inner layers may be less likely to be associated with a longer recurrence interval after switching to faricimab.

Binary classification of users of electronic cigarettes and smokeless tobacco through biomarkers to assess similarity with current and former smokers: machine learning applied to the population assessment of tobacco and health study.

BACKGROUND: Exposure to harmful and potentially harmful constituents in cigarette smoke is a risk factor for cardiovascular and respiratory diseases. Tobacco products that could reduce exposure to these constituents have been developed. However, the long-term effects of their use on health remain unclear. The Population Assessment of Tobacco and Health (PATH) study is a population-based study examining the health effects of smoking and cigarette smoking habits in the U.S. POPULATION: Participants include users of tobacco products, including electronic cigarettes and smokeless tobacco. In this study, we attempted to evaluate the population-wide effects of these products, using machine learning techniques and data from the PATH study. METHODS: Biomarkers of exposure (BoE) and potential harm (BoPH) in cigarette smokers and former smokers in wave 1 of PATH were used to create binary classification machine-learning models that classified participants as either current (BoE: N = 102, BoPH: N = 428) or former smokers (BoE: N = 102, BoPH: N = 428). Data on the BoE and BoPH of users of electronic cigarettes (BoE: N = 210, BoPH: N = 258) and smokeless tobacco (BoE: N = 206, BoPH: N = 242) were input into the models to investigate whether these product users were classified as current or former smokers. The disease status of individuals classified as either current or former smokers was investigated. RESULTS: The classification models for BoE and BoPH both had high model accuracy. More than 60% of participants who used either one of electronic cigarettes or smokeless tobacco were classified as former smokers in the classification model for BoE. Fewer than 15% of current smokers and dual users were classified as former smokers. A similar trend was found in the classification model for BoPH. Compared with those classified as former smokers, a higher percentage of those classified as current smokers had cardiovascular disease (9.9-10.9% vs. 6.3-6.4%) and respiratory diseases (19.4-22.2% vs. 14.2-16.7%). CONCLUSIONS: Users of electronic cigarettes or smokeless tobacco are likely to be similar to former smokers in their biomarkers of exposure and potential harm. This suggests that using these products helps to reduce exposure to the harmful constituents of cigarettes, and they are potentially less harmful than conventional cigarettes.

DRAINAGE RETINOTOMY IS A RISK FACTOR FOR SURGICAL FAILURE AFTER PARS PLANA VITRECTOMY IN PATIENTS WITH PRIMARY UNCOMPLICATED RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To identify risk factors for recurrent retinal detachment after uncomplicated pars plana vitrectomy in patients with primary rhegmatogenous retinal detachment (RRD). METHODS: This single-center retrospective study included patients with primary RRD who underwent 23-gauge and 25-gauge pars plana vitrectomy at Hiroshima University Hospital between January 2016 and May 2021. All patients had ≥3 months of follow-up. Patients were excluded if they had preoperative proliferative vitreoretinopathy worse than Grade C1; giant retinal tears; tractional, exudative, or traumatic retinal detachment; or the use of perfluorocarbon liquid. Factors that influenced RRD treatment outcome and postoperative complications were evaluated. RESULTS: We analyzed 519 eyes of 509 patients who underwent pars plana vitrectomy for primary RRD. The primary and final success rates were 93.8% and 99.8%, respectively. Drainage retinotomy was a risk factor for surgical failure in both multivariate analysis (odds ratio 2.36, 95% confidence interval 1.08-5.15, P = 0.0314) and a propensity score-matching analysis (odds ratio 3.20, 95% confidence interval 1.14-9.04, P = 0.0277). Postoperative epiretinal membrane was associated with drainage retinotomy in multivariate analysis (odds ratio 1.93, 95% confidence interval 1.04-3.57, P = 0.0358). CONCLUSION: The avoidance of drainage retinotomy during small-gauge pars plana vitrectomy in patients with RRD may lead to better surgical success and less frequent epiretinal membrane formation.

Irreversible intraocular pressure elevation as a complication of MIRAgel scleral buckling.

Purpose: To report a case of ocular hypertension due to swelling and degeneration of hydrogel explant (MIRAgel) after retinal detachment surgery. Observations: The patient who had a history of left retinal detachment 23 years prior had been regularly followed up for epiretinal membrane in the left eye at the Department of Ophthalmology, Hiroshima University Hospital. Two years after the first presentation, the patient had symptoms of foreign body sensation and hyperemia, with elevation of the intraocular pressure (IOP) of the left eye to 24 mmHg. Two months later, the patient noticed omnidirectional oculomotor disturbances in the left eye, and magnetic resonance imaging (MRI) revealed swelling of the buckle material, presumably hydrogel explant, surrounding his left eye. His oculomotor disturbances worsened, and the left eye IOP remained high at 40 mmHg, despite the administration of antihypertensive eye drops. Subsequently, the swollen hydrogel explant was surgically removed. After the surgery, there was improvement of the diplopia and foreign body sensation. However, IOP in the left eye remained at 34 mmHg, and a trabeculectomy was performed to normalize the IOP. Conclusions and Importance: As far as we know, there have been no reported cases of irreversible ocular hypertension due to hydrogel explant. Stenosis of the trabecular outflow pathway secondary to compression of the superior scleral vein by long-term swollen hydrogel explant and inflammation around the hydrogel explant may be the cause of irreversible IOP elevation. Trabeculectomy may be effective for treating the intraocular hypertension caused by hydrogel explant.

Incidence of ocular inflammation among patients with active tuberculosis or nontuberculous mycobacterial infections in a tertiary hospital in Japan.

PURPOSE: This study aimed to elucidate the incidence of ocular involvement among patients with active tuberculosis (TB) or nontuberculous mycobacterial (NTM) infection in a hospital in Japan. METHODS: Patients with active TB or NTM infection at Yoshijima Hospital from April 2017 to July 2018 were included in this retrospective study. All patients underwent ophthalmic examinations, including fundus evaluation under pupil dilation, before initiation of antibiotic therapy. Patients with ocular inflammation were regularly followed up by ophthalmologists. RESULTS: In total, 101 patients with active TB and 27 patients with active NTM infection underwent ophthalmic examinations during the study period. Seven patients with TB (6.9%) had ocular inflammation; four had bilateral involvement. In these seven patients, ocular inflammation comprised anterior uveitis (n = 2), intermediate uveitis (n = 1), posterior uveitis (n = 4). Choroidal tubercles were observed in two patients with posterior uveitis. Female sex was associated with higher incidence of ocular inflammation among patients with TB. Conversely, no patients with NTM infection had ocular inflammation. CONCLUSION: Ocular inflammation was present in approximately 7% of patients with active TB. Although TB choroiditis is presumed to be rare in Japan, approximately 30% of the patients with ocular inflammation exhibited choroidal lesions in this study. In contrast, no ocular inflammation was observed among patients with systemic NTM infection.

Effects of reduced exposure to cigarette smoking on changes in biomarkers of potential harm in adult smokers: results of combined analysis of two clinical studies.

Purpose: Nonconventional vapor products (NVP), designed to reduce exposure to cigarette smoke toxicants (CSTs), could cause changes in biomarkers of potential harm (BoPH). Although, NVPs reduced CSTs exposure compared to conventional cigarettes (CC), the changes in the BoPH values varied among the studies. Hence, further information on BoPH using NVPs is needed. Material and methods: The data of two similarly designed studies using a kind of NVP, a noncombustion and nonheating inhaler type of smokeless tobacco product (NCIT) used under 31-day confinement, were pooled, and the differences in 15 BoPH between smokers and nonsmokers at baseline and between the 1 mg tar CC (CC1) group and NCIT group at Day 28/29 were analyzed. Results: At baseline, the levels of eight BoPH (red blood cells, white blood cells, 8-epi-prostaglandin F2α, 8-hydroxy-2'-deoxyguanosine, malondialdehyde, 11-dehydrothromboxane B2, total cholesterol and glucose) were significantly different between smokers and nonsmokers. At Day 28/29, the levels of six BoPH were significantly different between NCIT and CC1 (8-epi-prostaglandin F2α, malondialdehyde, 11-dehydrothromboxane B2: CC1 > NCIT, total bilirubin, low-density lipoprotein cholesterol and total cholesterol: CC1 < NCIT). Conclusions: Reduced exposure to CSTs has favorable effects on BoPH associated with oxidative stress, antioxidant capacity and platelet activation/coagulation but not in lipid metabolism.

Effects of exposure to male goat hair extracts on luteinizing hormone secretion and neuronal activation in seasonally anestrous ewes.

In sheep and goats, exposure of seasonally anestrous females to males or their fleece/hair activates the gonadotropin-releasing hormone (GnRH) pulse generator leading to pulsatile luteinizing hormone (LH) secretion. Pheromones emitted by sexually mature males are thought to play a prominent role in this male effect. In the present study, we first aimed to clarify whether the male goat pheromone is effective in ewes. Seasonally anestrous St. Croix ewes were exposed to hair extracts derived from either intact or castrated (control) male Shiba goats. The male goat-hair extract significantly increased LH secretion compared to the control, suggesting that an interspecies action of the male pheromone occurs between sheep and goats. Using the male goat-hair extract as the pheromone source, we then aimed to clarify the neural pathway involved in the signal transduction of the male pheromone. Ewes were exposed to either the goat-hair extract or the control and sacrificed 2 hr after the exposure. Expression of c-Fos, a marker of neuronal activation, was immunohistochemically examined. The male goat-hair extract significantly increased the c-Fos expression compared to the control in regions of the vomeronasal system, such as the accessory olfactory bulb and medial amygdala, and the arcuate nucleus. The main olfactory bulb did not exhibit any significant increase in the c-Fos expression by the male goat-hair extract. This result suggests that the neural signal of the male pheromone is conveyed to the GnRH pulse generator through the activated regions in ewes.

Existence of Gαi2-expressing axon terminals in the goat main olfactory bulb.

In rodents, Gα(i2)-expressing sensory neurons (SNs) that co-express vomeronasal receptor type 1 (V1R) are specifically found in the vomeronasal organ (VNO) and project their axons to the accessory olfactory bulb (AOB). In goats, however, Gα(i2)/V1R-expressing SNs exist in both the VNO and the olfactory epithelium. Thus, we examined whether the Gα(i2)-expressing axons functionally project to the main olfactory bulb (MOB). We analyzed the expression of Gα(i2) in the olfactory bulb and found small Gα(i2)-immunoreactive clusters in the MOB. The Gα(i2)-immunoreactive axons in these clusters made synaptic contacts with second-order neurons in the MOB. These results suggest that some Gα(i2)-expressing SNs functionally project their axons to the MOB in goats.

Conserved repertoire of orthologous vomeronasal type 1 receptor genes in ruminant species.

BACKGROUND: In mammals, pheromones play an important role in social and innate reproductive behavior within species. In rodents, vomeronasal receptor type 1 (V1R), which is specifically expressed in the vomeronasal organ, is thought to detect pheromones. The V1R gene repertoire differs dramatically between mammalian species, and the presence of species-specific V1R subfamilies in mouse and rat suggests that V1R plays a profound role in species-specific recognition of pheromones. In ruminants, however, the molecular mechanism(s) for pheromone perception is not well understood. Interestingly, goat male pheromone, which can induce out-of-season ovulation in anestrous females, causes the same pheromone response in sheep, and vice versa, suggesting that there may be mechanisms for detecting "inter-species" pheromones among ruminant species. RESULTS: We isolated 23 goat and 21 sheep intact V1R genes based on sequence similarity with 32 cow V1R genes in the cow genome database. We found that all of the goat and sheep V1R genes have orthologs in their cross-species counterparts among these three ruminant species and that the sequence identity of V1R orthologous pairs among these ruminants is much higher than that of mouse-rat V1R orthologous pairs. Furthermore, all goat V1Rs examined thus far are expressed not only in the vomeronasal organ but also in the main olfactory epithelium. CONCLUSION: Our results suggest that, compared with rodents, the repertoire of orthologous V1R genes is remarkably conserved among the ruminants cow, sheep and goat. We predict that these orthologous V1Rs can detect the same or closely related chemical compound(s) within each orthologous set/pair. Furthermore, all identified goat V1Rs are expressed in the vomeronasal organ and the main olfactory epithelium, suggesting that V1R-mediated ligand information can be detected and processed by both the main and accessory olfactory systems. The fact that ruminant and rodent V1Rs have distinct features suggests that ruminant and rodent V1Rs have evolved distinct functions.

Xenopus V1R vomeronasal receptor family is expressed in the main olfactory system.

To date, over 100 vomeronasal receptor type 1 (V1R) genes have been identified in rodents. V1R is specifically expressed in the rodent vomeronasal organ (VNO) and is thought to be responsible for pheromone reception. Recently, 21 putatively functional V1R genes were identified in the genome database of the amphibian Xenopus tropicalis. Amphibians are the first vertebrates to possess a VNO. In order to determine at which point during evolution the vertebrate V1R genes began to function in the vomeronasal system, we analyzed the expression of all putatively functional V1R genes in Xenopus olfactory organs. We found that V1R expression was not detected in the VNO but was specifically detected in the main olfactory epithelium (MOE). We also observed that V1R-expressing cells in the MOE coexpressed Gi2, thus suggesting that the V1R-Gi2-mediated signal transduction pathway, which is considered to play an important role in pheromone reception in the rodent VNO, exists in the amphibian MOE. These results suggest that V1R-mediated signal transduction pathway functions in Xenopus main olfactory system.

Central administration of neuropeptide B, but not prolactin-releasing peptide, stimulates cortisol secretion in sheep.

Two neuropeptides, neuropeptide B (NPB) and prolactin-releasing peptide (PrRP), have been suggested to play important roles in control of the hypothalamic-pituitary-adrenal (HPA) axis in rodents. The aim of the present study was to clarify the central actions of NPB or PrRP in sheep. Ovariectomized ewes were surgically implanted with a cannula directed to the lateral ventricle. They received intracerebroventricular (icv) administration of 400 mul of artificial cerebrospinal fluid, NPB (0.05, 0.5 or 5 nmol), PrRP (0.5, 5 or 50 nmol) or corticotropin-releasing hormone (CRH, 0.5 or 5 nmol) through the cannula, and blood samples were taken 30 and 0 min prior to and 15, 30, 60 and 90 min after the injection. Cortisol concentrations in plasma were determined by enzyme immunoassay. Administration of 0.5 nmol NPB resulted in a significant increase in the cortisol concentration compared with the vehicle control, whereas the cortisol concentration after lower or higher doses of NPB did not differ from the control value. Thus, an icv injection of NPB produced a bell-shaped dose-response of cortisol concentration. Administration of PrRP had no significant effect on the cortisol concentrations at any dose examined. Icv injection of CRH dose-dependently increased plasma cortisol concentrations. These results demonstrate that central NPB stimulates cortisol secretion, suggesting that this neuropeptide plays some roles in control of the HPA axis in sheep. On the other hand, unlike its role in rodents, PrRP is unlikely to be involved in control of the HPA axis in this species.