Purpose.: To analyze the intraocular pharmacokinetic properties of intravitreally injected ranibizumab in vitrectomized and nonvitrectomized rabbit eyes. Methods.: A procedure consisting of 25-gauge pars plana vitrectomy without lensectomy and posterior vitreous detachment was performed in 18 rabbit eyes, and 18 nonvitrectomized rabbit eyes served as controls. Ranibizumab (0.25 mg/0.025 mL) was intravitreally injected in all the vitrectomized and nonvitrectomized eyes. The eyes were enucleated at 1 hour or 1, 2, 5, 14, or 30 days after the intravitreal injections and frozen at −80°C. Ranibizumab concentrations in the vitreous, aqueous humor, and retina were determined using indirect enzyme-linked immunosorbent assay. Results.: Vitreous clearance of ranibizumab showed a 2-phase elimination. The vitrectomized and nonvitrectomized eyes showed comparable rates of vitreous clearance of ranibizumab. The vitreous half-life of ranibizumab for up to 14 days was 2.51 and 2.75 days in vitrectomized and nonvitrectomized eyes, respectively. Throughout the 30-day period after intravitreal injection, there were no statistically significant differences between the concentrations of ranibizumab in the vitreous, aqueous humor, and retina of vitrectomized eyes and those in nonvitrectomized eyes. Concentrations of ranibizumab in the vitreous peaked 1 hour after injection, with a mean concentration of 118.01 and 91.61 μg/mL in vitrectomized and nonvitrectomized eyes, respectively. The elimination rate constant of intravitreal ranibizumab in 1-phase analyses showed only a 9% increase in vitrectomized eyes compared to nonvitrectomized eyes. Conclusions.: Overall intraocular pharmacokinetic properties of ranibizumab in vitrectomized eyes were similar to those in nonvitrectomized eyes. Our data do not support the use of different dosing regimens of ranibizumab in vitrectomized eyes.

We aimed to investigate the prevalence of diabetic retinopathy (DR) in patients with diabetic foot ulcer (DFU) and elucidate the association between DR and DFU severities and their shared risk factors. A retrospective review was conducted on DFU patients who underwent ophthalmic and vascular examinations within 6 months; 100 type 2 diabetic patients with DFU were included. The medical records of 2496 type 2 diabetic patients without DFU served as control data. DR prevalence and severity were assessed in DFU patients. DFU patients were compared with the control group regarding each clinical variable. Additionally, DFU patients were divided into two groups according to DR severity and compared. Out of 100 DFU patients, 90 patients (90%) had DR and 55 (55%) had proliferative DR (PDR). There was no significant association between DR and DFU severities (R = 0.034, p = 0.734). A multivariable analysis comparing type 2 diabetic patients with and without DFUs showed that the presence of DR [OR, 226.12; 95% confidence interval (CI), 58.07–880.49; p < 0.001] and proliferative DR [OR, 306.27; 95% CI, 64.35–1457.80; p < 0.001), higher HbA1c (%, OR, 1.97, 95% CI, 1.46–2.67; p < 0.001), higher serum creatinine (mg/dL, OR, 1.62, 95% CI, 1.06–2.50; p = 0.027), older age (years, OR, 1.12; 95% CI, 1.06–1.17; p < 0.001), higher pulse pressure (mmHg, OR, 1.03; 95% CI, 1.00–1.06; p = 0.025), lower cholesterol (mg/dL, OR, 0.94; 95% CI, 0.92–0.97; p < 0.001), lower BMI (kg/m², OR, 0.87, 95% CI, 0.75–1.00; p = 0.044) and lower hematocrit (%, OR, 0.80, 95% CI, 0.74–0.87; p < 0.001) were associated with DFUs. In a subgroup analysis of DFU patients, the PDR group had a longer duration of diabetes mellitus, higher serum BUN, and higher serum creatinine than the non-PDR group. In the multivariable analysis, only higher serum creatinine was associated with PDR in DFU patients (OR, 1.37; 95% CI, 1.05–1.78; p = 0.021). Diabetic retinopathy is prevalent in patients with DFU and about half of DFU patients had PDR. No significant association was found in terms of the severity of these two diabetic complications. To prevent blindness, patients with DFU, and especially those with high serum creatinine, should undergo retinal examinations for timely PDR diagnosis and management.

Purpose: To compare the pharmacokinetics (PKs) of intravitreally injected bevacizumab in vitrectomized versus nonvitrectomized control rabbit eyes. Methods: Twenty-five-gauge pars plana vitrectomy without lensectomy was performed in 17 right rabbit eyes (V) and 18 nonvitrectomized right rabbit eyes served as controls (C). After 1.25 mg/0.05 mL intravitreal bevacizumab (IVB) injections, eyes were enucleated at 1 h, 1, 2, 5, 14, and 30 days after the injection and immediately frozen at −80°C. Bevacizumab concentrations were determined after separation of frozen vitreous and aqueous humor (AH) compartments using indirect enzyme-linked immunosorbent assay. Bevacizumab concentration–time data were analyzed to obtain PK data. Results: Vitreous clearance of IVB consisted of 2 phases, the first fast distribution and second slow elimination phase. Clearance of IVB was accelerated in V eyes only during the first phase and not in the second phase. The vitreous concentration percent ratios between V and C eyes were 94.7% (1 h), 70.5% (1 day), 89.2% (2 days), 94.2% (5 days), 99.2% (14 days), and 79.1% (30 days). Overall vitreous half-lives were 6.99 and 7.06 days for V and C eyes, respectively (1.6-h difference). Conclusion: Overall IVB PKs in rabbit eyes after vitrectomy without lensectomy are not substantially different from nonvitrectomized control eyes.

Central serous chorioretinopathy (CSC) is a common condition characterized by serous detachment of the neurosensory retina at the posterior pole. We built a deep learning system model to diagnose CSC, and distinguish chronic from acute CSC using spectral domain optical coherence tomography (SD-OCT) images. Data from SD-OCT images of patients with CSC and a control group were analyzed with a convolutional neural network. Sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUROC) were used to evaluate the model. For CSC diagnosis, our model showed an accuracy, sensitivity, and specificity of 93.8%, 90.0%, and 99.1%, respectively; AUROC was 98.9% (95% CI, 0.983–0.995); and its diagnostic performance was comparable with VGG-16, Resnet-50, and the diagnoses of five different ophthalmologists. For distinguishing chronic from acute cases, the accuracy, sensitivity, and specificity were 97.6%, 100.0%, and 92.6%, respectively; AUROC was 99.4% (95% CI, 0.985–1.000); performance was better than VGG-16 and Resnet-50, and was as good as the ophthalmologists. Our model performed well when diagnosing CSC and yielded highly accurate results when distinguishing between acute and chronic cases. Thus, automated deep learning system algorithms could play a role independent of human experts in the diagnosis of CSC.

Purpose. To investigate both the effect of diabetic macular edema (DME) on measured peripapillary retinal nerve fiber layer (RNFL) thickness and the effect of intravitreal bevacizumab injection on RNFL thickness using spectral-domain optical coherence tomography (SD-OCT) in patients with diabetic retinopathy. Methods. We compared the SD-OCT RNFL thickness profiles between eyes with and without DME (DME [n = 42]; without DME [n = 53]) and conducted an interventional study for evaluating the effect of DME on RNFL thickness. Six sectorial and the global RNFL (gRNFL) thicknesses were compared between the two groups. To evaluate the intraindividual effect of DME on RNFL thickness, 1-month follow-up OCT data of 42 eyes that received an intravitreal bevacizumab injection were compared with preinjection data. Results. The six sectorial and gRNFL thicknesses were greater in the DME group than the non-DME group (P < 0.05). The gRNFL thickness significantly correlated with the central foveal thickness (CFT) (R = 0.470, P < 0.001) and total macular volume (R = 0.786, P < 0.001). The 42 eyes that received intravitreal bevacizumab injections showed significant decreases of the CFT (P < 0.001) and gRNFL thickness (P < 0.001) after injection. Additionally, the changes in macular thickness and RNFL thickness were significantly correlated (R = 0.576, P < 0.001). Conclusions. The RNFL thickness was generally increased in patients with DME, and the increment correlated with the degree of macular edema. While long-lasting DME resulted in RNFL thickening in all sectors, short-term DME resolution mainly influenced the temporal and nasal RNFL thicknesses. Cautious interpretation is recommended for evaluation of glaucoma using RNFL thickness in diabetic patients, especially patients with DME.