Steam-like clouding observed on anterior surface of intraocular lens developed soon after implantation.

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.

Cytokine profiling in the sub-silicone oil fluid after vitrectomy surgeries for refractory retinal diseases.

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.

Role of Caveolin-1 for Blocking the Epithelial-Mesenchymal Transition in Proliferative Vitreoretinopathy.

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.

Better Visual Outcome by Intraocular Lens Ejection in Geriatric Patients with Ruptured Ocular Injuries.

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.

An Endovascular Cannulation Needle with an Internal Wire for the Fragmentation of Thrombi in Retinal Vein Occlusion.

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.

Development of a Fiber-Optic Optical Coherence Tomography Probe for Intraocular Use.

PURPOSE: To evaluate the performance of a newly developed 23-G optical coherence tomography (OCT) probe in animal and human eyes. METHODS: The 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. RESULTS: The 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. CONCLUSIONS: The 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.

Increased Ocular Levels of MicroRNA-148a in Cases of Retinal Detachment Promote Epithelial-Mesenchymal Transition.

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.

Restoration of Cone Interdigitation Zone Associated With Improvement of Focal Macular ERG After Fovea-Off Rhegmatogenous Retinal Reattachment.

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.

Effect of blue light-filtering intraocular lens on color vision in patients with macular diseases after vitrectomy.

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.

Buckling surgery and supplemental intravitreal bevacizumab or photocoagulation on stage 4 retinopathy of prematurity eyes.

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.

High osmolarity effect of intravitreal plasmin enzyme on rabbit retina.

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.

Changes in vitreous temperature during intravitreal surgery.

PURPOSE: To determine how different intraoperative surgical procedures affect the midvitreous temperature. METHODS: The 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. RESULTS: The 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. CONCLUSIONS: Our results showed that vitreous temperatures vary during different vitrectomy procedures.

Influence of preoperative intravitreal bevacizumab on visual function in eyes with proliferative diabetic retinopathy.

PURPOSE: Although bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), is effective in treating ocular neovascularization, there are some concerns about whether blocking VEGF might be harmful to retinal neurons. The purpose of this study was to evaluate the effects of preoperative intravitreal bevacizumab (IVB) on the visual function of eyes with proliferative diabetic retinopathy (PDR). METHODS: Thirty eyes of 23 patients (13 men and 10 women) with PDR who were treated at the Nagoya University Hospital from November 2006 to October 2009 were studied. All of the eyes were treated with 1.25 mg/0.05 ml of IVB 2-8 days before the vitrectomy. The protocol was approved by the Institutional Review Board of Nagoya University, and a written informed consent was obtained from each patient. All of the eyes had an active proliferative membrane with vitreous hemorrhage, but the fundus was visible. The mean age of the patients was 41.6 ± 10 years (range, 27-59), and the mean follow-up period was 9.7 ± 8.9 months (range, 1-24) after the vitrectomy. The visual acuity (VA) was measured, the visual fields were determined by Goldmann perimetery, and full-field electroretinograms (ERGs) were recorded before IVB, and before and after the vitrectomy. Fluorescein angiography was also performed before and after IVB. The area of the visual field was measured using a computer software (Scion Image). RESULTS: All eyes showed a regression of the new vessels and a reduction of fluorescent leakage from the new vessels after IVB. In addition, there was less bleeding during the removal of the proliferative membrane. The average VA was improved postoperatively from 20/250 to 20/70. However, there was no significant change in the amplitudes of the a- (from 261.4 to 259.2 µV) and b-waves (from 256.9 to 253.3 µV) of the ERGs, and there was no significant change in the visual field area after the surgery (from 8,322.5 to 7,496.3 degrees(2)). No significant ocular or systemic adverse events were observed. CONCLUSION: IVB-assisted vitrectomy led to an improvement of the VA in eyes with PDR without significant adverse events. There was no change in the visual fields and ERGs. Although only a small number of patients were studied, we conclude that IVB is most likely not harmful to retinal neurons if bevacizumab is washed out in less than 1 week. In addition, preoperative IVB made the surgery much easier by decreasing the activity of new vessels.

Acute retinal necrosis after corticosteroid pulse therapy for unilateral vogt-koyanagi-harada disease.

PURPOSE: To report on a patient with unilateral Vogt-Koyanagi-Harada (VKH) disease who developed varicella zoster-associated acute retinal necrosis after corticosteroid pulse therapy for the VKH disease. METHODS: Observational case report. RESULTS: A 36-year-old Japanese man was diagnosed with incomplete VKH disease despite having only unilateral changes. After corticosteroid pulse therapy, the same eye developed acute retinal necrosis. Polymerase chain reaction of an aqueous humor specimen showed DNA of the varicella zoster virus. Seven days after intravenous acyclovir, the retinitis disappeared. CONCLUSION: We encountered a rare case of unilateral VKH disease that developed acute retinal necrosis during corticosteroid pulse therapy. Acute retinal necrosis can develop during corticosteroid pulse therapy for VKH disease.

Triamcinolone-assisted removal of internal limiting membrane enhances the effect of vitrectomy for diabetic macular edema.

PURPOSE: To evaluate the efficacy of internal limiting membrane (ILM) peeling during vitrectomy to treat diabetic macular edema (DME). METHODS: In this nonrandomized study, we retrospectively analyzed the medical charts of 107 eyes that had undergone three-port vitrectomy to treat DME. The ILM was peeled in 65 eyes and not peeled in 42 eyes (ILM ON group). Indocyanine green (ICG) was used on 36 eyes (ICG group) and triamcinolone acetonide (TA) on 29 eyes (TA group) to make the ILM more visible. RESULTS: In all groups, the mean foveal thickness was significantly decreased after surgery. Visual acuity (VA) improved gradually after the surgery and was significantly better than the preoperative VA at 6 months in the ICG group and at 3 months in the TA group. Compared with the ILM ON group eyes, the eyes in the TA group had significantly better improvement of VA. CONCLUSION: TA-assisted ILM peeling may improve the VA outcome to treat DME.

Comparison of macular hole surgery without internal limiting membrane peeling to eyes with internal limiting membrane peeling with and without indocyanine green staining: three-year follow-up.

BACKGROUND: To compare the long-term anatomical closure rates and visual acuity after vitrectomy for macular hole (MH) surgery with and without internal limiting membrane (ILM) peeling and with and without indocyanine green (ICG) staining. METHODS: A total of 75 eyes of 71 patients with MH that had undergone vitrectomy were retrospectively studied. Group A consisted of 21 eyes that had vitrectomy without ILM peeling, Group B consisted of 38 eyes that had vitrectomy with ILM peeling without the ICG staining, and Group C consisted of 16 eyes that had vitrectomy with ILM peeling with ICG staining. The main outcome measures were the anatomical closure rates and visual acuities at 1, 2, and 3 years after surgery. RESULTS: MH were closed in all 75 eyes after the initial surgery. The visual acuity improved significantly (p < 0.0005) at 1 year after surgery and did not change significantly at 2 and 3 years after surgery in the 3 groups. Differences in the mean visual acuity in the 3 groups were not significant at 1, 2, and 3 years after surgery. CONCLUSIONS: These results suggest that ILM peeling or the use of ICG dye do not significantly affect the MH closure rates and the long-term visual acuities.