PURPOSE:To report our findings in three cases of a clouding of the anterior surface of an implanted intraocular lens that developed within 14 days after implantation.OBSERVATIONS:Three eyes were implanted with the same model IOL and a steam-like clouding developed on the anterior surface of the IOL. The clouding occurred on days 4, 7, and 14 after the implantation in an area of the IOL that was in contact with the aqueous humor. The clouding was accompanied by a reduction of vision in all cases but without any other abnormalities such as inflammation. The clouding was resolved by irrigation and aspiration of the anterior chamber in 2 cases at 2 and 34 days after the onset, and a spontaneous disappearance in 1 case at 14 days after the onset of the clouding. After the disappearance of the clouding, the visual acuity improved, and there were no recurrences. The solution used to irrigate the anterior chamber was collected and examined to confirm the absence of cellular materials. Elemental analyses confirmed that sodium and chloride were the predominant ions. The IOL implanted was the XACT lens (Advanced Vision Science, USA) which is a hydrophobic acrylic IOL and is characterized by having higher water content compared to other IOLs. In addition, it is packaged in 0.9% saline to maintain the pre-hydrated condition. These aspects may be related to the cause of the clouding. This IOL was implanted in 3271 eyes in our clinic, and 3 of them (0.09%) developed this clouding.CONCLUSIONS AND IMPORTANCE:We report our findings in 3 eyes that developed a clouding on the anterior surface of the lens soon after implantation. The clouding was localized to the area in contact with the aqueous. The cause of the clouding was not determined.

Silicone oil (SO) is an intraocular surgical adjuvant that reduces the surgical complications in refractory retinal diseases, although membrane and cellular proliferation is often seen even in SO-filled eyes. We hypothesised that the fluid in the space between the SO and the retina, named the “sub-silicone oil fluid (SOF)”, enhances these biological responses. We proposed a safe method for SOF extraction. We also analysed inflammatory cytokine expressions and SOF osmotic pressures from eyes with rhegmatogenous retinal detachment (RRD), proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR) and macular hole-associated retinal detachment (MHRD). Interleukin (IL)-10, IL-12p40, IL-6, monocyte chemotactic protein-1, and vascular endothelial growth factor (VEGF) in the SOF with PVR were significantly higher than in those with RRD or MHRD. Fibroblast growth factor-2, IL-10, IL-12p40, IL-8, VEGF, and transforming growth factor beta 1 levels in eyes with exacerbated PDR indicated a significantly higher expression than those with simple PDR. IL-6 and tumour necrosis factor alpha in eyes with exacerbated PVR demonstrated a significantly higher expression than in those with simple PVR. However, there was no difference in SOF osmotic pressure between group of each disease. These studies indicate that disease-specific SOF is a significant reflection of disease status.

Ocular trauma is one of the leading causes of visual impairment worldwide. Because of the popularity of cataract surgeries, aged individuals with ocular trauma commonly have a surgical wound in their eyes. The purpose of this study was to evaluate the visual outcome of cases that were coincident with intraocular lens (IOL) ejection in the eyes with ruptured open-globe ocular injuries. Consecutive patients with open-globe ocular injuries were first reviewed. Patients' characteristics, corrected distance visual acuities (CDVAs) over 3 years after the trauma, causes of injuries, traumatic wound patterns, and coexistence of retinal detachment were examined. The relationships between poor CDVA and the other factors, including the complications of crystalline lens and IOL ejection, were examined. A total of 105 eyes/patients [43 eyes with rupture, 33 with penetrating, 28 with intraocular foreign body (IOFB), and 1 with perforating injuries] were included. Rupture injuries were common in aged patients and were mostly caused by falls, whereas penetrating and IOFB injuries were common in young male patients. CDVAs of the eyes with rupture injuries were significantly worse than those of the eyes with penetrating or IOFB injuries. CDVA from more than 50% of the ruptured eyes resulted in no light perception or light perception to 20/500. CDVA of the ruptured eyes complicated by crystalline lens ejection was significantly worse than that of those complicated by IOL ejection. The wounds of the ruptured eyes complicated by IOL ejection were mainly located at the superior corneoscleral limbus, whereas those of the eyes complicated by crystalline lens ejection were located at the posterior sclera. There were significant correlations between poor CDVA and retinal detachment and crystalline lens ejection. These results proposed a new trend in the ocular injuries that commonly occur in aged patients; history of cataract surgery might affect the final visual outcome after open-globe ocular injuries.

Purpose Proliferative vitreoretinopathy (PVR) is one of the most severe ocular diseases. Fibrotic changes in retinal cells are considered to be involved in the pathogenesis of PVR. Epithelial-mesenchymal transition (EMT) of RPE cells is one of the main concepts in the pathogenesis of fibrovascular membranes (FVMs) in PVR. In this study, we examined the expression of Caveolin-1 in human FVMs from patients with PVR. We also examined the role of Caveolin-1 in the pathogenesis of PVR. Methods Western blotting, real-time PCR, and immunohistochemistry were performed with human FVMs and mouse eyes with PVR. Cell migration assays were performed to evaluate the involvement of Caveolin-1 in EMT using primary human and mouse RPE cells. Results Caveolin-1 was expressed in human FVMs and upregulated in the mouse eyes with PVR. The alpha-smooth muscle actin (αSMA) expression and migration ability were increased in RPE cells with knockout or knockdown of Caveolin-1, whereas zonula occludens-1 (ZO-1) immunohistochemistry showed reduced morphology and expression of ZO-1. In addition, migration assays showed that Caveolin-1 reduction increased RPE cell migration abilities. Conclusions These results indicated that Caveolin-1 in RPE cells prevents PVR by blocking EMT.

PURPOSE:The purpose of this study was to determine microRNA expression in vitreous and subretinal fluid (SRF) samples from patients with retinal detachment (RD). The pathological importance of the identified microRNA transcript levels was analyzed in vitro.METHODS:Vitreous fluid was collected from 10 patients with macular hole (MH), vitreomacular traction syndrome (VMTS), or foveoschisis and from 11 patients with RD. Subretinal fluid was collected from 7 patients with RD. Of these, blood serum was collected in 4 patients. MicroRNA microarray profiling was performed to identify microRNA transcripts that were present in vitreous fluid, and more redundantly detected in SRF, of patients with RD, but not detected in control eyes. Western blotting and scratch assays were performed in ARPE-19 cells and primary human RPE cell lines transfected with microRNA to elucidate the effect of identified microRNA transcripts on epithelial-mesenchymal transition (EMT).RESULTS:MicroRNA microarray profiling revealed that hsa-miR-148a-3p was the most redundantly detected transcript in SRF and vitreous fluid from patients with RD, but not those with the other diseases. Expression levels of hsa-miR-148a-3p were higher in SRF samples than in blood serum samples in 3 out of 4 patients. Following hsa-miR-148a-3p mimic transfection, ARPE-19 and human RPE cells demonstrated increased expression of α-smooth muscle actin by Western blotting and increased migration ability during scratch assays.CONCLUSIONS:The results of the present study indicate that hsa-miR-148a-3p was specifically detected in RD and promotes EMT in RPE.

PURPOSETo evaluate the performance of a newly developed 23-G optical coherence tomography (OCT) probe in animal and human eyes.METHODSThe probe is a side-imaging OCT device with a scanning beam set 43° to the optical axis and a working distance of 1.5 to 2.0 mm. The performance of the OCT probe was tested during vitrectomy in porcine cadaver eyes and rabbit eyes in situ. Optical coherence tomography images of a normal retina, retinal break, optic disc, pars plicata of the ciliary body, and intraoperative surgical manipulations were recorded. The probe was also tested in a pilot study of clinical cases; intraoperative real-time OCT imaging was performed in three patients, including a 56-year-old woman with an epiretinal membrane.RESULTSThe OCT probe was able to delineate intraocular tissues, including the posterior retina, and even the most peripheral pars plicata in animal eyes. The OCT probe also successfully delineated intraoperative surgical maneuvers such as membrane peeling and the minute structures of the vortex veins, ora serrata, and vitreous incarceration in the scleral incision from the trocar with sufficient resolution in the patients. There were no complications resulting from its use.CONCLUSIONSThe ability of this new 23-G OCT probe to obtain images of intraoperative manipulations from the most peripheral tissues in animal and patient eyes suggests that it could enable surgeons to make better decisions during the course of intraocular surgery.

Purpose: We report a newly developed device to fragment thrombi in retinal vein occlusion.Methods: The new instrument consists of a 23-gauge (G) pipe and a 37-G needle with an internal wire. A total of 40 porcine eyes were used; 20 eyes for experiments in the branch retinal vein (BRV group) and 20 eyes for experiments in the central retinal vein (CRV group). We placed 25-G 3-port trocars, and core vitrectomy was performed. Another 23-G scleral incision was performed for insertion of the needle. The needle pierced the retinal vein at a distance of three-to four-or one-disc diameters from the optic disc (BRV or CRV group, respectively), and the internal wire was advanced toward the disc. The success rates of needle piercing and cannulation of the internal wire were recorded in each group. In the CRV group, the cannulation was deemed successful when the tip reached inside the optic disc. Real-time optical coherence tomography imaging also was performed using the Zeiss Rescan 700 device in porcine eyes. Histologic examination of the retinal vessel inserted with the internal wire was performed.Results: The success rates of needle piercing into the BRV and CRV were 85% and 95%, respectively. The success rates of cannulation of the internal wire into the BRV and CRV were 85% and 0%, respectively. The process of cannulation was recorded successfully with the Rescan 700. Histologic examination showed no damages to the endothelial cell layer.Conclusions: The needle and internal wire intended to be used for recanalization of BRV occlusion were successfully pierced and cannulated into the BRV.Translational Relevance: This newly developed device could become a treatment modality for retinal vein occlusion to fragment thrombi that present treatment methods cannot reach and remove directly.

F consecutive patients with fovea-off rhegmatogenous retinal detachment who had undergone 25guage vitrectomy and intraoperative optical coherence tomography with the RESCAN 700 (Carl Zeiss Meditec, Jena, Germany) were studied. The height of the subretinal fluid (SRF) at the fovea varied among the eyes before the intravitreal injection of perfluoro-n-octane (PFO). The PFO injection displaced the SRF, and the inner retinal layer of the macula, including the fovea, was immediately flattened (Figures 1, 2). Some of the SRF remained under the fovea and had a pyramidal shape with the base located against the retinal pigment epithelium in all 15 eyes (see Video, Fig. 1. Fundus photographs and spectral domain optical coherence tomographic images of a patient with a foveaoff rhegmatogenous retinal detachment. A. Fundus photograph taken with the Optomap camera showing a fovea-off rhegmatogenous retinal detachment. B. Spectralis spectral domain optical coherence tomographic image showing that the macula is detached. C. Surgical view with crosshairs of optical coherence tomography before the PFO injection (left). Horizontal and vertical B-scans show that SRF is present beneath the macular area (white arrowhead) including the fovea (middle, right). D. Surgical view with crosshairs in the optical coherence tomographic image after the PFO injection (left). Horizontal and vertical B-scans show that the SRF is displaced and the outer retinal corrugation is not present (white arrowhead). The retina is attached except for the fovea (middle, right). The SRF remains only at the fovea and has a pyramidal shape (yellow arrowhead). White arrows represent the force against the detached retina generated by the PFO. E. Surgical view and optical coherence tomographic images after air–fluid exchange (left). Horizontal and vertical Bscans show that some residual SRF remains only at the fovea and has a pyramidal shape (middle, right, yellow arrowhead). The outer retinal corrugation is not present (white arrowhead). F. Spectral domain optical coherence tomography Cirrus image showing that the SRF is not present and the pyramidal shape space is not present at 12 hours after the surgery (white arrowhead). G. Spectralis optical coherence tomographic image showing that the retina is attached and the pyramidal shape is not present 2 weeks after the surgery.

PURPOSE. To determine whether a correlation exists between the parameters of the focal macular ERGs (FMERGs) and the microstructural changes of the photoreceptors after successful surgery for fovea-off rhegmatogenous retinal detachment (RRD).METHODS. Twenty eyes of 20 patients who had undergone successful surgery to reattach the retina in eyes with fovea-off RRD were studied. Focal macular ERGs and spectral-domain OCT (SD-OCT) were recorded at 1 and 6 months after the surgery. Changes of the components of the FMERGs, as well as changes of the SD-OCT parameters including the length of the external limiting membrane (ELM), ellipsoid zone (EZ), cone interdigitation zone (CIZ), and size of the outer photoreceptor area (between ELM and RPE), were determined.RESULTS. During the postoperative period, the mean amplitudes of the a-waves increased by 1.4 times and the b-waves by 1.7 times. Spectral-domain OCT showed that the mean length of the EZ and CIZ and the size of the outer photoreceptor area had increased significantly at 6 months. The degree of the increase in the CIZ and outer photoreceptor area was significantly correlated with the increase in the amplitudes of the b-waves of the FMERGs (r = 0.56, P = 0.042, r = 0.57, P = 0.040, respectively; Spearman rank correlation test). However, the length of the EZ was not significantly correlated with the increase of the b-waves.CONCLUSIONS. A restoration of the EZ alone might not be enough to improve the FMERGs, and a restoration of the EZ accompanied by that of the CIZ was essential for the recovery of the FMERGs after fovea-off RRD.

To evaluate the color vision of patients with macular diseases after implanting a blue light-filtering intraocular lens (IOL) during vitrectomy. Twenty-seven patients had a blue light-filtering IOL implanted during vitrectomy for macular diseases (macular disease group), and 40 patients without macular disease had the same type of IOL implanted (non-macular disease group). The postoperative best-corrected visual acuity (BCVA) was ≥ 16/20 in all patients. The Farnsworth-Munsell 100-hue test was used to determine total error scores (TES) and mean error scores under photopic and mesopic conditions in both groups. The TES under mesopic conditions was significantly higher than that under photopic conditions in both groups (P < 0.05). However, the TES in the macular disease group was not significantly different from that of the non-macular disease group under both photopic and mesopic conditions. The mean error scores under photopic conditions for hues 11, 14, 16, 17, 18, and 20 (yellowish-red to yellow) were significantly higher in the macular disease group than in the non-macular disease group. The mean error scores for hues 7 and 85 (red) were significantly higher in the non-macular disease group than in the macular disease group. Under mesopic conditions, the mean error scores for hues 30, 60, and 61 were significantly higher in the non-macular disease group than in the macular disease group (P < 0.05). Our results indicate that blue light-filtering IOLs do not alter color discrimination in eyes with macular diseases, and these patients had good postoperative BCVA even under mesopic conditions.

Purpose To report the results of scleral buckling (SB) with or without photocoagulation (PC) and intravitreal bevacizumab (IVB) for stage 4 retinopathy of prematurity (ROP) eyes. Methods Forty-two eyes of 28 patients with SB and/or PC or IVB were studied. Twenty-nine eyes had stage 4A and 13 eyes had stage 4B ROP. Seventeen eyes underwent SB combined with additional intraoperative or postoperative treatments (combined group). Twenty-five eyes underwent SB without additional therapy (non-combined group). The concentrations of vascular endothelial growth factor (VEGF) in the aqueous humor determined by enzyme-linked immunosorbent assay were compared between the two groups. The initial and final reattachment rates were also compared. Results The gestational age and birth weight were 25.0 ± 2.0 weeks and 786 ± 222 g in the combined group, and 25.5 ± 2.1 weeks and 899 ± 315 g in the non-combined group. The postmenstrual age at the time of initial surgery was 38.0 ± 1.9 in the combined and 44.1 ± 4.0 weeks in the non-combined group ( P < 0.001). The initial reattachment rate was 92 % in stage 4A and 75 % in stage 4B of ROP eyes in the combined group, and the rate was 93 % in stage 4A and 33 % in stage 4B of ROP eyes in the non-combined group. The mean VEGF concentration in aqueous humor was 1923 ± 779 pg/ml in the combined group and 985 ± 303 pg/ml in the non-combined group ( P < 0.05). Conclusion Our results show that the retinal reattachment rate after combined therapy was comparable to that in the non-combined group. We conclude that combined therapy may be effective even in ROP eyes with high activity.

We conducted a study of the effect of intravitreal plasmin on retinal thickness in rabbits. Forty rabbit eyes were injected with 0.4, 1, 2, and 5 IU of plasmin (8 eyes/group). The same volume of BSS-plus(®) was injected in control eyes. Four eyes in each group underwent vitrectomy 60 minutes after the injections. The retinal thickness was measured in optical coherence tomographic (OCT) images before, 30 minutes, and 1 week after the injection. To study the effect of hyperosmolarity, 4 eyes received an injection of mannitol solution whose osmolarity was the same as the plasmin solutions. Thirty minutes after the plasmin injection, 4 eyes developed a serous retinal detachment (SRD). The mean retinal thickness including SRD was increased at 30 minutes in a dose-dependent way. The increase in eyes with 5 IU of plasmin was significantly greater than that in eyes with BSS-Plus(®) or 0.4 IU of plasmin (P = 0.0266, P = 0.0371, respectively). One week after the injection, SRD disappeared, and the mean retinal thickness decreased. The eyes injected with mannitol, the same osmolarity of 1, 2, 5 IU of plasmin, developed SRD at 30 minutes, and it disappeared after 1 week in all eyes. The results of this study demonstrated that an intravitreal injection of plasmin increases the retinal thickness in a dose-dependent way in rabbit eyes. The results with mannitol suggest that the increase in retinal thickness following plasmin is most likely caused by the hyperosmolarity of plasmin solution.

OBJECTIVE:The aim of this study was to identify the best sedation/analgesia protocol for laser photocoagulation (PC) of retinopathy of prematurity (ROP).STUDY DESIGN:This multicenter observational study included five hospitals, each using a specific sedation/analgesia protocol: local anesthesia with oxybuprocaine hydrochloride (Group L); intravenous pentazocine (Group P); intravenous fentanyl (Group F); air, oxygen and sevoflurane (AOS) inhalation (Group I). The groups were compared for pain responses, vital signs and adverse events.RESULTS:Heart rates and systemic blood pressures were elevated by PC in Groups L and P and Groups L, P and F, respectively. Moreover, poor analgesic efficacy was recognized in Groups L, P and F. In contrast, Group I experienced hypothermia, enteral feeding intolerance and apnea more frequently.CONCLUSION:From the viewpoint of sedation/pain relief, AOS anesthesia should be the best protocol. However, considering all the various factors together, the most reasonable one can be varied based on the patient's condition and hospital.

PURPOSETo determine how different intraoperative surgical procedures affect the midvitreous temperature.METHODSThe vitreous temperatures were monitored continuously with an intravitreal thermocouple in 87 eyes of 81 cases undergoing vitrectomy. Thirty-three eyes had diabetic retinopathy (DR), 35 eyes had an epiretinal membrane, and 19 eyes had an idiopathic macular hole. In eyes with DR, the correlation between the number of photocoagulations (PCs) and the change in temperature was analyzed. The temperature was also recorded before and after combined phacoemulsification and aspiration (PEA) and vitrectomy in 10 eyes.RESULTSThe average midvitreal temperature before the vitrectomy was 33.0 ± 1.3°C, 30.7 ± 1.7°C after core vitrectomy, 32.9 ± 1.3°C after membrane peeling, and 29.2 ± 1.4°C after peripheral vitrectomy. The temperature before PC was 29.8 ± 1.3°C, and it increased to 31.5 ± 1.9°C post-PC. The differences in the temperatures between consecutive procedures were significant (P < 0.01, respectively, Wilcoxon signed-rank test). The difference in the temperatures of the same procedures among the different diseases was not significant except after membrane peeling. A significant correlation was detected between the number of PCs and the duration of the PCs, and between the duration of PCs and the change in vitreous temperature after PC (r = 0.719, P = 0.0010, and r = 0.800, P = 0.0002, respectively, Spearman's rank correlation coefficient test). The temperature after PEA decreased significantly by 2.3°C.CONCLUSIONSOur results showed that vitreous temperatures vary during different vitrectomy procedures.