Search

Purpose: To evaluate the long-term efficacy and safety of ripasudil-brimonidine fixed-dose combination (RBFC), a new intraocular pressure (IOP)-lowering medication for glaucoma and ocular hypertension (OHT)., Methods: This prospective, multicentre (23 sites in Japan), open-label study enrolled patients with primary open-angle glaucoma (POAG), OHT or exfoliative glaucoma and assigned them to one of four combination therapy cohorts, based on previous treatment(s) received: prostaglandin (PG) analogue (Cohort 1); PG analogue and beta-adrenoceptor blocker (β-blocker) (Cohort 2); PG analogue, β-blocker and carbonic anhydrase inhibitor (Cohort 3); or other/no treatment (Cohort 4). After a ≥ 4-week screening period, eligible patients received twice-daily RBFC for 52 weeks in addition to the treatments they were already receiving. Efficacy was assessed by change in IOP from baseline through week 52. Adverse events and adverse drug reactions (ADRs) were monitored throughout., Results: In total, 179 patients from Cohort 1 (n = 48), Cohort 2 (n = 44), Cohort 3 (n = 41) and Cohort 4 (n = 46) entered the RBFC treatment period. For all cohorts, mean IOP was significantly reduced at 11:00 (2 h after instillation of RBFC) through week 52 with the changes from baseline at week 52 of - 2.7 to - 4.1 mmHg across cohorts; all p < 0.001. Common ADRs were conjunctival hyperaemia (58%), allergic conjunctivitis (18%) and blepharitis (17%), most of which were mild in severity., Conclusion: These data demonstrated the long-term efficacy and safety of RBFC, both alone and in combination with other anti-glaucoma agents. RBFC may offer a new treatment option for the long-term management of glaucoma and OHT., Trial Registration: Japan Registry of Clinical Trials Identifier: jRCT2080225063., Date of Registration: 17 February 2020., (© 2024. The Author(s).)

Purpose: To explore the features of filtering blebs exhibiting transconjunctival oozing via three-dimensional anterior segment optical coherence tomography (3D AS-OCT)., Methods: In this cross-sectional study, 131 eyes of 131 patients exhibiting filtering blebs were examined. Of those, 20 eyes were excluded as flat-shaped, non-functioning bleb. Transconjunctival oozing was defined as transconjunctival aqueous egress evident on the bleb surface, in the absence of any point leak observable using a slit-lamp, as confirmed by application of digital pressure. Total bleb height, the height of the fluid-filled cavity, and bleb wall thickness and density were measured using 3D AS-OCT. Patient age, the etiology of glaucoma, postoperative follow-up period, number of glaucoma medication classes prescribed, intraocular pressure (IOP), grade of bleb vascularity, and bleb parameters were compared in eyes with and without bleb oozing., Results: Sixty (54.0 %) of 111 eyes excluding non-functioning flat blebs exhibited oozing; mean IOP value (11.7 ± 4.5 vs. 14.8 ± 4.0 mmHg) and bleb vascularity grade (1.5 ± 0.7 vs. 2.4 ± 1.0) were lower than those of eyes without oozing. Total bleb height (1.1 ± 0.4 vs. 0.9 ± 0.4 mm), bleb wall thickness (0.7 ± 0.4 vs. 0.5 ± 0.3 mm), and bleb wall density (131.3 ± 45.7 vs. 180.9 ± 39.8 optical density units) differed significantly between the two groups (oozing vs. non-oozing)., Conclusion: Transconjunctival oozing after trabeculectomy with MMC was associated with a low IOP, low-level bleb vascularity, an elevated total bleb height, a thicker bleb wall, and low bleb wall density.

Aims: To evaluate long-term efficacy of goniosynechialysis (GSL) combined with phacoemulsification and intraocular lens implantation (phaco-GSL) for primary angle closure or primary angle-closure glaucoma (PAC/PACG) and to analyze risk factors for surgical outcomes., Methods: We reviewed medical records of 109 eyes of 109 patients (mean [± SD] age 70 ± 9.4 years) who underwent phaco-GSL as primary treatment of PAC/PACG at five institutions. All eyes had a preoperative intraocular pressure (IOP) of ≥ 21 mmHg with or without medications. Surgical failure was defined as: (1) condition A: persistent IOP values of ≥ 21 mmHg, or (2) condition B: IOP values of ≥ 18 mmHg, with or without topical ocular medication, at two consecutive follow-up visits, or additional operations needed. Risk factors for surgical failure were analyzed via Cox proportional hazards model., Results: Mean follow-up was 40.0 months (range, 1 to 139 months). Probabilities of treatment success at 1 and 3 years after phaco-GSL were 85.9 % and 85.9 % (condition A) and 66.2 % and 61.0 % (condition B) respectively. Via multivariable analysis, we identified risk factors for surgical failure to be younger age (relative risk [RR] = 0.93/year, P = 0.0333) and absence of postoperative laser peripheral iridoplasty (LPI) (P = 0.0359) for condition A, and younger age (RR = 0.94/year, P = 0.0035), lower preoperative IOP (RR = 0.93/mm Hg, P = 0.0131), and absence of postoperative LPI (RR = 2.34, P = 0.0228) for condition B., Conclusions: The outcome of phaco-GSL for PAC/PACG may depend on age, preoperative IOP, and postoperative LPI.

Background: To compare 12-month results of two single initial treatments--photodynamic therapy with verteporfin alone (PDT group), and this therapy combined with intravitreal bevacizumab (IVB) (COMB group)--for neovascular age-related macular degeneration (AMD), not including patients with polypoidal choroidal vasculopathy (PCV) who were presumed to have AMD., Methods: This retrospective study evaluated 23 eyes in the PDT group and 22 eyes in the COMB group. IVB (1.25 mg) was administered within 2 weeks after PDT. Main outcome measures were best-corrected visual acuity (VA), central foveal thickness by optical coherence tomography, and number of treatments., Results: At month 12, the PDT group had gained 0.7 letter mean VA and the COMB group, 8.8 letters (P = 0.04). Ten eyes (43%) in the PDT group and 19 eyes (86%) in the COMB group received only one treatment, and significant difference was found (P = 0.005). No severe ocular or systemic safety concerns were discovered., Conclusions: Our 12-month results of PDT combined with IVB for Japanese patients with AMD without PCV appeared to be more effective than those of PDT alone with fewer treatments.

Purpose: To evaluate the effects of radial conjunctival incision during fornix-based trabeculectomy, and conjunctival scarring associated with previous ocular surgeries, for the restriction of bleb formation., Methods: Digital photo-slit lamp images of filtering blebs, which had undergone fornix-based trabeculectomy with mitomycin C previously, were analysed. The area and the height of the bleb in the conjunctivae with radial incision (Ain and Hin, respectively) were compared with the area and the height of the bleb in the conjunctivae without radial incision (Ano and Hno, respectively). We compared the parameters of bleb area (total bleb area, Ain and Ano) and bleb height (the bleb height at the centre of the scleral flap; Hc, Hin and Hno) in eyes without previous ocular surgeries, with those in eyes that underwent previous ocular surgeries., Results: The study population consisted of 51 eyes. The Ano and the Hno were significantly larger than the Ain (p < 0.001) and the Hin (p < 0.001) respectively. Subgroup analyses in eyes without previous ocular surgeries and eyes with phacoemulsification cataract surgery also showed that the Ano was significantly larger than the Ain. However, there was no significant difference between the Ano and the Ain in eyes with previous trabeculectomy. A comparison of bleb formation between eyes without previous ocular surgeries and eyes with cataract surgery showed no significant differences in each of the bleb area and bleb height parameters. By contrast, the total bleb area (p = 0.021), the Ano (p = 0.017) and the Hc (p = 0.045) were significantly smaller in eyes with previous trabeculectomy than in eyes without previous ocular surgeries., Conclusions: Our data demonstrate that bleb formation depends on radial conjunctival incision during fornix-based trabeculectomy and surgical conjunctival scarring from previous trabeculectomy.

Purpose: To map neural crest cell fate during eye development., Methods: Neural crest cells were tracked in developing mouse eyes using a transgene expressing Cre recombinase controlled by the Protein 0 promoter and a Rosa26 Cre-responsive reporter gene that produced beta-galactosidase after Cre-mediated recombination., Results: beta-galactosidase-positive cells were detected in the periocular segment on embryonic day (E) 9.5. Several neural crest cell-derived tissues including corneal stroma, corneal endothelium, iridocorneal angle, ciliary body, primary vitreous and eyelid were strongly stained on E13.5-E18.5. The staining decreased in the corneal stroma after birth, but persisted in the presumptive iridocorneal angle., Conclusions: Protein 0-Cre transgenic mice offer a conditional knock-out strategy to investigate anterior eye segment differentiation.

Purpose: Transient retinal ischemia induces the death of retinal neuronal cells. Postischemic damage is associated with the infiltration of leukocytes into the neural tissue through vascular endothelia. The current study aimed to investigate whether this damage was attenuated by the inhibition of Rho/ROCK (Rho kinases) signaling, recently shown to play a critical role in the transendothelial migration of leukocytes., Methods: Y-27632, a selective inhibitor of ROCK, was injected intravitreally into rat eyes with transient retinal ischemia. Cell loss of the ganglion cell layer (GCL) and thinning of the inner plexiform layer (IPL) with and without the administration of Y-27632 were evaluated by histological analysis, TUNEL assay and retrograde labeling of retinal ganglion cells (RGCs). To examine the attenuation of leukocyte infiltration in postischemic retinas with the administration of Y-27632, silver nitrate staining and immunohistochemistry using an anti-LCA antibody were performed., Results: Cell loss of the GCL and thinning of the IPL were significantly attenuated when 100 nmol Y-27632 was administered within three hours of the induction of ischemia. TUNEL assay and retrograde labeling of RGCs showed a decreased number of apoptotic cells and an increased number of RGCs in Y-27632-injected retinas. Moreover, silver nitrate staining and immunohistochemical analysis using an anti-LCA antibody showed that Y-27632 injection dramatically inhibited leukocyte infiltration and endothelial disarrangement., Conclusions: Our data suggest that inhibition of Rho/ROCK signaling offers neuroprotective therapy against postischemic neural damage, by regulating leukocyte infiltration in the neural tissue.

Background: Physiologic pituitary enlargement during normal pregnancy is well known, but we are unaware of previous reports on a natural course of visual loss due to this disease., Methods: A 30-year-old woman presented blurred vision in the left eye from the 30th week of pregnancy. At 38 weeks visual acuity was 0.9 in the left eye. Automated perimetry revealed a mild central visual defect in the left eye. A magnetic resonance imaging (MRI) scan revealed pituitary enlargement with compression of the anterior optic chiasm. We observed the natural course of this case., Results: At 16 weeks after delivery, visual acuity was 1.5 in both eyes with normal visual field, and an MRI scan revealed a normal-sized pituitary without compression of the optic chiasm., Conclusions: Ophthalmologists should be aware of visual loss by physiologic pituitary enlargement to avoid unreasonable neurosurgical procedures.

Purpose: To evaluate quantitative choroidal dye filling velocity in patients with Vogt-Koyanagi-Harada disease (VKH) before and after corticosteroid treatment using indocyanine green (ICG) angiography., Methods: ICG angiography was performed in seven VKH patients before and after systemic corticosteroid treatment. Choroidal dye curves were obtained by image analysis software and analyzed using an exponential model. The model's time constant (tau) was used to evaluate choroidal dye filling velocity., Results: Compared with controls, acute phase choroidal tau values in VKH patients were significantly longer, suggesting choroidal circulation disturbance. During the recovery phase, choroidal tau values were significantly shortened, suggesting choroidal circulatory disturbance improvement., Conclusion: Choroidal dye filling velocity may be useful for VKH diagnosis and verification of corticosteroid treatment effectiveness.

Purpose: To evaluate the efficacy and safety of trans-Tenon's retrobulbar triamcinolone acetonide (TA) infusion for the treatment of refractory diabetic macular edema (DME) after vitrectomy., Methods: After topical anesthesia, 20 eyes from 20 patients with persistent DME after pars plana vitrectomy were treated with trans-Tenon's retrobulbar infusion of 40 mg TA through an inferotemporal approach. The mean duration (+/-SD) between vitrectomy and trans-Tenon's retrobulbar TA infusion was 11.4+/-7.9 months. The mean follow-up period (+/-SD) after trans-Tenon's retrobulbar TA infusion was 13.3+/-2.8 months., Results: At 1 week after trans-Tenon's retrobulbar TA infusion, the mean central retinal thickness (+/-SD) measured by optical coherence tomography was 381+/-99 mum, which was a statistically significant decrease in comparison with the preoperative thickness (555+/-112 mum) (P<0.001). Additional trans-Tenon's retrobulbar TA infusions were performed in ten eyes (50%), due to the recurrence of DME at 6.6+/-3.0 months after the first TA infusion. At the final examination, macular edema resolved in 13 (65%), improved in four (20%), and remained unchanged in three (15%) of the 20 eyes. At 1 month after trans-Tenon's retrobulbar TA infusion, the mean laser flare value (+/-SD) was 9.6+/-3.0 photon/ms, which was a statistically significant decrease in comparison with the preoperative value (15.5+/-5.9 photon/ms) (P<0.01). Furthermore, in ten eyes (50%) with recurrent DME, re-elevated laser flare values were observed prior to the recurrence of DME. The final best-corrected Snellen visual acuity improved by two or more lines in nine eyes (45%), and remained unchanged in 11 eyes (55.0%). IOP elevation equal to or higher than 21 mmHg was observed in three (15%) of the 20 eyes with TA infusion, and was controlled by topical medications. No other injection-related complications were observed., Conclusion: Trans-Tenon's retrobulbar TA infusion is an effective and safe method for the treatment of refractory DME, which is present even after vitrectomy.

Purpose: Description of cases of traumatic macular hole that appeared concomitant with a ruptured internal limiting membrane (ILM) that was apparent during vitrectomy only after staining with indocyanine green (ICG)., Methods: Vitrectomy with ILM peeling was performed on a 20-year-old man and a 13-year-old boy for treatment of traumatic macular holes., Results: During vitrectomy, the ILM was found to be ruptured along the area of an identified macular hole only after ICG staining. After the vitrectomy, the macular holes were closed and visual acuity improved. However, visual field defect associated with apparent inner-layer retinal damage remained., Conclusion: Blunt trauma can cause severe inner-layer retinal damage with rupture of the ILM as well as frank macular hole formation and choroidal rupture.

Purpose: To investigate the effects of subretinal indocyanine green (ICG) on retinal morphology in rabbit eyes., Methods: Retinal bleb detachments were produced by injections of ICG at dosages of 25 mg/ml, 5 mg/ml, and 0.5 mg/ml or with an injection of balanced salt solution (BSS) into the subretinal space of albino rabbit eyes. Morphological change was assessed by light and transmission electron microscopy from the viewpoint of dose and time. Some sections were also probed with the TUNEL technique to detect apoptotic cells., Results: At 14 days after subretinal injection of BSS and 0.5 mg/ml ICG, the structure of the retina was well preserved. However, injections of 5 mg/ml or 25 mg/ml caused thinning of the retina, especially loss of the outer retinal layer. In eyes injected with 5 mg/ml ICG, the photoreceptors began disappearing within 3 days after the injection and over time showed the development of retinal atrophy. TUNEL-positive cells appeared abundantly in the photoreceptor layers 1 and 3 days after the injection of 5 mg/ml ICG. Transmission electron microscopy confirmed apoptosis in the photoreceptors., Conclusion: These data indicate that subretinal ICG induces apparent morphological damage of the retina in a dose-dependent manner.

Purpose: To investigate the long-term histological changes in rabbit retina damaged by infusion air during vitrectomy., Methods: Fourteen eyes of 14 rabbits were used. A standard three-port vitrectomy with artificial posterior vitreous detachment followed by fluid-air exchange was performed. After the fluid-air exchange, one side port was kept open for 30 s to freely introduce the air into the vitreous cavity under a pressure of 40 mmHg. Four weeks after surgery, indocyanine green angiography and histological examination were performed., Results: At the air-infused area, indocyanine green angiography revealed the filling delay of the choroidal circulation in the early phase. The retinal surface was smooth and the internal limiting membrane was revealed to be intact by scanning electron microscopy. Light microscopy documented the thinning of the photoreceptor layer in the air-infused area. Transmission electron microscopy showed the disarrangement of the retinal pigment epithelium and loss of choriocapillaries., Conclusion: Infusion air during vitrectomy causes long-term outer retinal damage after surgery. Thinning of the photoreceptor cells, disarrangement of the retinal pigment epithelium and loss of choriocapillaries reflect the findings that we have observed previously in clinical cases. Visual field defect is a complication of vitreous surgery using fluid-air exchange. Although the visual field defects were observed just after surgery, abnormal fundus lesions continued to appear over time after the surgical procedure.

Background: To identify risk factors related to the onset of secondary glaucoma in eyes that have undergone pars plana lensectomy for congenital cataract., Methods: We investigated intraocular pressure levels after pars plana lensectomy for congenital cataract in 80 eyes of 44 patients who were followed up for at least 36 months. Mean age at the time of pars plana lensectomy was 11+/-18 months. Mean follow-up period was 116+/-57 months., Results: An elevation in intraocular pressure (>20 mmHg) was found in 21 eyes of 12 patients (26%). In 7 of these 21 eyes surgical treatment was required. The incidence of the coexistence of microcornea (or microphthalmos) with congenital cataract was significantly higher in the glaucoma group than that in nonglaucoma group. The final visual acuity in the nonglaucoma group was significantly better than that in the glaucoma group., Conclusion: Our results show the importance of careful follow-up of intraocular pressure after pars plana lensectomy for congenital cataract, especially when microcornea (or microphthalmos) is present.

Purpose: To determine whether clinical characteristics are correlated with increased levels of transforming growth factor-beta 2 (TGF-beta 2) in aqueous humor in glaucomatous eyes., Methods: Aqueous humor samples were collected from 91 glaucomatous eyes. Included were samples from primary open-angle glaucoma (POAG) in 40 eyes, (pseudo)exfoliation syndrome (EXS) in 18 eyes, primary angle-closure glaucoma (PACG) in 26 eyes and uveitis-related secondary glaucoma (SG) in 7 eyes. TGF-beta 2 in aqueous humor was assessed with a specific-capture ELISA., Results: The mean concentration (+/- standard error) of mature (biologically active) TGF-beta 2 in the aqueous humor of eyes with POAG was 293.6 +/- 33.6 pg/ml, significantly higher than that in eyes with PACG, EXS and SG: 147.5 +/- 28.1, 135.8 +/- 30.2 and 41.0 +/- 10.7 pg/ml, respectively (P = 0.0006, P = 0.0010 and P = 0.0003; analysis of variance). The mean concentration (+/- standard error) of total TGF-beta 2 in the aqueous humor of eyes with POAG was 1647.6 +/- 124.5 pg/ml, not significantly different from that in eyes with PACG, EXS and SG: 1482.9 +/- 148.2, 1442.7 +/- 187.8 and 1929.0 +/- 367.6 pg/ml, respectively. A multivariate analysis using logistic regression showed significant correlations between mature TGF-beta 2 concentration and history of cataract surgery (P = 0.0225) and the use of carbonic anhydrase inhibitors (P = 0.0143)., Conclusions: Our results indicate that increased levels of TGF-beta 2 may play an important role in the pathogenesis of POAG.

Background: We previously reported the effectiveness of goniosynechialysis and trabeculotomy ab externo for adult-onset glaucoma. In this study, we performed non-filtering surgery on patients with primary angle-closure glaucoma and studied the long-term outcome of this treatment., Methods: Included in this study were 35 eyes of 25 patients with primary angle-closure glaucoma, each of which had an intraocular pressure greater than 20 mmHg with maximal tolerated antiglaucoma medication, even after laser iridotomy or surgical iridectomy. Of these 35 eyes, 22 underwent trabeculotomy and 13 underwent goniosynechialysis. All patients were followed up for at least 18 months., Results: In 21 (95%) of 22 eyes after trabeculotomy, and in 12 (92%) of 13 eyes after goniosynechialysis, intraocular pressures were well controlled at or below 21 mmHg at the final examination. However, in two of the 21 eyes in which trabeculotomy was a success, and in four of the 12 eyes in which goniosynechialysis was successful, the procedure had to be repeated before adequate control of pressure was achieved., Conclusion: Our results show that intraocular pressure in most cases of primary angle-closure glaucoma can be controlled by restructuring of the physiologic aqueous outflow route by means of goniosynechialysis or trabeculotomy, and that filtering surgery is not necessary.

Goniosynechialysis (GSL) was performed in 70 eyes with primary angle-closure glaucoma in which the intraocular pressure (IOP) could not be controlled with laser or surgical iridectomy. Following GSL, the IOP was maintained at below 20 mmHg, with and without eye drops, in 34 (87%) of 39 aphakic eyes and in 13 (42%) of 31 phakic eyes. In 8 of 10 eyes, all of which were phakic and the first GSL procedure was not effective, IOP could be controlled by a second GSL procedure combined with lens extraction. Life-table analysis showed a significant difference between the probable success rate, after 5 years, between the phakic and aphakic groups. Postoperative tonographic C values showed improvement in outflow facility. However, frequently encountered complications were exudation of fibrin and minor hemorrhage. Our results suggest that a combination of GSL and extraction of the lens may be necessary to control refractory angle-closure glaucoma.

To evaluate the relationship between the papillomacular bundle defect and glaucoma types, abnormalities of the optic disc, distance between the disc and foveola, and axial length, we examined one eye of 82 patients with normal tension glaucoma, 117 patients with chronic high tension glaucoma, and 102 controls. Two types (diffuse and focal types) were found in the papillomacular bundle defect, and the former predominated. Eyes with a long axial length (P < 0.01), a diagnosis of normal tension glaucoma (P < 0.05), or a large optic disc (P < 0.05) tended to have diffuse-type papillomacular bundle defects, while eyes with a short axial length, a diagnosis of high tension glaucoma, or a large ovalness index are less likely to have it. Thus, a long axial length, a large optic disc, and normal tension glaucoma are risk factors for the diffuse-type papillomacular bundle defect.

We performed laser gonioplasty following goniosynechialysis on 12 eyes that exhibited a very narrow angle. In these cases, angle closure had recurred postoperatively, although gonioscopy carried out at the time of goniosynechialysis revealed opening of the trabecular meshwork. The use of laser gonioplasty following goniosynechialysis was most effective in flattening the configuration of the iris and opening the iridocorneal angle. The induced alteration of the structure of the iris remained unchanged in all cases throughout the follow-up period, and intraocular pressure remained below 20 mmHg in 9 of the 12 eyes. It thus appears that a combination of goniosynechialysis and laser gonioplasty may be effective in the management of refractory angle-closure glaucoma in the presence of an extremely narrow angle.