Novel rapid method for identifying and quantifying pathogenic bacteria within four hours of blood collection.

Sepsis is life-threatening organ dysfunction and is considered a major cause of health loss. However, since the current biomarkers of sepsis reflect the host's immune response to microorganisms, they would inevitably cause a time-lag. This means that there is still no truly reliable biomarker of sepsis. In the present study, we developed a novel method for identifying and quantifying unknown pathogenic bacteria within four hours of sample collection. The most important point of this study is that the novel method can be used to determine the number of bacteria in a sample as a novel biomarker of infectious diseases. Indeed, based on the number of bacteria, we were able to accurately estimate the severity of microbial infection. Furthermore, using the time-dependent changes in the number of bacteria, we were able to monitor the therapeutic effect accurately. The rapid identification and quantification of bacteria may change our approach to medical care.

Parameters of a basic ophthalmic examination that can ensure proper timing of corneal crosslinking in patients with keratoconus.

BACKGROUND: By the time patients with keratoconus are referred to specialists for treatment, the disease-related thinning of their corneas has already made them ineligible (< 400 µm) for corneal crosslinking (CXL). PURPOSE: To find basic ophthalmic examination parameters that can ensure proper timing of referral for CXL. METHODS: We reviewed cases referred to Toyama University Hospital for the treatment of keratoconus from August 2011 to May 2021 to identify the frequency of contraindication due to minimal corneal thickness (MCT) < 400 µm at first visit. We performed a receiver operator characteristic (ROC) analysis of basic exam parameters (uncorrected distance visual acuity, corrected distance visual acuity, corrected distance visual acuity with hard contact lens, sphericity, cylindricity, and/or corneal astigmatism) potentially predicting eligibility for CXL. For those with an area under the curve (AUC) > 0.8, we determined cut-off values and calculated sensitivity and specificity. RESULTS: Analyses included 66 eyes of 38 Japanese patients aged 25.0 ± 7.1 yrs (range 12-38 yrs) (56 male eyes and 10 female eyes). Thirty percent of the patients had an MCT < 400 µm. The AUC for uncorrected distance visual acuity (UCDVA) was 0.85. A cut-off value of 1.22 (converted to decimal visual acuity: ≥ 0.06) yielded 87% sensitivity and 75% specificity. The AUC for corrected distance visual acuity (CDVA) was 0.90. A cut-off of 0.52 (converted to decimal visual acuity: ≥ 0.3) yielded 89% sensitivity and 75% specificity. CONCLUSIONS: It is advisable to refer patients with keratoconus to a specialized facility for CXL when either of the following conditions is present: (i) UCDVA (decimal visual acuity) ≥ 0.06 or (ii) CDVA (decimal visual acuity) ≥ 0.3.

Improvement of the loss of corneal endothelial cells by relocating the tip of the Baerveldt® implant tube from the anterior chamber to the vitreous cavity.

PURPOSE: It has been reported that corneal endothelial cells (CEC) decrease faster when the tip of the Baerveldt glaucoma implant (BGI) tube is inserted into the anterior chamber than into the vitreous cavity. We investigated whether surgically relocating the tip of the BGI tube from the anterior chamber to the vitreous cavity could reduce CEC loss. PATIENTS AND METHODS: This was a single facility retrospective cohort study. The inclusion criteria were the CEC density less than 1500 cells/mm2 and the CEC reduction ratio was greater than 10%/year. The subjects were 11 consecutive patients that could be followed > 12 months after relocation surgery. All patients were undergone vitrectomy, and the tip of tube was inserted into the vitreous cavity from the anterior chamber. We compared the intraocular pressure (IOP), reduction slope of CEC density and annual reduction rate of CEC density before and after relocation surgery. We calculated the annual reduction ratio in comparison with the preoperative CEC density (%/year). RESULTS: The mean of period between the Baeveldt with anterior chamber insertion surgery and the relocation surgery was 33.8 ± 15.0 months. The mean of follow-up after relocation surgery was 21.8 ± 9.8 months. The relocation surgery did not significantly change IOP (p = 0.974). The mean preoperative and postoperative IOP were 13.1 ± 4.5 and 13.6 ± 4.3 mmHg. The reduction ratio of the CEC density was 15.4 ± 6.7 (%/year) before relocation surgery and significantly slower at 8.3 ± 6.5 (%/year) after relocation surgery (p = 0.024). Two patients resulted in bullous keratopathy after relocation surgery. CONCLUSIONS: Relocating the tip of BGI tube from the anterior chamber to the vitreous cavity could reduce CEC loss.

Histological Equivalence of a Hyper-Dry Amniotic Membrane and the Ambio2TM after Implantation in the Rabbit Conjunctiva.

PURPOSE: A hyper-dry amniotic membrane (HDAM) has been used clinically for ocular surface reconstruction, but sufficient evidence of the histological dynamics and long-term safety have not been obtained. We examined the histological changes in an HDAM after its subconjunctival implantation in rabbit eyes, and we compared these changes to those in the Ambio2TM Amniotic Membrane Graft (IOP Ophthalmics, Costa Mesa, CA, USA) after the same surgery. DESIGN: A prospective controlled animal study. METHODS: We used 27 rabbits in two groups: the HDAM group (36 eyes of 18 rabbits) and the Ambio2 group (18 eyes of 9 rabbits). The HDAM or Ambio2 was transplanted on the bare sclera and covered with a conjunctival autograft. The histological changes were determined by evaluating the amniotic membrane graft, inflammatory cells, and foreign body granulomas in hematoxylin/eosin-stained sections at 30 days, 93 days, and 184 days postoperatively. RESULTS: In all cases, the amniotic membrane graft was completely absorbed without scarring at 184 days postoperatively. The positive rate of inflammatory cells was significantly higher in the HDAM group compared to the Ambio2 group at 30 days postoperatively. The positive rate of foreign body granulomas decreased with time, with no significant difference between the two groups. CONCLUSIONS: Both the HDAM and Ambio2 were completely absorbed without scarring within 6 months after surgery. The two types of membranes showed histologically equivalent responses. Translational Relevance: Since the HDAM was completely absorbed without scarring within 6 months after surgery, we could confirm its long-term safety.

Clinicopathological features of considerable reduction in androgen receptor expression in sebaceous gland carcinoma of the eyelid.

PURPOSE: This study aimed to evaluate the relationships between androgen receptor (AR) expression and clinicopathologic features of sebaceous gland carcinoma (SGC) of the eyelid. METHODS: AR expression was evaluated via immunohistochemistry analysis of surgically derived samples from 11 patients with SGC of the eyelid. RESULTS: The expression of AR was evident in 9 of 11 patients (82%). We divided patients into high AR (7 patients) and low AR (4 patients: 2 patients with low expression and 2 patients with no expression) groups. The low AR group showed significantly greater progression than the high AR group with regard to T category and exhibited a lower grade of differentiation. CONCLUSION: In patients with SGC of the eyelid, a marked decrease in AR expression may be associated with a poor prognosis. AR may be a prognostic factor and a potential therapeutic target in cases of SGC of the eyelid.

Retinal Endovascular Surgery with Tissue Plasminogen Activator Injection for Central Retinal Artery Occlusion.

PURPOSE: To report 2 cases of central retinal artery occlusion (CRAO) who underwent retinal endovascular surgery with injection of tissue plasminogen activator (tPA) into the retinal artery and showed a remarkable improvement in visual acuity and retinal circulation. METHODS: Standard 25-G vitrectomy was performed under local anesthesia. Simultaneously, tPA (80,000 units/mL) solution was injected into the retinal artery of the optic disc for 2-3 min using a microneedle. Changes in visual acuity, fundus photography, optical coherence tomography (OCT), fluorescein angiography, and laser speckle flowgraphy (LSFG) results were examined. RESULTS: Both cases could be treated within 12 h after the onset of CRAO. Case 1 was a 47-year-old woman. Her visual acuity improved from counting fingers before operation to 0.08 logMAR 1 month after the surgery. However, thinning of the retina at the macula was observed by OCT. Case 2 was a 70-year-old man. His visual acuity improved from counting fingers to 0.1 logMAR 2 months after the surgery. Both fluorescein angiography and LSFG showed improvement in retinal circulation after the surgery in case 2. CONCLUSIONS: Retinal endovascular surgery with injection of tPA into the retinal artery was feasible and may be a way to improve visual acuity and retinal circulation when performed in the acute phase of CRAO.

Fluctuations of the Intraocular Pressure in Pseudoexfoliation Syndrome and Normal Eyes Measured by a Contact Lens Sensor.

PURPOSE: We compared the fluctuation of the intraocular pressure (IOP) in patients with pseudoexfoliation syndrome (PE) and individuals with normal healthy eyes. We measured continuous IOP using a SENSIMED Triggerfish contact lens sensor (CLS). METHODS: Eleven eyes with PE and 11 healthy eyes were examined. In all 22 participants, the IOP fluctuation was measured continuously for 24 hours with a CLS. The CLS could measure every 5 minutes. We evaluated IOP fluctuations over the 24-hour period separately for diurnal IOP and nocturnal IOP. We also identified each participant's maximum value. Changes in the corneal thickness and the corneal curvature were measured before and after the CLS use with anterior-segment optical coherence tomography. RESULTS: The mean IOP within the PE eyes was 20.3±3.9 mm Hg and that in the healthy eyes was 13.1±2.1 mm Hg (P<0.001). The 24-hour range of IOP fluctuations in the PE group was significantly larger than that in the healthy group (P=0.004). The central corneal thickness was significantly thicker after CLS use (P=0.011). The steeper meridian changed slightly to myopia (P=0.0068). All healthy eyes had their maximum value during the nocturnal period, whereas 7 of the 11 PE eyes (64%) had their maximum value in the nocturnal period. CONCLUSIONS: The IOP fluctuation was larger in the eyes with PE than in the healthy eyes. This larger fluctuation might be one of the reasons underlying the aggravation of the visual field by PE. Measurements of 24-hour continuous IOP might be useful to evaluate IOP fluctuation.

Corneal decompensation following filtering surgery with the Ex-PRESS(®) mini glaucoma shunt device.

PURPOSE: To report a case of corneal decompensation due to the Ex-PRESS(®) mini glaucoma shunt device (Ex-PRESS). PATIENT AND METHODS: A 75-year-old man had pseudoexfoliation glaucoma in his right eye. He underwent filtration surgery with Ex-PRESS. His intraocular pressure was 7 mmHg after 9 months. RESULTS: We observed partial decompensation of the corneal endothelium adjacent to the filtering bleb. Specular microscopy revealed a marked decrease in the endothelial cell density at the center of the cornea. CONCLUSION: Anterior segment optical coherence tomography is very useful for evaluating corneal edema and the position of Ex-PRESS. It is important to follow up with an examination of the corneal endothelial cells.

Improvement of fluctuations of intraocular pressure after cataract surgery in primary angle closure glaucoma patients.

BACKGROUND: Cataract surgery has been shown to reduce intraocular pressure (IOP) in eyes with primary angle closure glaucoma (PACG). In this study, we examined IOP fluctuations and circadian IOP patterns before and after cataract surgery in PACG patients using the contact lens sensor (CLS) Triggerfish. METHODS: This was a prospective open-label study. Ten consecutive patients with PACG were included. The patients underwent phacoemulsification and intraocular lens implantation (PEA+IOL) surgery. In each eye, IOP fluctuations over 24 h were measured with the CLS before and at three months after the surgery. Changes in corneal curvatures and anatomic parameters of the anterior chamber were measured by anterior segment optical coherence tomography (AS-OCT). RESULTS: The mean IOP was significantly reduced from 14.7 ± 1.5 mmHg to 11.2 ± 2.2 mmHg at three months after the surgery in PACG patients (P = 0.002). Although the mean range of 24-h IOP fluctuations was not significantly changed after the surgery (P = 0.49), the mean range of IOP fluctuations during the nocturnal period was significantly decreased from 246 ± 61 mVeq to 179 ± 64 mVeq after the surgery (P = 0.02). After the surgery, seven eyes of the ten (70%) showed the same circadian IOP patterns. AS-OCT showed significant improvements in the anatomic parameters of the anterior chamber after the surgery. CONCLUSIONS: Cataract surgery decreased IOP fluctuations during the nocturnal period in PACG patients. These effects might partly prevent the progression of PACG.

Efficacy of Intraoperative Anterior Segment Optical Coherence Tomography during Descemet's Stripping Automated Endothelial Keratoplasty.

Purpose. To examine the graft-host interface during Descemet's stripping automated endothelial keratoplasty (DSAEK) surgery with optical coherence tomography (OCT). Design. Prospective, interventional case series. Patients and Methods. Eight patients who underwent a DSAEK were included. A handheld OCT was used intraoperatively to examine the presence of interface fluid between the host cornea and the graft. Results. In 3 patients, no interface fluid was detected between the host cornea and the graft after the graft was attached by air injection. In 4 patients, interface fluid was detected after the graft was attached by air injection. The remaining interface fluid was drained through corneal stab incisions. One patient required a second surgery because the first surgery failed due to persistence of the interface fluid. All patients showed a complete attachment of the graft at one month after the DSAEK surgery. Conclusion. A handheld OCT is useful to detect the interface fluid between the host cornea and the graft during a DSAEK.

Comparison of fluctuations of intraocular pressure before and after selective laser trabeculoplasty in normal-tension glaucoma patients.

PURPOSE: The aim of this study was to examine the effects of selective laser trabeculoplasty (SLT) treatment on habitual intraocular pressure (IOP) fluctuations in patients with normal-tension glaucoma (NTG) using a SENSIMED Triggerfish contact lens sensor (CLS). MATERIALS AND METHODS: Ten patients diagnosed with NTG were enrolled in this study. All patients underwent SLT treatment. Habitual 24-hour IOP fluctuations were recorded before and after SLT. The IOP fluctuations were divided into diurnal periods and nocturnal periods and compared before and after SLT. Changes in corneal thickness and curvature were measured before and after the CLS use with anterior segment optical coherence tomography. RESULTS: The mean IOP was 13.5±2.5 mm Hg before SLT. The mean IOP at 1, 2, and 3 months after SLT was significantly decreased to 10.1±2.3 mm Hg (P=0.002), 11.2±2.7 mm Hg (P=0.0059), and 11.3±2.4 mm Hg (P=0.018), respectively. The range of IOP fluctuations over 24 hours was not significantly changed between before and after SLT treatment (P=0.77). Although the range of IOP fluctuations during the diurnal periods was not significantly changed between before and after SLT treatment (P=0.92), the range of IOP fluctuations during the nocturnal periods significantly decreased from 290±86 mVEq before SLT to 199±31 mVEq after SLT treatment (P=0.014). With respect to corneal changes, the steeper meridian decreased significantly after the CLS use (P=0.016), although other parameters showed no significant difference between before and after the CLS use. CONCLUSIONS: SLT treatment was shown to significantly lower IOP and decrease IOP fluctuations during the nocturnal periods in NTG patients. These effects might be important to prevent the progression of NTG.

Varicella-zoster virus keratitis with asymptomatic conjunctival viral shedding in the contralateral eye.

PURPOSE: To report a case of varicella-zoster virus (VZV) keratitis with detection of VZV DNA in the tear fluid of not only the symptomatic eye but also the contralateral asymptomatic eye by polymerase chain reaction (PCR). METHODS: This is a case report. A 63-year-old otherwise healthy woman presented with circular corneal ulcer and stromal opacity with infiltration accompanied by mild conjunctival and ciliary injections in the left eye. Bacterial cultures of the corneal scrapings and virus PCR analyses of tear fluid from both eyes were performed. RESULTS: No pathogen was found by bacterial cultures. PCR was negative for Acanthamoeba, herpes simplex virus and cytomegalovirus, but positive for VZV. VZV DNA was also detected in the unaffected eye. Based on the diagnosis of VZV keratitis, oral valacyclovir and acyclovir eye ointment were administered to the corneal infected eye. The infected eye was healed and VZV DNA turned negative in the tear fluid of the treated eye after 6 months of treatment; however, VZV DNA was still positive in the tear fluid of the contralateral eye. CONCLUSIONS: To our knowledge, this is the first case report of the detection of VZV DNA in the tear fluid of both affected and unaffected eyes in a patient with VZV keratitis. Asymptomatic conjunctival shedding of VZV may continue in the healthy unaffected eye in VZV keratitis patients.

Near-infrared fundus autofluorescence-visualized melanin in the choroidal abnormalities of neurofibromatosis type 1.

PURPOSE: To report a series of three cases of neurofibromatosis type 1 examined by near-infrared fundus autofluorescence (NIR-AF) with a scanning laser ophthalmoscope and spectral-domain optical coherence tomography (OCT) to show the characteristics of choroidal abnormalities. METHODS: Retrospective case series. Six eyes of three patients were examined by conventional fundus examinations, near-infrared monochromatic light reflectance (NIR-R) and NIR-AF, OCT, fluorescein angiography, and indocyanine green angiography. RESULTS: All eyes showed multiple bright patchy regions in the choroid of the posterior pole with NIR-R. NIR-AF revealed high fluorescent regions of similar sizes at fundus locations identical to those shown by NIR-R. In one case, hypofluorescent regions were shown by indocyanine green angiography in the bright fluorescent region shown by NIR-AF. The other two cases showed no abnormality under conventional fundus examination or fluorescein angiography. OCT images crossing the bright patchy region showed irregular hyper-reflectivity in the choroid in two cases and hyporeflectivity in one case. CONCLUSIONS: NIR-AF demonstrated that dense melanin was included in the choroidal nodules of neurofibromatosis type 1. The choroidal nodules showed hyper- or hyporeflectivity in the choroid on OCT, which did not affect the retinal structure.

Treatment of macular edema due to branch retinal vein occlusion with single or multiple intravitreal injections of bevacizumab.

PURPOSE: We examined the predictive factors for final visual acuity (VA) with macular edema of branch retinal vein occlusion (BRVO) treated by intravitreal injection of bevacizumab (IVB) and examined the differences between patients without recurrent macular edema due to BRVO after a single IVB and patients treated with multiple IVB because of recurrent macular edema. METHODS: In this retrospective study, 37 eyes of 37 patients with BRVO were treated with IVB and followed up for more than 24 weeks. Eighteen eyes showed no recurrence of macular edema after a single IVB (single IVB group). The remaining 19 eyes showed recurrent macular edema and underwent multiple IVB (multiple IVB group). VA and morphologic parameters of optical coherence tomography were examined. RESULTS: Mean VA, central retinal thickness, and mean retinal thickness in a circular region of 1-mm diameter at the fovea improved significantly with IVB treatment in both groups. Final VA was correlated with baseline VA and integrity grade of the photoreceptor inner and outer segment (IS/OS) line beneath the fovea. CONCLUSION: Baseline VA and IS/OS line grade at 4 weeks may be predictive factors for final VA.

One-year results of photodynamic therapy combined with intravitreal ranibizumab for exudative age-related macular degeneration.

Purpose. To evaluate the effects of photodynamic therapy (PDT) combined with intravitreal injection of ranibizumab (IVR) for exudative age-related macular degeneration (AMD). Methods. Retrospective case series. Thirty eight eyes of 38 patients with exudative AMD underwent combined therapy consisting first of IVR, followed by PDT within a week and the second IVR at 1 month. All patients were followed up for more than 12 months. The best corrected visual acuity (BCVA) and central macular thickness (CMT) were examined. Results. The mean number of IVR and PDT sessions were 2.9 ± 1.3 and 1.1 ± 0.3, respectively. The mean BCVA and CMT were significantly improved to 0.38 logMAR units (P < 0.01) and 240 µm (P < 0.01) at 12 months, respectively. Thirty-six of 38 eyes (94.8%) improved or maintained BCVA at 12 months. Conclusion. PDT combined with IVR for exudative AMD was effective at improving visual acuity and CMT with a low recurrence rate for 12 months.

Intravitreal injection of bevacizumab combined with macular grid laser photocoagulation for macular edema in branch retinal vein occlusion.

PURPOSE: To evaluate the effects of combined therapy of intravitreal injections of bevacizumab (IVB) and additional macular grid laser photocoagulation for recurrent macular edema in branch retinal vein occlusion (BRVO). METHODS: This was a retrospective interventional case series in which 44 eyes of 44 patients with macular edema due to BRVO were studied. The mean follow-up term was 77.2 ± 12.4 weeks. All patients underwent IVB as a primary therapy. After two to three IVB, 19 of the 44 eyes (43.2%) underwent laser photocoagulation in the macular edema area to prevent the recurrence of the edema. In the other 25 eyes (56.8%), macular edema was successfully treated with IVB only. Visual acuity and central macular thickness (CMT) were examined during the follow-up. RESULTS: The mean visual acuity and the mean CMT in both groups improved significantly after the IVB. Following macular grid laser photocoagulation for recurrent macular edema, the mean visual acuity was maintained for 24 weeks, however, the mean CMT increased significantly after 12 weeks. CONCLUSIONS: Additional grid laser photocoagulation for recurrent macular edema in BRVO after IVB maintained mean visual acuity with limited effects on the further recurrence of macular edema.

Short-term results of canaloplasty surgery for primary open-angle glaucoma in Japanese patients.

PURPOSE: To report surgical results of canaloplasty surgery for primary open-angle glaucoma (POAG) in Japanese patients. METHODS: Eleven eyes of 9 POAG patients underwent canalopasty surgery at Toyama University Hospital. Three eyes of 3 patients underwent canaloplasty alone and 8 eyes of 6 patients underwent canaloplasty combined with cataract surgery. Canaloplasty was performed with a 10-0 polypropylene tensioning suture and an iTrack™ 250A microcatheter. All patients were followed up for 12 months. Changes in intraocular pressure (IOP) and postoperative complications were examined. RESULTS: Mean preoperative IOP was 23.4 ± 5.5 mm Hg. Mean number of antiglaucoma drops was 2.8 ± 0.6 before canaloplasty and decreased to 1.2 ± 0.8 at 12 months after canaloplasty (p < 0.01). Mean IOP decreased postoperatively, being 13.7 ± 2.8 mm Hg at 1 month, 12.8 ± 3.5 mm Hg at 3 months, 14.0 ± 4.4 mm Hg at 6 months, and 15.0 ± 4.1 mm Hg at 12 months. The most frequent postoperative complication was mild hyphema (45.5%), which disappeared within 14 days after surgery. CONCLUSIONS: Canaloplasty may be an alternative surgery for POAG patients to reduce IOP to a value of approximately 15 mm Hg.

[Short-term effects of intravitreal injection of bevacizumab on macular edema due to central retinal vein occlusion].

PURPOSE: To examine the short-term effects of intravitreal injections of bevacizumab on macular edema due to central retinal vein occlusion (CRVO). METHODS: Twenty one eyes of 21 consecutive patients with macular edema due to CRVO were included. The patients received intravitreal injections of 1.25 mg bevacizumab at the initial examination. They were followed up with best-corrected visual acuity (BVCA), fluorescein angiography, and central macular thickness (CMT) by optical coherence tomography for more than 4 months. Whenever the macular edema recurred, another intravitreal bevacizumab was given. RESULTS: The mean age of the patients was 68.1 +/- 11.8 and the mean follow up was 6.5 +/- 2.6 months. The mean baseline BVCA (logMAR) and CMT were 0.79 +/- 0.45 and 699 +/- 194 microm, respectively. After treatment, the mean BVCA improved significantly at 1 week (0.52 +/- 0.46, p<0.001), 1 month (0.48 +/- 0.46, p<0.001), 2 months(0.56 +/- 0.43, p<0.02), and 4 months (0.51 +/- 0.47, p<0.001). The mean CMT also decreased significantly at 1 week (296 +/- 86 microm, p<0.001), 1 month (286 +/-132 microm, p<0.001), 2 months (464 +/- 249 microm, p<0.05) and 4 months (362 +/- 198 microm, p<0.001). Similar effects on reducing CMT were obtained both after the initial injection and the second injection of bevacizumab. CONCLUSION: Intravitreal injection of bevacizumab improved visual acuity and macular edema due to CRVO.