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Purpose: To evaluate the efficacy of switching from intravitreal antivascular endothelial growth factor (VEGF) agents to triamcinolone acetonide (TA) in eyes with diabetic macular edema (DME) or with retinal vein occlusion-associated macular edema (RVO-ME) on the resolution of the macular edema (ME)., Methods: The medical records of 11 eyes of 11 patients with DME and 9 eyes of 9 patients with RVO-ME whose MEs were refractory to anti-VEGF treatment were reviewed. The central retinal thickness (CRT), best-corrected visual acuity (BCVA), intraocular pressure (IOP), and the mean interval of the recurrences were measured during the anti-VEGF treatment and after switching to the TA injections., Results: Switching to TA injections significantly increased the mean interval for recurrences from 9.2 ± 2.7 weeks to 22.3 ± 12.9 weeks in eyes with DME ( P = 0.006). In eyes with RVO-ME, the mean period of recurrence was 12.3 ± 5.6 weeks before and 11.6 ± 4.4 weeks after the switch ( P = 0.44). The mean interval for recurrence was extended to more than 8 weeks in 7 of 11 eyes with DME, but none of the eyes with RVO-ME had a prolongation of more than 4 weeks. An elevation of the IOP was observed in 3 of the 20 eyes after the TA injection., Conclusions: These findings indicate that switching to TA injections can be a good option for DME eyes refractory to anti-VEGF injections but not for the RVO-ME eyes., Competing Interests: The authors have no proprietary interest in the materials used in this study., (Copyright © 2020 Tomoaki Tatsumi et al.)

Purpose: To measure the vascular density (VD) of the retinal capillary plexuses by optical coherence tomography angiography (OCTA) after surgery for an idiopathic macular hole., Methods: Retrospective, observational case series.Sixteen eyes of 16 patients with an idiopathic macular hole underwent vitrectomy with internal limiting membrane peeling. The VDs of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were determined by OCTA, and the retinal sensitivity (RS) and the inner retinal thickness (IRT) were measured before, and at 3, 6, and 12 months after the surgery. The VD, RS, and IRT were measured at the four parafoveal quadrants., Results: The mean age was 68.9 years. The VDs of the SCP and DCP were significantly correlated with the RS and IRT at 12 months postoperatively (all P < 0.001 for both SCP and DCP). The VDs of the SCP and DCP were higher, the RS more sensitive, and the IRT thicker in the nasal than the temporal quadrant at 12 months (P < 0.001, <0.001, =0.009, <0.001, respectively)., Conclusion: The significant correlation between the VDs of the SCP and DCP and the RS and IRT may be due to the nasal shift of the posterior retina.

Purpose: We compared the efficacy of sub-Tenon triamcinolone acetonide (STTA) to intravitreal triamcinolone aceto-nide (IVTA) injections during cataract surgery (CS) for patients with diabetic macular edema (DME)., Methods: The medical records of 33 eyes (26 patients) with DME which had undergone CS with STTA were compared to those of 34 eyes (27 patients) with DME which had undergone CS with IVTA. Central foveal thickness and best-corrected visual acuity (BCVA) were measured at the baseline and 1, 3, and 6 months after the surgery., Results: The BCVAs after STTA and IVTA were significantly improved at 3 and 6 months. Thirteen eyes in the IVTA group and 21 eyes in the STTA group required other therapies (p < 0.05). One case developed intraocular pressure elevation after IVTA and underwent selective la ser trabeculoplasty., Conclusions: Ophthalmologists should consider the merits and demerits of IVTA and STTA for DME treatment after CS., (© 2018 S. Karger AG, Basel.)

Purpose: To determine the relationship between preoperative and postoperative characteristics and visual outcomes after successful surgery for unclosed macular hole (MH)., Methods: The medical charts of 166 eyes of 161 patients who underwent vitrectomy for a MH were reviewed. The MH was not closed in 9 eyes of 9 patients after the initial surgery. The second vitrectomy with additional internal limiting membrane (ILM) peeling and gas tamponade was performed. The preoperative and postoperative best-corrected visual acuity (BCVA), optical coherence tomographic images, MH size, duration of MH before the first operation, and area of ILM peeling were studied., Results: The MH was closed in all eyes after the second surgery. The BCVA significantly improved from 0.77 to 0.25 logMAR units (20/118 to 20/36, p = 0.002). The postoperative subfoveal ellipsoid zone (EZ) was distinct and continuous in 3 eyes with good visual recovery. The final BCVA was not significantly correlated with the baseline characteristics and area of ILM peeling but was correlated with the postoperative status of the EZ., Conclusions: All MHs were closed and the mean postoperative visual acuity was significantly improved. The reason for poor visual recovery was the reduced microstructural recovery after the second surgery.

Purpose: To determine the size of the superficial foveal avascular zone (FAZ) by optical coherence tomography angiography before and after surgery for an idiopathic macular hole., Methods: A retrospective, observational case series, in which 16 eyes of 16 patients with an idiopathic macular hole were studied. Pars plana vitrectomy was performed with internal limiting membrane peeling. The foveal retinal vasculature was examined by optical coherence tomography angiography, and the area of the superficial FAZ was determined before, and at 1 and 3 months after the surgery. The area of the macular hole was also measured in the en face optical coherence tomography images. The central foveal thickness was measured to determine the relationship between the size of the superficial FAZ and foveal shape. The unaffected fellow eyes were used as controls., Results: The mean age of the patients was 68.9 years. The average preoperative superficial FAZ area was 0.45 ± 0.14 mm, which was significantly reduced to 0.23 ± 0.08 mm at 1 month (P < 0.001) and 0.25 ± 0.08 mm at 3 months postoperatively (P < 0.001). The size was smaller than that of the control eyes (0.36 ± 0.12 mm, P = 0.003). There was a significant inverse correlation between the area of the postoperative superficial FAZ and the central foveal thickness (r = -0.589, P = 0.016). The correlations between the visual acuity and the area of the superficial FAZ at 1 and 3 months postoperatively were not significant (P = 0.369 and 0.285)., Conclusion: The significant decrease in the superficial FAZ after the macular hole surgery indicates that there was a centripetal movement of the foveal tissue postoperatively.

Background/purpose: To determine the relationship between the alterations in the preoperative morphology of the retinal pigment epithelium (RPE) and the postoperative recovery after surgery to close an idiopathic macular hole (MH)., Methods: Retrospective interventional case series. Fifty-nine eyes of 59 patients with an idiopathic MH were studied. Pars plana vitrectomy was performed with the removal of the internal limiting membrane. The best-corrected visual acuity was measured, and the retinal morphology, including the presence of small RPE protrusions at the bottom of MH, was determined by spectral domain optical coherence tomography before and at 1, 3, and 6 months postoperatively., Results: The mean age of the patients was 66.7 years. Forty eyes (68%) had preoperative alterations of the RPE. The minimal (P < 0.001) and the base (P < 0.001) diameters of the MH were significantly larger in eyes with preoperative RPE alterations. The best-corrected visual acuity was significantly worse at baseline (P = 0.014) and at 6 months postoperatively (P = 0.048) in the eyes with RPE alterations. The defect of the ellipsoid zone was significantly longer in eyes with baseline RPE alterations at 1, 3, and 6 months postoperatively (P < 0.001, P = 0.001, and P = 0.032)., Conclusion: The presence of RPE protrusions at baseline was significantly correlated with slower morphologic recovery and poorer visual acuity after MH closure.

Aims: To determine whether there is a significant correlation between the peripapillary retinal thickness (pRT) and the serum level of vascular endothelial growth factor (VEGF) in patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome., Methods: This was a cross-sectional, observational case series. We studied 34 eyes of 17 treatment-naïve patients with POEMS syndrome whose intracranial pressure was within the normal range. The spectral-domain optical coherence tomographic (SD-OCT) examinations consisted of circle scans of 3.45 mm diameter around the optic disc. The pRT was automatically measured in the SD-OCT images and was used for the statistical analysis. The serum level of VEGF was measured by ELISAs, and the correlation between the pRT and the serum level of VEGF was determined. Multivariable logistic regression analyses were used to identify independent factors that were correlated with the pRT., Results: There was a significant positive correlation between the serum levels of VEGF and the average pRT of the two eyes of each patient (r=0.81, p<0.0001). There was a significant correlation between the pRT of the right and left eyes with an intraclass correlation coefficient of 0.839. Multiple regression analysis showed that the serum levels of VEGF were independent contributors to the pRT (standard regression coefficient=0.59, p=0.012)., Conclusions: The significant correlation between the pRT and the serum level of VEGF suggests that the higher serum level of VEGF might be associated with the development of the optic disc oedema in patients with POEMS syndrome., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Purpose: To compare the effects of sub-Tenon's capsule triamcinolone acetonide (STTA) injection to that of STTA injection combined with microaneurysm photocoagulation (MAPC; STTA + MAPC) on eyes with diabetic macular edema (DME)., Patients and Methods: The medical records of 138 eyes of 138 patients with DME treated by either STTA or STTA + MAPC were reviewed. The degree of DME was determined by the optical coherence tomographic features: patients with serous retinal detachment (SRD+; 38 eyes) and patients without SRD (non-SRD; 100 eyes). The central macular thickness (CMT) and the best-corrected visual acuity (BCVA) were measured periodically for 6 months after the treatments., Results: The BCVA was significantly improved in the non-SRD group after STTA + MAPC. The CMT was significantly improved in all groups and improved considerably more in the non-SRD group than in the SRD+ group after STTA + MAPC., Conclusion: Our findings indicate that MAPC has an additive effect in the non-SRD type.

We were presented with two cases of relapsing polychondritis (RP) associated with different types of ocular inflammation. The first case was a 35-year-old man who had bilateral hyperemic conjunctiva and ocular pain, and was referred to Chiba University Hospital with a diagnosis of episcleritis refractory. He was treated with dexamethasone eye drops. He developed tinnitus, deafness in both ears, and left auriculitis. A left auricular biopsy showed an infiltration of lymphocytes surrounding the cartilage. He was diagnosed with RP and treated with 30 mg/day oral prednisolone. After tapering the prednisolone, the scleritis in both eyes improved. The second case was a 71-year-old man who was deaf in both ears and had bilateral scleritis. At the first visit to our hospital, his left eyelid and right auricula were reddish and swollen, and he reported some pain. He was treated with intravenous antibiotics, and the left orbital cellulitis quickly improved. However, he developed right scleritis and left gonitis. Magnetic resonance imaging showed bilateral posterior scleritis and right auricular perichondritis. Auricular biopsy showed an infiltration of lymphocytes into the periauricular tissue. He was diagnosed with RP, and 40 mg/day oral prednisolone was given and his symptoms improved. Although RP is rare, it is a life-threatening disease. Thus, ophthalmologists should consider RP in patients with both ocular and auricular inflammation.

To determine the effect of advanced glycation end-products (AGEs) on neurite regeneration, and also to determine the regenerative effects of different neurotrophic factors (NTFs) on rat retinal explants, the retinas of SD rats were cultured in three-dimensional collagen gels and incubated in 6 types of media: (1) serum-free control culture media; (2) 100 μg/mL AGEs-BSA media; (3) AGEs-BSA + 100 ng/mL neurotrophin-4 (NT-4) media; (4) AGEs-BSA + 100 ng/mL hepatocyte growth factor media; (5) AGEs-BSA + 100 ng/mL glial cell line-derived neurotrophic factor media; or (6) AGEs-BSA + 100 µM tauroursodeoxycholic acid media. After 7 days, the number of regenerating neurites was counted. The explants were immunostained for nuclear factor-κB (NF-κB) and specificity protein 1 (SP1). Statistical analyses were performed by one-way ANOVA. In retinas incubated with AGEs, the numbers of neurites were fewer than in control. All of the NTFs increased the number of neurites, and the increase was more significant in the NT-4 group. The number of NF-κB and SP1 immunopositive cells was higher in retinas exposed to AGEs than in control. All of the NTFs decreased the number of NF-κB immunopositive cells but did not significantly affect SP1 expression. These results demonstrate the potential of the NTFs as axoprotectants in AGEs exposed retinal neurons.

Purpose: We report a case of unilateral blindness due to ophthalmic artery occlusion following injection of hyaluronic acid into the glabellar area for facial soft-tissue augmentation., Case: A 20-year old woman underwent injection of hyaluronic acid into the glabellar area at an aesthetic plastic clinic. Immediately after injection, she suffered nausea, pain, paralysis of limbs and visual loss in her right eye. Hyaluronidase was instanly injected into the same place, but these symptoms did not improve. She was transferred to our hospital's emergency department. At the first examination, she had no light perception in the right eye and her right pupil was dilated. The fundus examination revealed right central artery occlusion. No significant findings were detected in her head. Eye ball massage, hyperbaric oxygen therapy, and drip infusion of urokinase were conducted, but no improvement resulted. Fluorescein and indocyanine green angiography showed no filling of the right retinal and choroidal arteries. Electroretinogram was completely disappeared. Magnetic resonance angiography could not reveal the obstruction point of the ophthalmic artery., Conclusion: Ophthalmic artery occlusion was believed to have occured after injection of hyaluronic acid into the glabellar area.

Purpose: To compare the surgical outcomes during pars plana vitrectomy (PPV) for diffuse diabetic macular edema (DME) with pretreatment to those without pretreatment., Methods: The medical charts of 43 eyes of 46 patients who underwent PPV for DME were reviewed. The previously treated (Prev. Tx) group included 19 eyes of 20 patients who were pretreated with intravitreal bevacizumab, sub-Tenon injection of triamcinolone acetonide, and/or subthreshold micropulse diode laser photocoagulation before the PPV. The treatment naïve (Tx.Naïve) group included 24 eyes of 26 patients who underwent PPV alone. The central macular thickness (CMT) and best-corrected visual acuity (BCVA) were measured before treatment and 1, 3, and 6 months after., Results: In both groups, BCVA at 3 and 6 months and CMT at 1 month or later were significantly better than preoperative visual acuity. CMT at 1 month or later significantly decreased from the preoperative value (p<0.05). The differences in the BCVA and CMT between the Prev. Tx and Tx.Naïve group were not significant., Conclusions: PPV either with or without preoperative treatments can significantly improve the BCVA and reduce the CMT in patients with diffuse DME.

Purpose: To determine the relationship between the retinal thickness and sensitivity of the macular region after successful reattachment of an acute macula-off rhegmatogenous retinal detachment (RRD)., Methods: Twenty-three eyes of 23 patients with an acute macula-off RRD were studied (17 men, 6 women). The mean age of the patients was 53.2±14.7 years with a range from 20 to 73 years. The interval between the decrease in vision and surgery was <14 days in all cases. At 3 and 6 months after the surgery, the thickness of the inner and outer retina was determined by spectral-domain optical coherence tomography, and the retinal sensitivity was measured by microperimetry with MP-1. The values were compared to those obtained from the unaffected fellow eyes. Changes in the best-corrected visual acuity (BCVA), retinal thickness, and retinal sensitivity at 3 and 6 months from the baseline values were studied., Results: Ten eyes were treated by scleral buckling (SB) and 13 eyes by pars plana vitrectomy (PPV), and the retina was reattached in all eyes. The mean BCVA was significantly improved at 3 and 6 months postoperatively (p<0.001, <0.001). The outer retina of macula was significantly thicker after SB than after PPV (p=0.023 at 3 months; p=0.045 at 6 months). The retinal sensitivity of the central 10 degrees of the retinas after SB was lower than that of eyes after PPV (p=0.029 at 3 months and p=0.008 at 6 months)., Conclusions: The delay in the recovery of outer retinal thickness may be the cause of the lower sensitivity of the macula.

Purpose: To examine the effects of macular ischemia after intravitreal bevacizumab (IVB) in patients with diabetic macular edema(DME)., Methods: Thirty-three eyes of 33 patients with DME were treated with IVB. Fluorescein angiography (FA) was conducted before and 3 months after IVB, the pretreatment sizes of the foveal avascular zone (FAZ) calculated by FA were compared to the values at 3 months after IVB. This study was approved by the Chiba University Hospital Clinical Research Ethics Committee., Results: After IVB, the size of the FAZ enlarged significantly (p = 0.03). Among the 33 patients treated with IVB, 2 patients (6%) had advanced macular ischemia with an FAZ enlarged by 50% or more. In both patients, the visual acuity did not worsen and the foveal thickness decreased., Conclusions: It is possible that IVB led to macular ischemia.

Purpose: To investigate the effect of c-fos on apoptotic cell death and regeneration of damaged retinal ganglion cells (RGCs) in tissue culture of retinal explants., Methods: Retinas from transgenic mice carrying the exogenous c-fos gene under the control of the interferon (IFN)-alpha/beta inducible Mx-promoter (Mx-c-fos), c-fos-deficient mice, and littermate control mice were dissected and cultured in a three-dimensional collagen gel culture system, followed by an analysis of TdT-dUTP terminal nick-end labeling (TUNEL) staining and measurement of neurites that emerged from explants., Results: Compared with littermate control mice, Mx-c-fos transgenic animals showed a higher ratio of TUNEL positivity in the RGC layer from early in the culture period that correlated with the small number of regenerating neurites. In contrast, the c-fos-null mutated mice showed a still-lower ratio of TUNEL-positive cells. Nevertheless, the number of regenerating neurites was significantly lower in the initial phase, although the drastic increase in density of neurite regeneration was observed in the late period of culture., Conclusions: These findings suggest that c-fos is involved in both apoptotic cell death and regeneration of damaged RGCs. Elucidation of the precise c-fos-mediated cascade involved in RGC apoptosis and regeneration is significant in realizing neuronal survival and regeneration.

Purpose: To determine whether the brain-derived neurotrophic factor (BDNF) gene can be transfected into retinal ganglion cells (RGCs) by electroporation and whether axotomized RGCs can be rescued after transfection by BDNF in adult rats., Methods: Mouse BDNF cDNA was injected intravitreally followed by in vivo electroporation in adult rats. The expression of BDNF in RGCs was confirmed by Western immunoblot analysis and immunohistochemistry. After introduction of BDNF cDNA, the survival of axotomized RGCs was estimated by the TdT-dUTP terminal nick-end labeling (TUNEL) method and measured by counting the number of RGCs that were labeled retrogradely by 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyamine percholorate (diI) applied to the superior colliculus (SC)., Results: Eyes with injection of the BDNF gene followed by in vivo electroporation showed a significantly higher level of expression of BDNF in the RGC layer, a higher rescue ratio, and a lower number of TUNEL-positive cells than the control samples., Conclusions: These findings demonstrate that electroporation is an effective method for the direct delivery of genes into RGCs, and that the BDNF gene transferred into RGCs by in vivo electroporation can protect axotomized RGCs against apoptosis.