Selective retina therapy (SRT) for macular serous retinal detachment associated with tilted disc syndrome.

PURPOSE: Tilted disc syndrome (TDS) may be associated with a macular serous retinal detachment (MSRD). However, ideal therapy for this complication is still unestablished yet to date. The purpose of this study is to investigate the effect of selective retina therapy (SRT) for MSRD associated with TDS. METHODS: This retrospective study included 11 eyes of 10 patients (1 male and 9 females), who were treated with SRT for MSRD associated with TDS, and observed at least 12 months after treatment. The mean age was 56 years old (range 44-66). An SRT laser (527 nm, 1.7 µs, 100 Hz; Medical Laser Center Lübeck, Germany) was used for treatment. The changes of best-corrected visual acuity (BCVA), central macular thickness (CMT), and central choroidal thickness (CCT) were examined. Subfoveal curve height (SFCH) was calculated at baseline. RESULTS: The mean follow-up period was 24.4 months (range 12-48 months). The mean BCVA (logMAR), CMT, and CCT changed from 0.03 ± 0.10, 324 ± 82 µm, and 194 ± 68 µm preoperatively to 0.07 ± 0.17, 274 ± 94 µm, and 188 ± 65 µm at final follow-up, respectively, with significant difference on CMT (BCVA: p = 0.44, CMT: p < 0.05, CCT: p = 0.21). The MSRD disappeared in 6 eyes (55%) and the average number of SRT irradiations until resolution of MSRD was 2.6 times (range 1-5 times). There was no significant association between SFCH and resolution of MSRD (p = 0.19). CONCLUSIONS: SRT may promote absorption of MSRD and maintenance of BCVA for TDS. Randomized and prospective clinical studies are needed to evaluate the effectiveness of SRT for MSRD associated with TDS.

Predictive factors of outcome of selective retina therapy for diabetic macular edema.

PURPOSE: To investigate the predictive factors of clinical outcome of selective retina therapy (SRT) for diabetic macular edema (DME). METHODS: This retrospective study included 22 eyes of 22 patients (15 males and 7 females), who were treated with SRT for DME at the Department of Ophthalmology of Osaka City University Hospital and observed at least 6 months after the treatment. The mean age was 64 years (range 40-81). Thirteen of the 22 eyes (59%) had a treatment history other than SRT before. SRT laser (527 nm, 1.7 µs, 100 Hz) was used for treatment. Changes in the best-corrected visual acuity (BCVA) (logMAR) and central macular thickness (CMT) in optical coherence tomography were examined at baseline, 3-month follow-up, and 6-month follow-up. Factors associated with the rate of change in CMT at 3 and 6 months after SRT were examined. RESULTS: The mean BCVA (logMAR) was 0.26 ± 0.31, 0.22 ± 0.27 and 0.23 ± 0.29 at baseline, 3 months and 6 months, respectively (p = 0.15 at 3 months, 0.40 at 6 months; compared to baseline). The mean CMT was 502 ± 163, 493 ± 204, and 416 ± 185 µm at baseline, 3 months, and 6 months, respectively (p = 0.69 at 3 months, 0.01 at 6 months; compared to baseline). The multivariate analysis found a significant negative association with previous macular photocoagulation (p = 0.03) at 3 months and a positive association with a history of insulin use (p = 0.02) and previous panretinal photocoagulation (p = 0.03) at 6 months after SRT. CONCLUSION: The CMT was significantly decreased at 6 months after SRT in DME. The history of insulin use and panretinal photocoagulation may positively and the history of macular photocoagulation may negatively affect the outcome of SRT, which must be considered when determining the therapeutic indications for SRT.

Retinal sensitivity after selective retina therapy (SRT) on patients with central serous chorioretinopathy.

PURPOSE: To assess retinal sensitivity after selective retina therapy (SRT) in patients with central serous chorioretinopathy (CSCR). METHODS: Seventeen eyes of 17 patients with CSCR lasting longer than 3 months were treated with SRT (wavelength 527 nm Nd: YLF laser, 50-150 µJ/pulse, spot diameter 200 µm). Measurement of best-corrected visual acuity (BCVA), optical coherence tomography, fluorescence angiography, and microperimetry (MAIA™) were conducted before, and 1 and 3 months after treatment. Microperimetry was performed in the central 10° of the macula, and at the test spots applied near the vascular arcade for energy titration. In addition to the treatment effect, all test irradiation spots were thoroughly analyzed with regard to their sensitivity changes. RESULTS: The mean logMAR BCVA had improved from 0.06 to 0.02 after 1 month (p = 0.11) and to 0.03 after 3 months (p = 0.003). Eleven out of 17 eyes (64.7%) showed complete resolution of subretinal fluid after 3 months. Retinal sensitivity in the central 10° increased after 1 month (median: 25.9 dB) and 3 months (26.6 dB) as compared with that before treatment (23.0 dB) (p < 0.001). Analysis of the test spots revealed a slight decrease in retinal sensitivity after 1 month (ΔdB = -0.5 ± 2.1, p = 0.006), while there was no significant difference from baseline after 3 months (ΔdB = -0.3 ± 2.2, p = 0.09). No correlation was found between laser energy and the change in focal retinal sensitivity. CONCLUSIONS: Results suggest that SRT is a safe and effective treatment for persistent CSCR and does not leave permanent scotoma regardless of irradiation energy in the therapeutic range.

Switching to Intravitreal Brolucizumab after Ranibizumab or Aflibercept Using Treat and Extend Regimen for Neovascular Age-Related Macular Degeneration in Japanese Patients: 1-Year Results and Factors Associated with Treatment Responsiveness.

Objective: To purpose of this study was to retrospectively evaluate the 1-year outcomes and factors associated with the treatment responsiveness of switching to intravitreal brolucizumab (IVBR) for neovascular age-related macular degeneration (nAMD) in Japanese patients refractory to ranibizumab or aflibercept using a treat and extend (TAE) regimen. Methods: A total of 48 eyes of 47 nAMD patients were switched to IVBR, and 36 eyes of 35 patients (27 males and 8 females) underwent 1-year treatment after the switch. Results: The rate of dry macula was significantly higher 12 months after the switch to IVBR (p < 0.001), with a significant decrease in the mean central macular thickness (CMT) and the mean central choroidal thickness (CCT) (p < 0.01 and p < 0.01, respectively). The injection interval was significantly extended from 7.0 ± 1.7 weeks to 10.3 ± 2.5 weeks 12 months after the switch (p < 0.001). In the multivariate analysis, a smaller number of prior anti-VEGF injections (p = 0.025; odds ratio: 0.947; 95% confidence interval: 0.903-0.994) and a pre-switching CCT of less than 250 µm (p = 0.023; odds ratio: 0.099; 95% confidence interval: 0.013-0.731) were associated with the good response group. Conclusions: These results suggest that IVBR may suppress disease activity and prolong the injection interval by switching for AMD patients with an insufficient response to treatment with ranibizumab and aflibercept.

The impact of removing the epiretinal membrane and inner limiting membrane for sustained subretinal fluid by macular neovascularization refractory to anti-VEGF therapy.

Purpose: Anti-vascular endothelial growth factor (VEGF) therapy is the most prevalent intervention for exudative lesions secondary to neovascular age-related macular degeneration (nAMD) and other macular neovascularization (MNV). However, in some cases refractory to the latest anti-VEGF agents is associated with epiretinal membrane (ERM) or vitreomacular traction. We applied a vitrectomy to remove those pathologies which may be effective for reducing the exudation. Observations: In this case report, we present 2 cases with sustained subretinal fluid and macular neovascularization secondary to nAMD or dome-shaped macula that poorly responded to anti-VEGF therapy. In both cases, removing thin ERM or vitreomacular traction with an inner limiting membrane peeling promptly resolved the subretinal fluid and no recurrence was observed thereafter. Conclusions and importance: Vitrectomy could be an effective modality for anti-VEGF drug-resistant MNV cases with vitreomacular traction or ERM even in the anti-VEGF era.

One-Year Outcome of Intravitreal Injection of Ranibizumab Biosimilar for Myopic Choroidal Neovascularization in Japanese Patients.

Objectives: To evaluate the one-year outcomes of intravitreal ranibizumab biosimilar (RBZ-BS) injections for myopic choroidal neovascularization (mCNV) in Japanese patients. Methods: Twenty-one patients (mean age 69.0 years; 4 males, 17 females) with high myopia and mCNV were retrospectively reviewed. Twelve were treatment-naïve, and nine had previous anti-VEGF treatments. Efficacy measures included best-corrected visual acuity (BCVA) and central macular thickness (CMT). Results: The treatment-naïve group showed significant BCVA improvement from 0.55 ± 0.34 at baseline to 0.24 ± 0.28 at 12 months. The previously treated group had no significant BCVA changes. CMT significantly decreased in both groups: from 295.3 ± 105.2 µm to 207.3 ± 63.0 µm in the treatment-naïve group, and from 196.1 ± 62.0 µm to 147.2 ± 50.1 µm in the previously treated group. Dry macula rates were high: 83% at 3 months and 83% at 12 months in the treatment-naïve group, and 67% at 3 months and 89% at 12 months in the previously treated group. No adverse events were reported. Conclusions: These findings indicate that RBZ-BS is an effective and safe treatment for mCNV, particularly in treatment-naïve patients. The use of RBZ-BS offers a cost-effective alternative to original ranibizumab, reducing financial burdens while maintaining high therapeutic efficacy. Further studies with larger sample sizes and longer follow-up periods are needed to confirm these results and evaluate long-term outcomes and cost-effectiveness.

Practical treatment options for persistent central serous chorioretinopathy and early visual and anatomical outcomes.

PURPOSE: Persistent central serous chorioretinopathy (pCSC) may be treated by laser photocoagulation (PC), selective retina therapy (SRT), or photodynamic therapy (PDT). We conducted retrospective analyses regarding the choice of therapy for pCSC in the best clinical practice and the outcomes of these modalities. STUDY DESIGN: A retrospective interventional study. METHODS: The records of 71 eyes of 68 treatment naïve pCSC cases who underwent PC, SRT, or PDT were reviewed. First, the baseline clinical parameters were evaluated to find significant factors associated with the choice of treatment option. Second, the 3 months' visual and anatomical outcomes of each modality were assessed. RESULTS: The PC, SRT, and PDT groups included 7, 22, and 42 eyes, respectively. The leakage pattern in fluorescein angiography (FA) was significantly associated with the choice of treatment (p<0.005). The dry macula ratio at 3 months post-treatment was 29%, 59%, and 81% in the PC, SRT, and PDT groups, respectively, which significantly differed among the groups (p<0.01). The best-corrected visual acuities tended to be improved after the treatments in all groups. Central choroidal thickness (CCT) was significantly decreased in all groups (p<0.05, p<0.01, and p<0.00001, in PC, SRT, and PDT groups, respectively). Logistic regression analysis for dry macula revealed that SRT (p<0.05), PDT (p<0.05), and the changes in CCT (p<0.01)were the significant association factors. CONCLUSION: The leakage pattern in FA was associated with the choice of treatment option for pCSC. PDT achieved a significantly higher dry macula ratio than PC, 3 months after the treatment.

Comparative Treatment Study on Macular Edema Secondary to Branch Retinal Vein Occlusion by Intravitreal Ranibizumab with and without Selective Retina Therapy.

The purpose of this study was to compare the safety and efficacy of selective retina therapy (SRT) combined with the intravitreal injection of ranibizumab (IVR) in patients with macular edema (ME) secondary to branch retinal vein occlusion (BRVO). This trial was a 12-month single-center, randomized, single-masked prospective study. Eligible patients were randomized (1:1) to IVR and SRT (IVR + SRT group), or IVR and sham SRT (IVR + sham group). After the initial IVR, all participants received ME resolution criteria-driven pro re nata treatment. SRT or sham SRT was always applied one day after IVR. The primary outcome measure of this study was the mean change in central macular thickness (CMT) from baseline, and the secondary outcome measures were the mean change in visual acuity from baseline and the number of IVR treatments at a 52-week follow-up. Thirteen patients were in the IVR + SRT group, and 11 were in the IVR + sham group. Compared to the baseline, mean CMT and BCVA improved significantly after 52 weeks in both groups, with no significant difference between the two groups. The mean number of IVR was 2.85 ± 1.52 in the IVR + SRT group and 4.73 ± 2.33 in the IVR + sham group at the 52-week follow-up, with a significant difference between the two groups (p < 0.05). IVR combined with SRT may significantly decrease the number of IVR treatments while maintaining the visual and anatomical improvement effect of IVR monotherapy.

Early anatomical changes and association with photodynamic therapy induced acute exudative maculopathy in patients with macular diseases.

The purpose of this study was to investigate the occurrence rate and predictors of photodynamic therapy (PDT) induced acute exudative maculopathy (PAEM). This retrospective study included 39 eyes of 39 patients (32 males and 7 females), who were treated with initial PDT. PAEM was defined as an increase in central retinal thickness (CRT) of 15% or more measured by OCT on day 3 after PDT compared with baseline. Sixteen of 39 eyes (41%) were classified in the PAEM+ group. CRT and central choroidal thickness (CCT) were significantly increased at 3 days in the PAEM+ group and significantly decreased at 1 month after PDT in the PAEM- group. In a multiple comparison, neovascular age-related macular degeneration (nAMD) had a significantly higher incidence of PAEM compared to polypoidal choroidal vasculopathy (PCV) and central serous chorioretinopathy (CSC). The incidence of PAEM was lower in PCV and CSC, and higher in nAMD. BCVA at 1 month was significantly worse in the PAEM group, which may be related to visual prognosis after PDT. Since both CRT and CCT decrease at 1 month, the detection of PAEM needs to be assessed a few days after PDT.

Factors affecting resolution of subretinal fluid after selective retina therapy for central serous chorioretinopathy.

The purpose of this study was to investigate the factors of clinical outcome of selective retina therapy (SRT) for central serous chorioretinopathy (CSC). This retrospective study included 77 eyes of 77 patients, who were treated with SRT for CSC and observed at least 6 months after the treatment. SRT laser (527 nm, 1.7 µs, 100 Hz) was used for treatment. The mean best-corrected visual acuity (logMAR), central macular thickness (CMT) and central choroidal thickness were changed from baseline to at 6-months follow-up with significant difference. The multivariate analyses found that the rate of change (reduction) in CMT was associated with focal leakage type on fluorescein angiography (FA) (p = 0.03, coefficient 15.26, 95% confidence interval 1.72-28.79) and larger baseline CMT (p < 0.01, coefficient - 0.13, 95% confidence interval - 0.13 to - 0.05). Complete resolution of subretinal fluid was associated with nonsmoking history (p = 0.03, odds ratio 0.276, 95% confidence interval 0.086-0.887) and focal leakage type on FA (p < 0.01, odds ratio 0.136, 95% confidence interval 0.042-0.437). These results may be useful for predicting the therapeutic effectiveness of SRT.

Selective retina therapy for subretinal fluid associated with choroidal nevus.

PURPOSE: To report a case of a patient with subretinal fluid (SRF) associated with choroidal nevus (CN), who was treated with selective retina therapy (SRT) and ultimately achieved resolution of the SRF. OBSERVATIONS: A 41-year-old man with SRF associated with CN in his right eye (RE) underwent ophthalmologic evaluation, including optic coherence tomography, fluorescein angiography (FA) and indocyanine green angiography. The best corrected visual acuity (BCVA) converted to the logarithm of the minimum angle of resolution (logMAR) was 0.00 in the RE. SRT (532 nm, 1.7 µs pulse duration, 30 pulses in 100Hz; Medical Laser Center Lübeck) was performed with the laser spots equally distributed across the FA leakage area. Until 20 months SRT was repeated several times because the SRF decreased every time in response to SRT, but was not completely resolved and sometimes increased with time. After performing 6 times of SRT session, leakage on FA stopped at 21 months follow-up and SRF was resolved at 31 months. At 60 months after the first SRT, there were no signs of malignant transformation, no SRF, and the BCVA in the RE was 0.22. CONCLUSIONS AND IMPORTANCE: SRT seems to be a useful treatment and proper clinical studies are necessary to establish the best treatment protocol for SRF associated with CN.

One-Year Results of a Treat-and-Extend Regimen of Intravitreal Aflibercept for Polypoidal Choroidal Vasculopathy.

INTRODUCTION: To evaluate 1-year outcomes of intravitreal aflibercept (IVA) using a treat-and-extend (TAE) regimen for polypoidal choroidal vasculopathy (PCV) and identify the factors for patients whose treatment intervals could be extended. METHODS: Fifty-one eyes of treatment-naïve PCV patients treated with IVA using a TAE regimen for at least 1 year were examined retrospectively. All patients received at least three IVA injections every 5 weeks, and the intervals were then extended by 2-week adjustments up to 13 weeks. When retinal exudation recurred, the patient was treated with the same regimen, but with a shortened interval of 5 weeks. The main outcome measures were changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) as well as the treatment interval at 1 year. RESULTS: The mean logarithm of the minimum angle of resolution BCVA improved from 0.24 ± 0.32 at baseline to 0.18 ± 0.31 at 12 months (p = 0.048). The mean CRT decreased from 350.3 ± 147.7 µm at baseline to 215.3 ± 75.0 µm at 4 months (p < 0.001), after which it was maintained at this level. At 12 months, the administration interval was 5 weeks in eight eyes (15.7%), 7 weeks in six eyes (11.8%), 9 weeks in two eyes (3.9%), 11 weeks in four eyes (7.8%), and 13 weeks in 31 eyes (60.8%). Female sex, a thinner CRT at 6 months, and absence of polypoidal lesions at 12 months were significant factors related to patients whose treatment intervals could be extended without recurrence to 13 weeks. CONCLUSION: IVA using a TAE regimen improved visual and anatomical outcomes in eyes with PCV at 1 year using a protocol to adjust the injection intervals specifically for each patient so as to obtain no retinal exudation.

The involvement of the rho-kinase pathway and its regulation in cytokine-induced collagen gel contraction by hyalocytes.

PURPOSE: To investigate the involvement of the Rho-kinase pathway in collagen gel contraction by hyalocytes. METHODS: An in vitro type I collagen gel contraction assay using cultured bovine hyalocytes was performed to evaluate the effect of PDGF-BB and TGF-beta2. The effect of both cytokines on the phosphorylation of myosin light chain (MLC) was analyzed by Western blot analysis. To confirm the involvement of the Rho-kinase pathway in the collagen gel contraction, the effects of Y27632, a specific Rho-kinase inhibitor were examined. The effect of hydroxyfasudil, another potent Rho-kinase inhibitor, was also evaluated. The expression of alpha-smooth muscle actin (alphaSMA) was analyzed by Western blot analysis to examine the myofibroblast-like transdifferentiation of the hyalocytes. RESULTS: Maximum collagen gel contraction was observed within 24 hours after treatment with PDGF-BB and much stronger contraction with TGF-beta2, whose effect was time dependent, at least up to 5 days. Although transient and maximum MLC phosphorylation by PDGF-BB was observed at approximately 4 hours after stimulation (180.8%, P <0.01), TGF-beta2-elicited MLC phosphorylation occurred in a time-dependent manner at least up to 24 hours (220.0%, P <0.01) and was maintained up to 5 days. Y27632 demonstrated significant inhibition of collagen gel contraction induced by both cytokines. Hydroxyfasudil dose-dependently (0.03-20.00 microM) prohibited the phosphorylation of MLC, and inhibited collagen gel contraction at a concentration corresponding to that which inhibited MLC phosphorylation. TGF-beta2, but not PDGF-BB, also caused myofibroblast-like transdifferentiation with alphaSMA overexpression, which was downregulated by hydroxyfasudil in part (P <0.01). CONCLUSIONS: The hyalocytes have a contractile property in the presence of PDGF-BB and TGF-beta2. Whereas PDGF-BB initiates collagen gel contraction by transient activation of the Rho-kinase pathway, sustained activation of the Rho-kinase pathway and myofibroblast-like transdifferentiation appears to be involved in the TGF-beta2-dependent contractile properties of hyalocytes.

Functional properties of hyalocytes under PDGF-rich conditions.

PURPOSE: To investigate the functional properties and intracellular signaling of hyalocytes under platelet-derived growth factor (PDGF)-rich conditions. METHODS: The hyalocytes were isolated from bovine eyes and identified by immunocytochemistry and electron microscope. The expression of PDGF receptor alpha/beta and its phosphorylation in response to PDGF-BB was analyzed by Western blot analysis. PDGF-BB-induced proliferation and migration were evaluated by thymidine uptake and Boyden's chemotaxis assay. The expression of the urokinase-type plasminogen activator (uPA) gene and the fibrinolytic activity were assessed by Northern blotting and fibrin zymography. An in vitro type I collagen gel contraction assay was performed to determine the effect of PDGF-BB on cellular contraction. RESULTS: The hyalocytes were immunocytochemically positive for S-100 and negative for glial fibrillary acidic protein (GFAP) and cytokeratin, as previously described. The electron microscope demonstrated that hyalocytes possess lysosome-like granules, mitochondria, and micropinocytotic vesicles in their cytoplasm. The hyalocytes expressed PDGF receptor alpha and beta, both of which were immediately phosphorylated in response to PDGF-BB. PDGF-BB also activated p85 PI3-kinase, p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase. PDGF-BB induced thymidine uptake and migration in a concentration-dependent (0-10 ng/mL) manner. Inhibitors of the respective kinases prohibited PDGF-BB-dependent thymidine uptake and migration with the exception of the p44/p42 MAP kinase inhibitor, which displayed no inhibitory effects on migration. PDGF-BB increased uPA gene expression and fibrinolytic activity. Collagen gel contraction observed under PDGF-BB-rich conditions was not prohibited by the respective inhibitors investigated. CONCLUSIONS: The hyalocytes demonstrated macrophage-like characteristics and may have both physiologic and pathologic roles, such as the maintenance of vitreous transparency through fibrinolytic activity and the pathogenesis of proliferative-vitreoretinal diseases through cellular proliferation and vitreous hyper-contraction.

[Correlation of the presence of meibomian gland dysfunction with the incidence of superficial punctate keratopathy after penetrating keratoplasty].

PURPOSE: To examine the correlation of the presence of meibomian gland dysfunction(MGD) with the incidence of superficial punctate keratopathy (SPK) after penetrating keratoplasty. SUBJECTS & METHODS: We studied 151 eyes of 141 patients that underwent penetrating keratoplasty. SPK and the presence of MGD were evaluated by slit-lamp examination. Tear function was evaluated by Schirmer test. RESULTS: Among 151 eyes investigated, 78 eyes had neither MGD nor hypolacrimation. The number of eyes with MGD only, with hypolacrimation only, or with both MGD and hypolacrimation was 34, 23, and 16. The presence of SPK after penetrating keratoplasty was correlated with the presence of MGD 1 month or 6 months post-surgery, but no correlation was observed with the presence of hypolacrimation. There was no interaction between the presence of MGD and hypolacrimation and the incidence of SPK. CONCLUSION: This study suggested that the active treatment of MGD is important in the post-surgery management of SPK.

Critical role of the Rho-kinase pathway in TGF-beta2-dependent collagen gel contraction by retinal pigment epithelial cells.

Retinal pigment epithelial cells (RPEs) are thought to be one of the main components of fibrous membrane observed in eyes with proliferative vitreo-retinopathy. We investigated the signalling mechanisms of TGF-beta2-dependent collagen gel contraction by RPEs. An in vitro type I collagen gel contraction assay was performed to evaluate the effect of TGF-beta2 on gel contraction. The expression of alpha-smooth muscle actin (alpha-SMA) and the phosphorylation state of myosin light chain (MLC) were analyzed by Western blotting. The involvement of protein kinases such as p44/42 mitogen-activated protein kinase (MAPK), protein kinase C (PKC), p38 MAPK and phosphatidylinositol-3 kinase was investigated. The contribution of Rho-kinase and/or MLC-kinase was also evaluated using respective kinase inhibitors (Y27632, hydroxyfasudil and ML7). Additionally, RPEs were immunostained to examine whether the expression of alpha-SMA detected in our western blotting correlated to the stress fiber formation within the cells. TGF-beta2 caused time (0-5 days)-and dose (0 10 ng ml(-1))-dependent gel contraction associated with overexpression of alpha-SMA and phosphorylation of MLC (p < 0.01, respectively). PKC inhibitor (GF109203X, 5 microM) and p38 MAPK inhibitor (SB203580, 10 microM) significantly attenuated TGF-beta2-elicited gel contraction via partial downregulation of both alpha-SMA expression and MLC phosphorylation (p < 0.01, respectively). The gel contraction was prominently inhibited in the presence of Y27632 (10 microM) or hydroxyfasudil (10 microM) with strong suppression of MLC phosphorylation but had no significant effect on alpha-SMA expression. Treatment with ML7, in contrast, resulted in a marginal inhibition of MLC phosphorylation and gel contraction. Finally, pretreatment of the cells with Y27632 or hydroxyfasudil prevented the formation of stress fiber within the cells. These results indicate that TGF-beta2-dependent myofibroblastic transdifferentiation and MLC phosphorylation by RPEs involve both PKC and p38 MAPK pathways at least in part. Myofibroblastic transdifferentiation of RPEs appears to be independent of the Rho-kinase pathway, and the presence of alpha-SMA does not necessarily reflect the contractile potential of a cell. While Rho-kinase inhibitors are incapable of preventing myofibroblastic transdifferentiation itself, this pathway could be one of the critical targets of cell-mediated contraction of the tissue containing fibrillar collagens by transdifferentiated RPEs.