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To investigate the postoperative inflammatory and wound-healing responses after laser scleral microporation for presbyopia.
Thirty porcine eyes were used for the optimization of laser intensities first. Six monkeys (12 eyes) received scleral microporation with an erbium yttrium aluminum garnet (ErYAG) laser, and half of the eyes received concurrent subconjunctival collagen gel to modulate wound-healing response. The intraocular pressure (IOP) and the laser ablation depth were evaluated. The animals were euthanized at 1, 6, and 9 months postoperatively. The limbal areas and scleras were harvested for histologic analysis and immunofluorescence of markers for inflammation (CD11b and CD45), wound healing (CD90, tenascin-C, fibronectin, and HSP47), wound contraction (α-smooth muscle actin [α-SMA]), vascular response (CD31), nerve injury (GAP43), and limbal stem cells (P63 and telomerase).
In the nonhuman primate study, there was a significant reduction in IOP after the procedure. Overall, the ablation depth was 76.6% to 81.2% at 1 month and slightly decreased to 71.5% to 72.7% at 9 months. Coagulative necrosis around the micropores, as well as expression of CD11b, CD45, tenascin, fibronectin, HSP47, and GAP43, was distinct at 1 month but subsided with time. Collagen gel treatment significantly suppressed the upregulation of CD11b, CD45, fibronectin, and tenascin-C. The expression of CD90, α-SMA, and CD31 was minimal in all eyes.
The study demonstrated the course of inflammatory and wound-healing responses following laser scleral microporation. The tissue responses were small and self-limited, resolved with time, and were suppressed by concurrent collagen treatment. It provides a useful understanding of this new procedure.
The results would be helpful in the laser parameter modification to improve the long-term treatment stability.
The results would be helpful in the laser parameter modification to improve the long-term treatment stability.
To evaluate differences in parafoveal vascular density surrounding arterioles and venules in type 2 macular telangiectasia (MacTel).
Thirty-seven eyes (20 subjects) diagnosed with MacTel and 16 healthy eyes (10 subjects) were imaged with optical coherence tomography angiography between March 2016 and June 2019 in this single-center, observational, cross-sectional study. Arterioles and venules were manually identified, and perivascular density was generated using a custom MATLAB code. The primary outcome measure was the ratio of periarteriolar to perivenular vascular density (arteriovenous [A/V] capillary ratio) in the superficial and deep capillary plexuses across MacTel stages. The main secondary outcome measures were overall parafoveal vascular density (VD), periarteriolar VD, and perivenular VD.
In the superficial capillary plexus (SCP), the A/V capillary ratio was significantly higher in MacTel subjects than controls (0.914 vs. 0.892;
= 0.0044). learn more The greatest differences occurred between controls stage MacTel.
Proteinuria is the second most common complication after hypertension after systemic administration of bevacizumab. Therefore we aimed to analyze the effect of intravitreal bevacizumab (IVB) injection on proteinuria in patients with diabetes.
Patients scheduled to receive IVB injection from May 1, 2018, to December 31, 2018, were prospectively enrolled. In total, 53 patients with diabetes (26 with nonproliferative diabetic retinopathy and 27 with proliferative diabetic retinopathy) and 37 patients without diabetes were included. Urine tests were performed within 1 month of and 7 ± 1 days after IVB injection. Urinary protein, creatinine, and albumin concentrations were quantitatively measured, and urinary protein-to-creatinine ratio and urinary albumin-to-creatinine ratio (UACR) were calculated from these data before and after IVB injection.
The mean urinary microalbumin concentrations and urinary protein-to-creatinine ratio were significantly higher in patients with diabetes, both before and after IVB injection. There were no differences between patients with nonproliferative diabetic retinopathy and proliferative diabetic retinopathy. About 80% of patients with diabetes showed improved albuminuria or at least no harmful effect in terms of albuminuria. Patients with deteriorated baseline UACR showed more residual increase in UACR after IVB injection (
< 0.05 in all groups).
Close monitoring of renal function after IVB might be needed in patients with diabetes according to the severity of nephropathy.
Our results may provide information regarding the renal function of IVB-treated patients with diabetes.
Our results may provide information regarding the renal function of IVB-treated patients with diabetes.
To develop a model that can recapitulate key features of macular fibrosis in neovascular age-related macular degeneration (nAMD).
Adult C57BL/6J mice received three laser burns/eye to induce choroidal neovascularization (CNV). Seven days later, a second laser burn was directed to each of the neovascular lesions. Traditional laser-induced CNV was used as a control. Lesions were monitored at 10, 20, 30, and 40 days post-laser (p.l) treatment by fundus imaging, fundus fluorescein angiography, optical coherence tomography (OCT), and immunohistochemistry. The expression of collagen-1 (COL-1), fibronectin, α-smooth muscle actin, F4/80, complement factor B (CFB), Complement component 3 (C3), transforming growth factor-β (TGF-β), and fibroblast growth factor 2 (FGF2) in retina and retinal pigment epithelium/choroid was examined by immunofluorescence and reverse transcription polymerase chain reaction.
The two-stage laser protocol induced significantly larger lesions than the traditional laser-CNV by OCT and immunohistochemistry at all time points. Confocal microscopy detected COL-1
fibers and IBA1
/CD31
blood vessels in lesions from the two-stage laser protocol 30 to 40 days p.l. Lesions from traditional laser-CNV contain only COL-1
fibers but not blood vessels at this time point. Higher levels of proinflammatory (inducible nitric oxide synthase (iNOS), C3, CFB) and profibrotic (TGF-β, FGF2, and vascular endothelial growth factor) genes were detected in the retinas from the two-stage laser-induced lesions compared with the traditional laser-CNV lesion. Higher number of infiltrating F4/80 macrophages was also observed in and around the two-stage laser-induced fibrotic lesion.
The two-stage laser treatment induced subretinal fibrovascular membranes that persist over 40 days.
The model is a useful tool to study the mechanism of macular fibrosis in nAMD and test antifibrotic drugs.
The model is a useful tool to study the mechanism of macular fibrosis in nAMD and test antifibrotic drugs.
To investigate the potential of statistical and machine learning approaches to determine the diabetic status of patients from optical coherence tomography angiography (OCT-A) images.
This was a retrospective cross-sectional observational study based at Manchester Royal Eye Hospital, United Kingdom. OCT-A scans were sequentially selected from one eye of each of 182 patients who were either not diabetic, diabetic without retinopathy, or diabetic with retinopathy requiring hospital follow-up. Eligible images were analyzed by expert purpose-built automated algorithms to calculate clinically relevant outcome measures. These were used in turn as inputs to machine learning and statistical procedures to derive algorithms to perform clinically relevant classifications of patient images into the clinical groups. Receiver operating characteristic curves for the classifiers were evaluated and predictive accuracy assessed using area under curve (AUC).
For distinguishing diabetic patients from those without diabetes, the Random Forest classifier provided the highest AUC (0.8). For distinguishing diabetic patients with significant retinopathy from those with no retinopathy, the highest AUC was represented by logistic regression (0.91).
The study demonstrates the potential of novel techniques using automated analysis of OCT-A scans to diagnose patients with diabetes, or when diabetic status is known, to automatically determine those that require hospital input.
This work advances the concept of a rapid and noninvasive clinical screening tool using OCT-A to determine a patient's diabetic status.
This work advances the concept of a rapid and noninvasive clinical screening tool using OCT-A to determine a patient's diabetic status.
Continuous monitoring of elevated intraocular pressure and timely drug delivery for successful treatment of glaucoma are necessary to reduce intraocular pressure (IOP), which shows wide variations across the circadian pattern and in response to medication. This in vivo study presents a new contact lens-based method of optical IOP measurement or temperature-triggered drug elution.
A contact lens with moiré patterns of concentric circles measures the changes in eyeball diameter of a rabbit glaucoma model due to changes in IOP by superimposing a camera-captured image onto the micro pattern of the contact lens with a computer-assisted virtual reference image. Drug elution from the nanoporous bicontinuous microemulsion contact lens (BME-CL) into the eye of the rabbit was triggered by a temperature-responsive nanogel drug carrier.
The moiré pattern change on the contact lens was proportional to the IOP increase in the rabbit eye either ex vivo or in vivo and was also correlated with imaging-based alterations in the anterior chamber angle at a range of IOP values (3-40 mm Hg). The cumulative drug absorbed reached as high as 10.6 µg/mL aqueous humor until 7 days after wearing the BME-CL, and a 33% decrease in IOP was observed at 3 hours after drug elution.
The results suggest that continuous measurement and treatment of elevated IOP are feasible using moiré pattern-inscribed and thermosensitive drug-eluting contact lenses, respectively.
Pressure-sensing or thermosensitive contact lenses enable monitoring IOP or drug release triggered by body temperature for the treatment of glaucoma patients.
Pressure-sensing or thermosensitive contact lenses enable monitoring IOP or drug release triggered by body temperature for the treatment of glaucoma patients.
To compare performance of independently developed deep learning algorithms for detecting glaucoma from fundus photographs and to evaluate strategies for incorporating new data into models.
Two fundus photograph datasets from the Diagnostic Innovations in Glaucoma Study/African Descent and Glaucoma Evaluation Study and Matsue Red Cross Hospital were used to independently develop deep learning algorithms for detection of glaucoma at the University of California, San Diego, and the University of Tokyo. We compared three versions of the University of California, San Diego, and University of Tokyo models original (no retraining), sequential (retraining only on new data), and combined (training on combined data). Independent datasets were used to test the algorithms.
The original University of California, San Diego and University of Tokyo models performed similarly (area under the receiver operating characteristic curve = 0.96 and 0.97, respectively) for detection of glaucoma in the Matsue Red Cross Hospital dataset, but not the Diagnostic Innovations in Glaucoma Study/African Descent and Glaucoma Evaluation Study data (0.