Young-on Jo

Interleukin‐18 regulates pathological intraocular neovascularization

Recently, the proinflammatory cytokine IL‐18 has been shown to have a role in angiogenesis. This study aimed to elucidate its role in abnormal neovascularization (NV) in an oxygen‐induced retinopathy (OIR) mouse model of the retinopathy seen in human premature newborns. IL‐18 was constitutively expressed in the retina in C57BL/6 mice, but expression transiently dropped on Day 17 after birth in mice exposed to 75% oxygen for 5 days between Days 7 and 12. Coincident with the IL‐18 reduction in oxygen‐treated mice, vascular endothelial growth factor was expressed in the retina, and OIR developed. By Day 24, NV in the retina had regressed to normal levels. By contrast, IL‐18 knockout mice, exposed to elevated oxygen concentrations, developed more severe OIR on Day 17, and it is important that this persisted until Day 24. This suggested that IL‐18 negatively regulated retinal NV. To investigate this further, we administrated recombinant IL‐18 to C57BL/6 mice during the development of OIR but found no significant inhibition of retinopathy. However, when IL‐18‐binding protein was administered during the OIR recovery phase to neutralize endogenous IL‐18, OIR was still apparent on Day 24. We therefore concluded that IL‐18 regulates pathogenic retinal NV by promoting its regression rather than inhibiting its development. This suggests some useful, new approaches to treating retinopathy in humans.

Establishment of a new animal model of focal subretinal fibrosis that resembles disciform lesion in advanced age-related macular degeneration.

PURPOSE Subretinal fibrosis causes damage to visual acuity, especially if the lesion is in the macula, as is frequently observed in advanced age-related macular degeneration. Exudate leukocytes form abnormal vessels that initiate regional inflammation accompanied with local glial proliferation and matrix production. The purpose of this study was to establish an animal model of focal subretinal fibrosis. METHODS Macrophage-rich peritoneal exudate cells (PECs) were injected into the subretinal space of C57BL/6 or MCP-1 knockout (KO) mice. Seven days later, the size of the subretinal fibrotic tissue was evaluated by the adherent area of glial fibrillary acidic protein (GFAP)-positive retinal glial cells on choroidal flat mounts. Myofibroblastic changes and collagen synthesis were detected by α-smooth muscle actin (α-SMA) and Masson trichrome staining of the histologic section, respectively. α-SMA expression was also examined on retinal pigment epithelium (RPE) cells during co-culture with activated macrophages. RESULTS Subretinal fibrous tissue was observed by funduscopy in PEC-injected mice after 7 days. The tissue consisted of a monotonous, low-cell-density area that expressed α-SMA with collagen synthesis. Both steroid and antioxidant treatment can reduce residual glia. Because PEC-injected MCP-1 KO mice showed less residual glia, not only exogenous macrophages, but also intrinsic macrophages were activated. The macrophages directly induced myofibrotic changes in RPE cells in vitro. CONCLUSIONS Activated macrophages form subretinal fibrosis when they are placed in the subretinal space and induce myofibrotic changes in RPE cells.

Diurnal Variation of Retina Thickness Measured with Time Domain and Spectral Domain Optical Coherence Tomography in Healthy Subjects

PURPOSE. To investigate diurnal variations in macular thickness and total macular volume using time domain optical coherence tomography (TD-OCT) and spectral domain OCT (SD-OCT) in healthy subjects. METHODS. Data were derived from 52 eyes of 52 healthy subjects. Macular thickness, macular volume was measured by using TD-OCT and SD-OCT at 8 AM and 6 PM. RESULTS. Comparing TD-OCT measurements, retinal thickness was significantly greater in the afternoon than in the morning in 3 of 9 grid subfields: central macular thickness (CMT) (194 vs. 190 μm; P = 0.006), superior inner area (276 vs. 273 μm; P = 0.010), and temporal inner area (261 vs. 258 μm; P = 0.006). In SD-OCT measurements, CMT, pericentral macular thickness, and macular volume did not differ significantly between the morning and the afternoon. Comparing the absolute variation in the parameters measured by the two devices, central macular thickness and temporal inner area thickness differed significantly (P = 0.015, P = 0.029), whereas other area thicknesses and macular volumes did not. Comparing the relative variation of the two devices, CMT and temporal inner area thickness differed significantly (P = 0.014, P = 0.027), whereas other area thicknesses and macular volume showed no significant difference. The moduli of variations for CMT, macular volume, and pericentral macular thickness were significantly lower using SD-OCT than using TD-OCT. CONCLUSIONS. The diurnal variation of the TD-OCT measurements was likely due to the limited repeatability of the device rather than to tissue variation. Diurnal variation was not found using SD-OCT, which has better repeatability.

Prediction of Retinal Ischemia in Branch Retinal Vein Occlusion: Spectral-Domain Optical Coherence Tomography Study.

PURPOSE To investigate the relationship between spectral-domain optical coherence tomography (SD-OCT) measurements and retinal nonperfusion in patients with branch retinal vein occlusion (BRVO). METHODS Forty-one patients with BRVO who had recovered from macular edema and had been followed for ≥2 years were included via retrospective, medical record review. Patients were divided into two groups that included 20 nonischemic eyes and 21 ischemic eyes, and 41 fellow control eyes were also included. Using SD-OCT, we measured the thickness of the macular layer, ganglion cell-inner plexiform layer (GC-IPL), and retinal nerve fiber layer (RNFL) in both the BRVO-affected and fellow eyes. The eyes were subdivided into affected and nonaffected areas of BRVO. Each area of normal fellow eyes and BRVO eyes was compared between the two groups. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic ability of the OCT measurements for ischemic BRVO. RESULTS The macula, the GC-IPL, and RNFL in the BRVO-affected area were significantly thinner compared to those of the fellow eyes in the two groups. The thickness of macula, GC-IPL, and RNFL in the ischemic BRVO group was also significantly less than in the nonischemic BRVO group. In the ROC curve analysis of a total of 82 eyes, the area under the ROC curve of the RNFL on the ischemic BRVO was the highest at 0.906, followed by the GC-IPL (0.824) and the macula (0.768). CONCLUSIONS The thickness of macula, GC-IPL, and RNFL in the ischemic BRVO group was significantly reduced compared to the nonischemic BRVO group, especially in the RNFL.

Ganglion Cell-Inner Plexiform Layer Thickness in Retinal Diseases: Repeatability Study of Spectral-Domain Optical Coherence Tomography.

PURPOSE To analyze the repeatability of measuring the thickness of the ganglion cell-inner plexiform layer using spectral-domain optical coherence tomography by auto-segmentation in various retinal diseases. DESIGN Test-retest reliability analysis. METHODS A total of 180 patients who visited our clinic between April and December 2013 were included. An experienced examiner obtained 2 consecutive measurements from a macular cube 512 × 128 scan. The patients were divided into 3 groups according to central macular thickness. Repeatability was determined by comparing the average, minimum, and 6 sectoral ganglion cell-inner plexiform layer thickness values among groups. RESULTS Data from 165 of the 180 patients were included in the analysis. Measurement errors occurred in 3 patients (6%) in the macular atrophy group and 12 (20%) in the edema group. The measurement repeatability for ganglion cell-inner plexiform layer thickness was high in the normal eye group (average intraclass correlation coefficient [ICC], 0.994; coefficient of variation [COV], 0.7%; and test-retest variability, 1.1 μm), relatively low in the macular edema group (average ICC, 0.845; COV, 18.7%; and test-retest variability, 27.8 μm), and lowest in the macular atrophy group (ICC, 0.610; COV, 30.4%; and test-retest variability, 29.2 μm) compared to the normal eye group. CONCLUSIONS The repeatability of ganglion cell-inner plexiform layer thickness measurements was lower in the macular edema and atrophy groups. The impact of changes in macular shape caused by various retinal diseases should be taken into consideration when measuring ganglion cell-inner plexiform layer thickness in other diseases such as glaucoma and neuro-ophthalmology.

Sectoral Retinal Nerve Fiber Layer Thinning In Branch Retinal Vein Occlusion

Purpose: To analyze longitudinal changes in the retinal nerve fiber layer (RNFL) thickness in branch retinal vein occlusion (BRVO) using optical coherence tomography. Methods: The authors prospectively analyzed 20 eyes in 20 patients diagnosed with branch retinal vein occlusion (BRVO) and followed for more than 1 year. The RNFL thickness of the normal and occluded eyes was measured at the time of diagnosis and at 1, 3, 6, and 12 months. The authors compared the changes in the occluded eye over the follow-up and the differences between two eyes at each time. They also analyzed the area opposite the occluded area. Results: The thickness of the RNFL in BRVO was significantly reduced at 1, 3, 6, and 12 months (P = 0.005 at 1 month and P = 0.001 at 3, 6, and 12 months) compared with initial thickness. The RNFL thickness at 3 months did not differ significantly between 2 eyes, whereas at 6 months and 12 months, significant (P = 0.032, P = 0.002, respectively.) thinning was observed in the occluded eye. Analysis of the area opposite that of BRVO revealed no significant (P > 0.05) change during the follow-up and no difference between the 2 eyes. Conclusion: There was a significant decrease in RNFL thickness over time in BRVO and significant thinning at 6 months compared with the normal eye. Retinal nerve fiber layer thinning needs to be differentiated from glaucoma or systemic disease, but it should be considered the natural course after BRVO.

Hydrophobic versus double-square-edged hydrophilic foldable acrylic intraocular lens: effect on posterior capsule opacification.

PURPOSE: To evaluate posterior capsule opacification (PCO) 2 years after cataract surgery with implantation of a hydrophobic acrylic or single‐piece sharp‐edged hydrophilic acrylic intraocular lens (IOL). SETTING: Toyama Prefectural Central Hospital, Toyama, Japan. DESIGN: Case‐control study. METHODS: Patients with bilateral senile cataract were prospectively randomized to receive a hydrophobic IOL (Acrysof SA60AT) in 1 eye and a hydrophilic IOL (Meridian HP60M) in the other eye. The PCO density value, degree of IOL decentration and tilt, and anterior chamber depth (ACD) were measured using Scheimpflug videophotography 1, 6, 12, 18, and 24 months after surgery. Visual acuity and the number of eyes requiring neodymium:YAG laser capsulotomy were also assessed. RESULTS: The study evaluated 16 eyes (63 patients). The PCO value in the hydrophilic group increased significantly with time and was statistically significantly greater than in the hydrophobic group 18 and 24 months postoperatively (both P<.001). The capsulotomy rate was statistically significantly higher in the hydrophilic group than in the hydrophobic group (P<.01). Visual acuity in the hydrophilic group worsened significantly with time and was statistically significantly worse than in the hydrophobic group at 18 and 24 months (both P<.001). Intraocular lens decentration, IOL tilt, and the ACD did not change significantly during the follow‐up in either group (P>.05), and there were no statistically significant postoperative differences in these parameters between the 2 IOL groups (P>.05). CONCLUSION: Two years after surgery, the hydrophobic IOL group had less PCO, a lower capsulotomy rate, and better visual acuity than the hydrophilic IOL group. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned.

Thickness of the Macula, Retinal Nerve Fiber Layer, and Ganglion Cell Layer in the Epiretinal Membrane: The Repeatability Study of Optical Coherence Tomography.

PURPOSE To analyze the repeatability of measurements of the thicknesses of the macula, retinal nerve fiber layer (RNFL), and ganglion cell inner plexiform layer (GCIPL) using spectral-domain optical coherence tomography (SD-OCT) in the epiretinal membrane (ERM). METHODS The prospective study analyzed patients who visited our retinal clinic from June 2013 to January 2014. An experienced examiner measured the thicknesses twice using macular cube 512 × 128 and optic disc cube 200 × 200 scans. The repeatability of the thicknesses of the macula, RNFL, and GCIPL were compared using the intraclass correlation coefficient (ICC) of two groups based on the central macular thickness (group A, ≤ 450 μm; group B, > 450 μm). RESULTS A total of 88 patients were analyzed. The average thicknesses of the central macula, RNFL, and GCIPL were 256.5, 96.6, and 84.4 μm, respectively, in the normal fellow eye and 412.3, 94.6, and 56.7 μm in the affected eye. The ICCs of the central macula, RNFL, and GCIPL were 0.995, 0.994, and 0.996, respectively, for the normal fellow eye and 0.991, 0.973, and 0.881 for the affected eye. The average thicknesses of the central macula, RNFL, and GCIPL in group A were 360.9, 93.5, and 63.4 μm, respectively, and the ICCs were 0.997, 0.987, and 0.995. The thicknesses in group B were 489.5, 96.2, and 46.6 μm, respectively, and the ICCs were 0.910, 0.942, and 0.603, significantly lower repeatability compared with group A (P < 0.05). CONCLUSIONS The macular contour change with the ERM results in low repeatability and tendency to be measured thinner in GCIPL thickness using SD-OCT. This can be explained by the unstable gaze of the patient due to decreased visual acuity and autosegmentation error following changes in the macula.

Longitudinal Changes in Retinal Nerve Fiber Layer Thickness after Vitrectomy for Rhegmatogenous Retinal Detachment

PURPOSE To investigate the longitudinal changes in retinal nerve fiber layer (RNFL) thickness after pars plana vitrectomy for rhegmatogenous retinal detachment. METHODS This prospective study examined 33 vitrectomy patients who were diagnosed with rhegmatogenous retinal detachment. Optical coherence tomography was conducted 6, 12, and 24 months after vitrectomy to investigate the changes in RNFL thickness. The RNFL thickness in the retinal detached area of the affected eye was compared with its mirror image in the fellow eye. RESULTS The respective RNFL thickness in retinal-detached area and its mirror image in the fellow eye was 120.7 ± 13.5 μm and 124.7 ± 21.5 μm at 6 months following vitrectomy (P > 0.05); 114.1 ± 19.6 μm and 124.0 ± 16.6 μm at 12 months (P < 0.05); and 107.5 ± 17.2 μm and 123.8 ± 14.3 μm at 24 months (P < 0.05). A significant difference was detected between the RNFL thickness in the detached area and the fellow eye after 12 and 24 months. The difference in the RNFL thickness in the area of undetached retina in the affected eye and its mirror image in the fellow eye during follow-up did not differ significantly (P > 0.05). CONCLUSIONS In patients undergoing vitrectomy for rhegmatogenous retinal detachment, the RNFL was significantly thinner in the area of the detached retina than in the fellow eye 12 and 24 months postoperatively.

Bilateral central serous chorioretinopathy with retinal pigment epithelium tears following epidural steroid injection

The cause of central serous chorioretinopathy (CSC) is mostly idiopathic. Other cause such as stressful event or use of corticosteroid has been associated with severe form of CSC. Atypical presentation of CSC has widespread degeneration of retinal pigment epithelium (RPE) or bullous retinal detachment. In this report, we describe a case of bilateral CSC with RPE tear after epidural steroid injection.