Topical tacrolimus for high-risk corneal transplantation: a randomized, clinical trial.

BACKGROUND: The prevalence of rejection is 10-30% in penetrating keratoplasty (PKP) case, and the rate is higher in cases of high-risk patients. Although using topical corticosteroids is a standard method for management the rejection of post-PKP patients, it may not be sufficiently potent in high-risk patients. Topical administration of tacrolimus (TAC) may be effective in suppression rejection after corneal transplantation. This study aimed to investigate the efficacy and safety of topical TAC in high-risk PKP patients in Japan. METHODS: This study was a single centre, single-blinded, randomized controlled trial. Patients with a history of PKP, graft rejection, atopic dermatitis, or deep corneal neovascularisation who underwent PKP were enrolled. They were randomly assigned to receive 0.1% TAC ophthalmic suspension or artificial tear (AT) up to week 52 after surgery. All participants received 0.1% betamethasone up to week 13 after surgery then they received 0.1% fluorometholone up to week 52. The incidence of immunological rejection during the observation period was the main outcome measure in this study. RESULTS: Thirty patients were enrolled in this study, and 12 eyes in the TAC group and 13 eyes in the AT group completed the study, respectively. Five out of 30 patients discontinued participation after providing informed consent. No serious adverse effects were developed in patients who received 0.1% TAC ophthalmic suspension. No rejection episodes occurred in the TAC group, while one eye in the AT group had rejection. Graft clarity, best spectacle-corrected visual acuity, intraocular pressure, and corneal endothelial cell density were not significantly different between the TAC and AT groups. CONCLUSION: Our results demonstrated that good tolerability of 0.1% TAC ophthalmic suspension. However, we failed to demonstrate its efficacy in preventing immunological rejection in high-risk patients undergoing PKP. TRIAL REGISTRATION: This study was first registered in the University Hospital Medical Information Network (UMIN000029669, Date of registration: November 1, 2017). With the enforcement of the Clinical Trial Act in Japan, the study re-registered in the Japan Registry of Clinical Trials (jRCTs031180342, Date of registration: March 18, 2019).

IMPACT OF GAS/AIR TAMPONADE ON REFRACTIVE OUTCOMES AFTER FLANGED INTRASCLERAL INTRAOCULAR LENS FIXATION.

PURPOSE: This study aims to investigate the postoperative refractive outcomes in eyes that underwent the flanged intrascleral intraocular lens (IOL) fixation combined with vitrectomy with or without gas/air tamponade. METHODS: The eyes were divided into two groups (Group A; eyes that underwent flanged intrascleral IOL fixation with gas/air tamponade, and Group B; eyes that underwent flanged intrascleral IOL fixation without gas/air tamponade). The predicted spherical equivalent (SE) refraction values were calculated using the Sander-Retzlaff-Kraff Theoretical formula. Then, the prediction error was calculated by subtracting the predicted SE refraction from the postoperative objective SE refraction and the absolute prediction error was calculated as the absolute value of the prediction error for each eye. RESULTS: A total of 68 eyes were included in the current study. There was a significant correlation between the predicted and postoperative SE refraction in both groups (Group A, r = 0.968, P < 0.0001, Group B, r = 0.943, P < 0.0001, linear regression analysis). The prediction error demonstrated a mild myopic shift after the flanged intrascleral IOL fixation in both groups (Group A, -0.40 ± 0.96 diopter, Group B, -0.59 ± 0.95 diopter). There was no significant difference in prediction error and absolute prediction error between the two groups ( P = 0.44, P = 0.70, Wilcoxon rank sum test). CONCLUSION: The postoperative SE refraction after flanged intrascleral IOL fixation was not influenced by gas/air tamponade.

Naldemedine-induced opioid withdrawal with restlessness as the predominant symptom in a palliative care setting.

OBJECTIVES: Opioid analgesics play a central role in cancer pain treatment; however, it has been reported that opioid-induced constipation (OIC) develops in 80% of patients using opioid analgesics and leads to a decrease in quality of life. Naldemedine improves constipation without affecting the analgesic action of opioid analgesics via peripheral µ-opioid receptors. METHODS: We report a terminally ill cancer patient who was diagnosed with opioid withdrawal syndrome (OWS) based on symptoms centered around restlessness and sweating that developed 43 days after administration of naldemedine for OIC. RESULTS: The patient was a 78-year-old woman who was diagnosed with stage IVB uterine sarcoma in October, 1 year prior to her visit to our clinic,  and underwent chemotherapy after surgery, but the disease became progressive. Thereafter, metastasis to the fourth thoracic vertebrae (Th4) was identified, and loxoprofen and acetaminophen were started for pain at the metastatic site. Oxycodone hydrochloride hydrate 10 mg/day was additionally administered on postoperative day 11, followed by naldemedine 0.2 mg/day for OIC. On the 43rd day after administration, the patient began to wander the hospital ward in a wheelchair and became noticeably restless. OWS due to naldemedine administration was suspected, and naldemedine was discontinued. The symptoms improved 7 days later, and no similar symptoms were observed thereafter. SIGNIFICANCE OF RESULTS: Patients receiving palliative care often exhibit psychiatric symptoms such as anxiety and depression, but OWS due to naldemedine should also be considered as a potential cause.

Bilateral corneal perforation caused by neurotrophic keratopathy associated with leprosy: a case report.

BACKGROUND: Neurotrophic keratopathy (NK) is a rare degenerative corneal disease caused by damage to the trigeminal nerve. We hereby describe a severe case with bilateral corneal perforation due to leprosy (Hansen's disease)-associated NK. CASE PRESENTATION: An 89-year-old man with a history of leprosy treated 40 years previously in our sanatorium developed bilateral corneal perforation due to NK. He had a history of bilateral persistent epithelial defects and bacterial keratitis. Although epithelialization was obtained with the use of autologous serum eye drops, progressive corneal thinning concomitant with stromalysis led to bilateral perforation. Over one month treatment with topical antibiotics, anti-inflammatory and lubricants resulted in healing of the epithelial defects and corneal perforations. A Cochet-Bonnet esthesiometer demonstrated a total absence of corneal sensation in both eyes. CONCLUSIONS: The present case indicated the irreversible nerve damage due to leprosy that had been cured 23 years ago, which can progress over the years and cause bilateral corneal perforations.

Point Prevalence Surveys of Antimicrobial Prescribing in a Non-Acute Care Hospital in Saitama Prefecture, Japan.

Background: The global point prevalence survey (Global-PPS) is the standard for the surveillance of prescribed antimicrobials among inpatients and provides data for the development of hospital antimicrobial stewardship programs. Aim: To evaluate the prevalence and quality of antimicrobial prescriptions using the universally standardized Global-PPS protocol in a non-acute care hospital in Saitama Prefecture, Japan. Methods: Antimicrobial prescriptions for inpatients, staying at the hospital overnight, were surveyed on three separate week days in November 2018, January 2019, and May 2019. Information on the prescribed antimicrobials on the survey target day was obtained from the in-hospital pharmacy. Survey data were collected by physicians, based on the extracted information. Patient information was anonymized and entered in the Global-PPS Web application by physicians. We report the antimicrobial use prevalence, the indication for prescription, diagnosis, the most prescribed antimicrobials, and a set of quality indicators related to antimicrobial prescribing. Results: In total, 6.7% of the surveyed inpatients (120/1796) were prescribed antimicrobials on the survey day. Sulfamethoxazole/trimethoprim was the most commonly prescribed, with 20.0% of systemic antibiotic prescriptions (ATC J01). Of all antibiotics for systemic use, up to 58.4% were Watch antibiotics, as defined by the World Health Organization AWaRe classification. The most prescribed group of systemic antibiotics was non-penicillin beta-lactam antibiotics (34.4%), followed by penicillin antibiotics in combination with beta-lactamase inhibitors (25.6%), and sulfonamides with trimethoprim (20.8%). Healthcare-associated infections and medical prophylaxis were the most common indications reported in 69.3% and 26.3% of prescriptions, respectively. The most common diagnosis for systemic antibiotic prescriptions was pneumonia (49.6%). Reasons for antimicrobial prescriptions were indicated in the medical records for 67.1% of prescriptions, and the stop/review date was documented to be 50.3%. Compliance with local guidelines reached 66.7%. Conclusions: This study highlights important challenges related to antimicrobial prescription in a highly specific, non-acute care patient population.

Elevated Cytokine Levels in Aqueous Humor Are Associated with Peripheral Anterior Synechiae after Penetrating Keratoplasty.

Peripheral anterior synechiae (PAS) after corneal transplantation leads to refractory glaucoma and permanent loss of vision. However, the exact mechanism remains elusive. This study aimed to evaluate the association between cytokine levels in the aqueous humor (AqH) and the progression of PAS after penetrating keratoplasty (PKP). We measured 20 cytokine levels in AqH and assessed the correlation with PAS progression after PKP in 85 consecutive patients who underwent PKP. We also evaluated age-dependent alterations in PAS and cytokine levels in DBA2J mice. PAS developed in 38 (44.7%) of 85 eyes after PKP. The incidence of intraocular pressure increase after PKP was significantly greater in eyes with PAS (26.3%) than in those without PAS (2%, p = 0.0009). The PAS area at 12 months after PKP was significantly positively correlated with the preoperative levels of interleukin (IL)-6, interferon (IFN)-γ and monocyte chemotactic protein (MCP)-1 (p ≤ 0.049). In the DBA2J mice, an experimental glaucoma model that developed PAS at 50 weeks, the AqH levels of IL-2, IL-6, IL-10, IFN-γ, tumor necrosis factor-α, MCP-1 and granulocyte-macrophage colony-stimulating factor (GM-CSF) significantly increased at 50 weeks compared to 8 weeks (p ≤ 0.021). In conclusion, inflammatory alterations in the AqH microenvironment, such as high preoperative specific cytokine levels, can lead to PAS formation and glaucoma.

Corneal Higher-Order Aberrations in Eyes With Corneal Scar After Traumatic Perforation.

OBJECTIVES: To evaluate corneal higher-order aberrations (HOAs) in eyes with corneal scar after traumatic perforation and their correlation with visual acuity. METHODS: This retrospective consecutive case study included 40 eyes of 40 consecutive patients (mean age, 39.2±21.6 years), treated for traumatic corneal perforation at Tokyo Dental College, and 18 normal control eyes. Higher-order aberrations of anterior and posterior corneal surfaces and total cornea were analyzed by swept-source optical coherence tomography. Correlations between corneal HOAs and visual acuity were analyzed. RESULTS: Higher-order aberrations within 4-mm diameter were significantly larger in eyes with corneal perforation (anterior surface, 0.51±0.54 µm; posterior surface, 0.20±0.14; and total cornea, 0.52±0.50) as compared to normal controls (0.10±0.02, 0.02±0.01, and 0.09±0.02, respectively; all P<0.001). Higher-order aberrations within 6-mm diameter were significantly larger in eyes with corneal perforation (anterior surface, 1.15±1.31; posterior surface, 0.31±0.23; and total cornea, 1.09±1.28) as compared to normal controls (0.21±0.06, 0.06±0.01, and 0.19±0.06, respectively; all P<0.001). The most common topography pattern observed was the minimal change pattern (37.5%), followed by asymmetric pattern (30.0%). Visual acuity significantly correlated with corneal HOAs (anterior surface: R=0.646, P<0.001; posterior surface: R=0.400, P=0.033; and total cornea: R=0.614, P<0.001). CONCLUSIONS: Corneal scar after traumatic perforations not only induces corneal opacity, but also increases corneal HOAs, which indicates a direct effect on visual acuity.

Impact of Corneal Higher-Order Aberrations on Visual Acuity After Deep Anterior Lamellar Keratoplasty in Treating Keratoconus.

PURPOSE: To evaluate the incidence of the Descemet membrane (DM) folds after deep anterior lamellar keratoplasty (DALK) in treating keratoconus. We also evaluated the influence of DM folds and corneal higher-order aberrations (HOAs) on visual acuity after DALK. METHODS: This retrospective study included 89 consecutive eyes of 87 patients who underwent DALK for the treatment of keratoconus at Tokyo Dental College Ichikawa General Hospital from April 2002 to June 2017. The presence or absence of DM folds was determined by slitlamp microscopy. Visual acuity after DALK was compared between the eyes with and without DM folds. Corneal HOAs of the anterior and posterior surfaces and the total cornea were measured by anterior segment optical coherence tomography. Correlations among the presence of DM folds, corneal HOAs, and visual acuity were analyzed. RESULTS: The Descemet membrane folds developed in 28.1% (25/89) eyes after DALK for the treatment of keratoconus. However, there were no significant differences in postoperative visual acuity between the eyes with and without DM folds at 1, 3, 6, and 12 months (P=0.739, P=0.106, P=0.223, and P=0.186, respectively). The visual acuity at 12 months was significantly correlated with corneal HOAs within a 4-mm diameter (anterior surface: R=0.546, P=0.003; total cornea: R=0.506, P=0.007). CONCLUSIONS: Larger corneal HOAs, but not the presence of DM folds, were associated with poor visual acuity after DALK. In treating advanced keratoconus with DALK, it is important to minimize postoperative corneal HOAs, although DALK improves visual acuity by reducing HOAs due to keratoconus.

Elevation of preoperative recipient aqueous cytokine levels in eyes with primary graft failure after corneal transplantation.

Purpose: Primary graft failure after corneal transplantation is caused by dysfunction of corneal endothelial cells. Recently, we demonstrated that preoperative recipients' aqueous cytokine levels are associated with rapid corneal endothelial cell loss after corneal transplantation. In the present study, we evaluated the preoperative inflammatory cytokine levels in the aqueous humor (AqH) of eyes with primary graft failure following corneal transplantation. Methods: Among the prospective consecutive case series (273 eyes), this study included patients who developed primary graft failure (eight eyes) and patients who underwent corneal transplantation for the treatment of bullous keratopathy (108 eyes) or cataract surgery (30 eyes). AqH samples were collected at the beginning of each surgery. The levels of the cytokines (interleukin [IL]-4, IL-6, IL-8, IL-10, IL-12p70, IL-17A, interferon [IFN]-γ, monocyte chemotactic protein [MCP]-1, E-selectin, P-selectin, and soluble intercellular adhesion molecule [sICAM]-1) in the AqH were measured with multiplex beads immunoassay. Results: In eyes with primary graft failure, the preoperative levels of aqueous protein (4.6-fold), interleukin (IL)-6 (179-fold), IL-17A (7.1-fold), MCP-1 (2.6-fold), IFN-γ (4.3-fold), E-selectin (2.3-fold), P-selectin (2.0-fold), and sICAM-1 (5.5-fold) were statistically significantly higher compared to the cataract controls (p<0.0021). There was no primary graft failure among the recipients who received corneal grafts of fellow eyes from the same donors. Conclusions: Preoperative levels of AqH cytokines, such as IL-6, IL-17A, MCP-1, IFN-γ, and sICAM-1, increased in eyes with primary graft failure after corneal transplantation. These cytokine levels could be prognostic biomarkers to predict primary graft failure after corneal transplantation.

Decreased Visual Acuity by an Irregular Corneal Posterior Surface After Repeat Descemet Stripping Automated Endothelial Keratoplasty.

PURPOSE: To investigate the impact of higher-order aberrations (HOAs) on visual acuity after repeat Descemet stripping automated endothelial keratoplasty (DSAEK) in the same eyes. METHODS: This retrospective comparative case series includes 23 patients who underwent DSAEK twice in the same eyes (46 DSAEK in total). We evaluated the HOAs of the anterior and posterior corneal surfaces, and total cornea using the Fourier analysis data from anterior segment optical coherence tomography. Eyes were divided into one of the following groups, based on the improvement and decline in the best-corrected visual acuity (BCVA) after repeat DSAEK; group A: 12 eyes with an improvement ≥ 2 lines, group B: 12 eyes with a decline ≤ 2 lines, and group C: 11 eyes with no change or change within 1 line. RESULTS: The HOAs of the posterior surface in group B were significantly greater than those of group A (P=0.028), whereas there were no significant differences in the anterior surface and total corneal HOAs between groups A and B (P=0.12 and 0.08). There were no significant differences in the anterior and posterior surface as well as total cornea HOAs between initial DSAEK and repeat DSAEK in group C (P=0.87, 0.65, and 0.42). The postoperative BCVA had a significant correlation with the HOAs of the anterior and posterior surfaces as well as the total cornea (R=0.40, 0.46, and 0.53; P=0.01, 0.002, and 0.001). CONCLUSIONS: Posterior corneal HOAs can have a negative influence on the visual acuity after endothelial keratoplasty.