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Rho-associated protein kinase (ROCK), a ubiquitously expressed signaling messenger and downstream effector of Rho, is activated by several bioactive factors in the aqueous humor (AH). Rho-ROCK signaling regulates a wide spectrum of fundamental cellular events, including cell adhesion, motility, proliferation, differentiation, and apoptosis. Previous studies, including our own, found that ROCK inhibitor lowers intraocular pressure (IOP) via a direct effect on the conventional AH outflow pathway, by regulation of contractile properties, fibrotic activity, and permeability of the trabecular meshwork (TM) and Schlemm's canal (SC) tissues, influencing extracellular matrix (ECM) production. Recently, a novel ROCK inhibitor, ripasudil, has been introduced in Japan. Other ROCK inhibitors are now in clinical trials as new IOP-lowering drugs for glaucoma patients. To date, ripasudil, administered together with other glaucoma medications, has proved safe and efficient in lowering IOP as well as additional effects such as prostaglandin analogs, beta-blockers, and carbonic anhydrase inhibitors, all of which help lower IOP by different mechanisms. In addition, we found that long-term treatment with ripasudil exerted an additional IOP-lowering effect, especially in eyes with high IOP, suggesting that late-onset remodeling of the ECM in glaucomatous eyes may elicit mild and delayed changes in IOP levels. ROCK inhibitors have also shown several additional effects, including increased retinal blood flow, direct protection of neurons against various types of stress, and regulation of wound healing; these benefits may potentially be useful in glaucoma treatment.

Purpose: To evaluate the prognostic factors for surgical outcomes of subsequent trabeculectomy with mitomycin C (MMC) after prior incisional glaucoma surgery., Methods: We reviewed medical records of a total cohort of 781 trabeculectomies with MMC, and selected 125 patients (125 eyes). The primary endpoints included persistent intraocular pressure (IOP) of ≥21 or <5 mmHg, the need for additional glaucoma surgery and deterioration of visual acuity to no light perception. Univariate and Multivariate analyses were performed by using the Cox proportional hazards model., Results: The mean follow-up period was 26.8 months. The probabilities of success at 1, 2, and 3 years were 80.6, 72.2, and 70.6 %, respectively. Multivariate analysis showed that a shorter time interval between prior glaucoma surgery and subsequent trabeculectomy [relative risk (RR), 0.8867/year; P = 0.0090] and the number of prior trabeculectomies (RR, 2.2645; P = 0.0029) were significant prognostic factors for subsequent failure of trabeculectomy with MMC., Conclusion: A short time period between prior glaucoma surgery and subsequent trabeculectomy and the number of prior trabeculectomies are associated with surgical failure of subsequent trabeculectomy with MMC.

Purpose: To evaluate the prognostic risk factors for failure of trabeculectomy with mitomycin C (MMC) in vitrectomized eyes., Methods: Retrospective cohort study. We reviewed the medical records of 116 patients (116 eyes) treated at Kumamoto University Hospital. The primary endpoints were persistent intraocular pressure of >21 mmHg, deterioration of visual acuity to no light perception, or additional glaucoma procedures. Multivariable analysis was performed with the Cox proportional hazards model., Results: The mean follow-up period was 36.5 months (range, 0.5-134.1 months). The probability of success 1 year after trabeculectomy was 55.1 %, 2 years after was 45.3 %, and 3 years after was 43.1 %. The multivariable model showed that higher preoperative intraocular pressure (IOP) [relative risk (RR), 1.05/mmHg; P = 0.0077] and neovascular glaucoma (NVG) (RR, 1.88; P = 0.049) were prognostic factors for surgical failure., Conclusions: The prognostic factors for surgical failure of trabeculectomy with MMC in vitrectomized eyes are a higher preoperative IOP and NVG.

Purpose: To review the surgical results and complications of trabeculectomy techniques in patients with advanced glaucoma and threatened fixation., Methods: Trabeculectomy had been carried out on 49 advanced glaucoma patients (49 eyes) using mitomycin C and postoperative laser suture lysis. The clinical records prior to and 2 months after surgery were reviewed, and the long-term surgical outcomes were determined., Results: Two months after surgery there were no eyes with fixation loss. Intraocular pressure (IOP) levels were reduced from 22.8 +/- 6.0 to 11.7 +/- 4.7 mmHg. Kaplan-Meier survival analysis showed that the success rate in achieving IOPs of 15 mmHg or lower 5 years after surgery was 70%. The chance of visual acuity remaining within two lines of the preoperative level was 75%. In 29 of the 49 eyes, visual acuities remained at their preoperative level at the time of the final visit, but had decreased to less than 0.1 in three eyes (cataract progression, n = 2; fixation loss, n = 1)., Conclusion: The results suggest that laser suture lysis and stepwise management of IOP levels, which are performed as part of the modern postoperative management of trabeculectomy, decrease the frequency of fixation loss during the early postsurgical phase.

Purpose: A decrease in beta-amyloid(1-42) (Abeta42) and an increase in tau in the cerebrospinal fluid are reported to be characteristic phenomena in Alzheimer's disease patients. To test the idea that Abeta42 and tau contribute to the development of retinal diseases, we measured Abeta42 and tau concentrations in the vitreous fluid from patients with macular hole (n = 13), diabetic retinopathy (n = 15), or glaucoma concurrent with other ocular diseases (n = 8)., Methods: Vitreous samples were collected from patients who underwent vitrectomy, and sensitive and specific enzyme-linked immunosorbent assays were used to determine the concentrations of Abeta42 and tau., Results: By comparison with the levels in the control macular-hole patients (33.9 +/- 7.1 pg/ml for Abeta42; 3.3 +/- 3.2 pg/ml for tau), there was a significant decrease in the Abeta42 level and a significant increase in the tau level in patients with diabetic retinopathy (1.8 +/- 1.9 pg/ml for Abeta42, P = 0.002; 153.7 +/- 71.6 pg/ml for tau, P = 0.041) or glaucoma concurrent with other ocular diseases (2.8 +/- 1.8 pg/ml for Abeta42, P = 0.006; 113.6 +/- 43.1 pg/ml for tau, P = 0.023)., Conclusions: Our findings indicate the possibility of a role for Abeta42 and tau in the pathogenesis of some retinal diseases.

Purpose: To evaluate the corneal thickness following pars plana lensectomy for congenital cataracts., Methods: The corneal thickness was measured in 24 eyes of 24 patients with congenital cataracts who had undergone pars plana lensectomy at a mean age of 24 +/- 32 (SD) months. The mean age at the time of our evaluation was 15 +/- 3 years. These measurements were compared with those in 15 eyes of an age-matched group of 15 normal volunteers. The central corneal thickness and endothelium were evaluated in both groups., Results: The mean corneal thickness of the cataract-extracted eyes (592 +/- 47 micro m) was significantly greater than that of the controls (529 +/- 43 micro m; P < 0.001). There was no significant difference in the corneal endothelial cell count between cataract-extracted eyes (3420 +/- 715/mm(2)) and the controls (3182 +/- 358/mm(2); P = 0.49). However, there were significant differences in the frequency of hexagonally shaped endothelial cells (63% +/- 8.4%, cataract-extracted eyes; 70% +/- 7.7%, controls; P < 0.01), and in the coefficient of variation in the endothelial cell size (33 +/- 6.0, cataract-extracted eyes; 26 +/- 4.8, controls; P< 0.01)., Conclusion: The central cornea of congenital cataract-extracted eyes was significantly thicker than that of controls.

Purpose: The outcome of vitrectomy combined with phacoemulsification and intraocular lens implantation (PEA+IOL) for diabetic macular edema was evaluated., Methods: Included in this study were 31 patients (42 eyes) with clinically significant diabetic macular edema, in whom posterior vitreous detachment was not observed. Pars plana vitrectomy combined with PEA+IOL was performed on 15 eyes. Sixteen phakic eyes and 11 pseudophakic eyes were followed up without vitrectomy as controls. Visual acuity and the state of macular edema were evaluated., Results: After follow-up of 18 +/- 7 (mean +/- SD) months, clinically significant macular edema remained in 3 eyes (20%) of the vitrectomy group, in 11 eyes (69%) of the phakic control group, and in 9 eyes (82%) of the pseudophakic control group. The logarithm of the minimal angle of resolution (Log(MAR)) of the best-corrected visual acuity of the vitrectomy group eyes significantly improved from 1.09 +/- 0.27 to 0.80 +/- 0.35 (P <.01), while that of pseudophakic control eyes significantly decreased from 0.59 +/- 0.17 to 0.86 +/- 0.28 (P <.05). The Log(MAR) of phakic control eyes also decreased from 0.82 +/- 0.36 to 0.93 +/- 0.30, but there was no significant difference (P =.19)., Conclusion: Vitrectomy combined with PEA+IOL is an effective surgical modality to improve visual acuity in eyes with clinically significant diabetic macular edema.

Purpose: To elucidate the characterization of intraocular pressure (IOP) spike after trabeculotomy, and after the combined procedure of phacoemulsification and aspiration (PEA) and intraocular lens (IOL) implantation., Methods: Included in this study were 39 patients (53 eyes) with primary open-angle glaucoma with IOPs uncontrolled even with anti-glaucoma medication. We conducted a retrospective study for the following two groups: Patients who underwent trabeculotomy alone (25 eyes) and patients undergoing trabeculotomy combined with PEA and implantation of an IOL (28 eyes)., Results: In 7 (28%) of the 25 eyes after trabeculotomy alone and 7 (25%) of the 28 eyes after the combined procedure, transient IOP elevation was found postoperatively. The incidence of hyphema-related IOP spike was significantly higher in eyes after trabeculotomy alone (16%) than after the combined procedure (0%). After removal of the blood present in the anterior chamber in eyes with hyphema-related IOP spikes, the IOP levels were well controlled., Conclusions: Hyphema-related IOP spike is one of the common complications in eyes after trabeculotomy alone, and the combined procedure decreases the incidence of this complication. It is thought that removal of prolonged massive hyphema is effective as treatment for hyphema-related IOP spike.

It has been reported that isopropyl unoprostone, a prostaglandin-related compound, has potent effects in lowering intraocular pressure and that its hypotensive effect is an increase of uveoscleral outflow. In the present study, we investigated the clinical characteristics of the hypotensive effects of this novel antiglaucoma drug in 115 primary open-angle glaucoma (POAG) eyes. The mean intraocular pressure (+/- standard deviation) before the addition of isopropyl unoprostone to the current regimens was 21.3 +/- 4.4 mmHg. The values at 1 month, 3 months, and 6 months after treatment were, respectively, 20.2 +/- 3.9 mmHg, 19.4 +/- 3.4 mmHg, and 18.4 +/- 2.5 mmHg. In POAG, the outflow pressure difference (delta OP), which is determined as (pretreatment pressure - posttreatment pressure)/(pretreatment pressure - 10) x 100 (%), was reduced by more than 20% in 36 (31%) of 115 eyes, 35 (36%) of 97 eyes, and 33 (53%) of 62 eyes, respectively at 1, 3, and 6 months. We defined the "early success" group as eyes with a significant reduction in delta OP (> or = 20%) at 1-month posttreatment. To identify the prognostic factors related to the significant reduction in intraocular pressure occurring after the administration of this drug, we carried out a statistical analysis by logistic regression analysis. Statistical analysis revealed significant prognostic factors: history of cataract surgery (P = 0.0084) and pretreatment pressure levels (P = 0.0105) at 1-month posttreatment. Also, further statistical analysis showed a significant influence of pretreatment pressure levels (P = 0.0010) at 3 months posttreatment. Our study shows an interindividual difference in the responsiveness of hypotensive effects on POAG eyes and some prognostic factors (history of cataract surgery and pretreatment pressure levels) prior to the use of this drug.

Trabeculectomy is reportedly less effective in aphakic eyes, secondary glaucoma, juvenile patients, and eyes with a history of unsuccessful glaucoma surgery. We evaluated the surgical effects and complications of trabeculectomy with the adjunctive use of mitomycin C, an antiproliferative drug, in a number of refractory cases. Forty patients (50 eyes) with refractory glaucoma were treated with trabeculectomy and the adjunctive use of mitomycin C and were followed postoperatively for at least 3 months. The mean follow-up period was 13.6 +/- 7.5 months (range: 3 to 31 months). In 43 eyes (86%), intraocular pressure was well controlled at < or = 21 mmHg. Complications included corneal epithelial damage (30 eyes), shallow anterior chamber (20 eyes), hyphema (19 eyes), choroidal detachment (18 eyes), leakage of aqueous humor from the conjunctival wound (4 eyes), and endophthalmitis (1 eye). The results of trabeculectomy with intraoperative use of mitomycin C in this series of procedures demonstrates that this can be a useful and effective treatment; however, mitomycin C may cause transient decreased visual acuity due to inhibited wound healing and the resultant overfiltration.