Factors correlated with visual outcomes at two and four years after vitreous surgery for proliferative diabetic retinopathy.

Proliferative diabetic retinopathy (PDR) is the most severe case of diabetic retinopathy that can cause visual impairment. This study aimed to reveal the factors correlated with better postoperative visual acuity after a long follow-up in patients who underwent vitrectomy for PDR. We retrospectively analyzed the data set including systemic findings, ocular findings, and surgical factors from registered patients who could be completely followed up for 2 or 4 years after vitrectomy. We ultimately enrolled 128 eyes from 100 patients who underwent vitrectomy for PDR between January 2008 and September 2012 and were followed up for >2 years. Among them, 91 eyes from 70 patients could be followed up for 4 years. Factors related to the postoperative visual acuity of ≥20/40 and ≥20/30 after 2 and 4 years were investigated by logistic regression analysis. Better postoperative visual acuity correlated with the following factors: no rubeosis iridis ([≥20/40 at 2 years; odds ratio {OR}, 0.068; 95% confidence interval {CI}, 0.012-0.39; P = 0.003], [≥20/30 at 2 years; OR, 0.07; 95% CI, 0.01-0.40; P = 0.03], [≥20/30 at 4 years; OR, 0.078; 95% CI, 0.006-0.96; P = 0.04]), no fibrovascular membrane [(≥20/40 at 2 years; OR, 0.22; 95% CI, 0.061-0.81; P = 0.02), (≥20/40 at 4 years; OR, 0.26; 95% CI, 0.07-0.94; P = 0.04), (≥20/30 at 4 years; OR, 0.14; 95% CI, 0.04-0.52; P = 0.004)], existing vitreous hemorrhage (≥20/30 at 2 years; OR, 9.55; 95% CI, 1.03-95.27; P = 0.04), and no reoperation ([≥20/40 at 4 years; OR, 0.15; 95% CI, 0.03-0.78; P = 0.02], [≥20/30 at 4 years; OR, 0.06; 95% CI, 0.07-0.54; P = 0.01]). Treatment provision before disease severity and treatment without complications were associated with good postoperative visual acuity.

Long-term outcomes of 3 surgical adjuvants used for internal limiting membrane peeling in idiopathic macular hole surgery.

PURPOSE: Indocyanine green (ICG), an adjuvant used for peeling of the internal limiting membrane (ILM) during vitreous surgery for idiopathic macular hole (MH), has been reported to be toxic, possibly affecting postoperative visual acuity. We compared the long-term outcomes (within 2 years) of brilliant blue G (BBG), ICG, and triamcinolone acetonide (TA). PATIENTS AND METHODS: This study involved 97 eyes of 94 patients who underwent vitreous surgery for MH at the Yamagata University Hospital between June 2002 and November 2010. The surgical adjuvants used were BBG for 15 eyes, ICG for 61 eyes, and TA for 21 eyes. We compared the postoperative visual acuities, initial closure rates, final closure rates, and complications of the 3 groups. RESULTS: In all 3 groups, the visual acuity significantly improved after surgery. The magnitude of the improvement at 2 years after surgery was significantly better in the BBG group than in the ICG group (Mann-Whitney test, P = 0.020). The postoperative visual acuity did not significantly differ between the BBG and TA groups (P = 0.627) or between the ICG and TA groups (P =0 .137). Thus, the surgery using BBG resulted in a significantly better outcome in visual acuity than did the surgery using ICG. The 3 groups did not differ in initial or final closure rates or in incidence of complications. CONCLUSION: Analysis of the long-term outcomes of vitreous surgeries provided evidence that BBG is a useful adjuvant for ILM peeling.

Three-dimensional imaging of the inner limiting membrane folding on the vitreomacular interface in diabetic macular edema.

PURPOSE: To report the findings of fine folds on the retina obtained by spectral-domain optical coherence tomography (OCT). METHODS: A retrospective non-comparative case series; 26 eyes of diabetic macular edema (DME) patients who underwent vitrectomy were observed using three-dimensional (3D) images of OCT preoperatively and postoperatively. The specimens were investigated immunohistochemically. RESULTS: Using only tomography, non-tractional vitreoretinal interfaces were observed in 15 eyes and tractional vitreoretinal interfaces in the other 11 eyes. Using 3D imaging, we observed fine folds in 11 eyes among 15 cases showing non-tractional interfaces. Based on these findings, the state of the vitreoretinal interface was classified into 3 patterns. Group 1, both tomography and 3D imaging showed smooth retinal surfaces. Group 2, tomography showed a smooth retinal surface, but 3D imaging showed fine folds on the retina. Group 3, both tomography and 3D imaging showed a tractional vitreoretinal interface with an obvious epiretinal membrane and/or taut posterior vitreous cortex. The fine folds in group 2 disappeared and macular edema improved after inner limiting membrane (ILM) peeling, and the CRT of groups 2 and 3 reduced significantly. The fine folds were confirmed to involve the ILM because type IV collagen expression was detected in the surgically obtained specimens. CONCLUSION: We observed tangential fine folds of the ILM. These were detected by using only 3D imaging, and might be useful for investigating the optimal indication of vitrectomy for DME.

Prevalence and risk factors for diabetic maculopathy, and its relationship to diabetic retinopathy in elderly Japanese patients with type 2 diabetes mellitus.

AIMS: To determine the prevalence of diabetic retinopathy and diabetic maculopathy in Japanese patients older than 65 years-of-age with type 2 diabetes mellitus. In addition, to determine the relationship between the severity of retinopathy and maculopathy, and the risk factors for these conditions in Japanese patients with the same characteristics. METHODS: This was a cross-sectional study carried out at the enrolment of patients who participated in a randomized controlled trial. A total of 960 eyes of 960 Japanese patients with type 2 diabetes who were ≥ 65 years-of-age were analyzed. RESULTS: Our data showed that there was a correlation between the severity of retinopathy and the severity of maculopathy. The risk factors for the severity of retinopathy were different from the risk factors for the severity of maculopathy. The age, duration of diabetes, systemic pulse pressure, fasting insulin, insulin treatment of diabetes, high-density lipoprotein cholesterol, microalbumin-to-creatinine ratio and history of cerebrovascular disease all contributed significantly to the severity of retinopathy. The duration of diabetes, insulin treatment and microalbumin-to-creatinine ratio were correlated with the severity of maculopathy. CONCLUSIONS: The risk factors related to diabetic retinopathy and maculopathy in Japanese patients with type 2 diabetes mellitus aged ≥ 65 years were different from that in other countries. Our data also showed that the certain risk factors for retinopathy differ from those associated with maculopathy.

Treatment of diffuse diabetic macular oedema using steroid eye drops.

PURPOSE: To evaluate the efficacy of treatment of diffuse diabetic macular oedema (DME) with difluprednate ophthalmic emulsion 0.05% (Durezol™) in eyes before vitrectomy. METHODS: This study enrolled patients with diffuse DME for whom more than 3 months had passed since prior treatment. Nineteen eyes in 15 subjects were treated with difluprednate ophthalmic emulsion 0.05% four times daily for the first month and then twice daily for 2 months (treatment group). As a control group, 22 eyes in 11 subjects with DME were selected from subjects who underwent the steroid responder test. RESULTS: In the treatment group, the mean visual acuity (VA) (±SD) was 0.38 ± 0.25 logMAR and mean retinal thickness was 461.1 ± 109.9 µm at baseline. After 1 month of treatment, the mean VA had improved to 0.29 ± 0.25 (Wilcoxon rank-sum test, p = 0.30), while mean retinal thickness had decreased to 372.1 ± 70.0 µm (p = 0.006). The rate of effective improvement in retinal thickness was 42% and that of VA was 26%. In the control group, changes in neither VA nor retinal thickness were significant. CONCLUSIONS: Eye drop therapy using difluprednate ophthalmic emulsion 0.05% is a useful and effective treatment modality without surgical intervention or severe side-effects.

Difluprednate ophthalmic emulsion 0.05% as adjunctive treatment to panretinal photocoagulation for proliferative diabetic retinopathy with clinically significant macular edema.

PURPOSE: The purpose of this study was to evaluate the efficacy of topical difluprednate ophthalmic emulsion in controlling progressive diabetic macular edema after panretinal photocoagulation. METHODS: This was a case report of two patients with proliferative diabetic retinopathy combined with diabetic macular edema who underwent panretinal photocoagulation combined with use of a topical difluprednate ophthalmic emulsion. RESULTS: In the Case 1, retinal thickness was decreased 29% 1 month after the start of difluprednate treatment and best-corrected visual acuity was improved 20/40 to 20/25. In Case 2, retinal thickness was decreased 43% after 1 month, and best-corrected visual acuity was improved 20/100 to 20/60 after 3 months. During the follow-up period, elevation of intraocular pressure, ocular infection, and progression of cataract were not detected, though superficial punctuate keratitis was observed in one case. CONCLUSION: Topical difluprednate ophthalmic emulsion was one of the possible choices to treat progressive diabetic macular edema after panretinal photocoagulation. It is mandatory to evaluate the effects and safety in further studies including many cases.

Hyaluronan production and hyaluronan synthase expression in three human conjunctiva-derived cell strains.

PURPOSE: The conjunctiva maintains the health of the ocular surface by protecting the eye from pathogen invasion, injury, and dryness. In this study, we investigated the regulation of hyaluronan (HA) synthesis by cytokines in conjunctiva-derived cells. METHODS: Cultured primary cells derived from human conjunctivas that had been removed as surgical specimens were transfected with an immortalizing gene (human papilloma virus 16 E6/E7). To compare the biological features of the primary and immortalized cells, we assessed their morphological features and gene expression patterns. We also examined the effects of inflammatory cytokines on hyaluronan synthase (HAS) expression and HA production. RESULTS: Three conjunctiva-derived cell strains were established and could be passaged up to 15 times. All strains expressed ß2MG and KRT13 transcripts, highly expressed in conjunctival epithelial cells. HA production and expression of the three HAS isoforms were detected in the cell strains; however, cytokine treatment had no significant effect on HA production or HAS isoform expression. CONCLUSIONS: We succeeded in deriving three human cell strains from conjunctival tissue. In the conjunctiva-derived cell strains, HA production and HAS mRNA expression were stable and were not changed by either TGF-ß or PDGF-BB.

Cloning and characterization of human vitreous tissue-derived cells.

PURPOSE: Previously, we established a porcine vitreous tissue-derived hyalocyte cell line (PH5) and investigated the regulation of hyaluronan synthesis in these cells by cytokines. The objective of the current study was to establish human vitreous tissue-derived cells and to compare their characteristics with those of PH5 cells. METHODS: Human vitreous specimens from two patients were cultured in the presence of 10% foetal bovine serum and immortalized by infection with human papilloma virus 16 genes E6 and E7. We used reverse transcription polymerase chain reaction (RT-PCR) to analyse and compare the expression profiles for several genes in the human vitreous tissue-derived cells and PH5 cells. To investigate the regulation of hyaluronan production in response to cytokine stimulation, the expression of hyaluronan synthase isoforms was examined using RT-PCR, and hyaluronan production was measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: Two types of cells, HV64 and HV65, were derived from human vitreous tissue. The HV64 and HV65 cell-doubling times were 58 r and 76 hr, respectively. The cells expressed messenger RNA (mRNAs) encoding collagen type I α1 (COL1A1), collagen type II α1 (COL2A1), CD11b, CD14, CD68, CD204 and CD206 but did not express mRNA for glial fibrillary acidic protein (GFAP). Cytokine stimulation did not induce the expression of hyaluronan synthase mRNA or the production of hyaluronan. In contrast, mRNAs for GFAP and hyaluronan synthase-2 were expressed in the porcine PH5 cells, and treatment with transforming growth factor-ß1 and/or platelet-derived growth factor-BB induced the production of hyaluronan in PH5 cells. CONCLUSION: The new human vitreous tissue-derived cells have macrophage-like characteristics and are different from our previously developed porcine hyalocyte cells. These human vitreous tissue-derived cells might be useful for studies of human intraocular diseases.

Cotylenin A inhibits cell proliferation and induces apoptosis and PAX6 mRNA transcripts in retinoblastoma cell lines.

PURPOSE: Retinoblastoma, a childhood cancer of the retina, is caused by inactivation of the tumor suppressor gene retinoblastoma (RB). Cotylenin A (CN-A), a novel fusicoccane-diterpene glycoside, accelerates the differentiation of several types of myeloid cell lines and is a candidate for a new type of anticancer therapeutic agent with this effect. However, whether CN-A has the same effect on retinoblastoma cells is unknown. We studied the response of two retinoblastoma cell lines, Y-79 and WERI-Rb-1, to CN-A. METHODS: We studied the response of two retinoblastoma cell lines to CN-A with respect to cell growth, apoptosis, morphology, mRNA, protein expression analysis of specific genes (N-myc, cyclin-dependent kinase inhibitor 1A [P21], paired box gene 6 [PAX6], and rhodopsin [RHO]), and activity of three PAX6 promoters (P0, P1, and Palpha). RESULTS: CN-A inhibited cell proliferation and induced apoptosis via caspase activity in the two retinoblastoma cell lines. In addition, CN-A induced mRNA expression of P21, PAX6, and RHO and protein expression of P21. In Y-79 cells, PAX6 P1 promoter was activated by CN-A. In WERI-Rb-1 cells, PAX6 P0, P1, and Palpha promoter were activated by CN-A. CN-A decreased mRNA and protein expression of N-myc in two retinoblastoma cell lines. CONCLUSIONS: The responses of retinoblastoma cells to CN-A include inhibition of cell growth, induction of apoptosis, and the potential to change neuroblastoma characteristics of retinoblastoma cells.

Association of PDGF-BB-induced thrombomodulin with the regulation of inflammation in the corneal and scleral stroma.

PURPOSE: The responses of corneal and scleral stromal cells to platelet-derived growth factor (PDGF)-BB were assessed and inflammatory reactions in the cornea and sclera were investigated. METHODS: Primary cultures of cells obtained from human subjects and strains derived from human corneal or scleral stromal cells (Cs3 and Sc1, respectively) were used. Changes in gene expression after 24 hours of exposure to 10 ng/mL PDGF-BB were analyzed with an Sc1 DNA microarray. The upregulation of several genes in Cs3 and Sc1 was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. The expression of bioactive factors was detected immunohistochemically in nine different clinical specimens. RESULTS: DNA microarray analysis revealed that the gene encoding thrombomodulin (TM) was induced in Sc1 by PDGF-BB. RT-PCR confirmed that TM expression at the mRNA level was increased in both corneal and scleral stromal cells. At the protein level, TM expression was increased in scleral stromal cells, but not in corneal cells, and TM was detected in both the membrane and cytoplasmic compartments. TM was detected immunohistochemically in inflamed scleral and several corneal specimens. After TM stimulation, interleukin (IL)-18 transcription was increased in Sc1. CONCLUSIONS: PDGF-BB induced TM mRNA expression in scleral and corneal stromal cells, but Western blot analysis revealed the increase in TM expression only in the scleral cells. TM induced IL-18 in scleral stromal cells. A cascade involving these biologically active factors may regulate scleral and corneal inflammation. The results also reveal differences in the biological response of scleral and corneal stromal cells.

Three-Dimensional Features of Polypoidal Choroidal Vasculopathy Observed by Spectral-Domain OCT.

Five eyes of five patients with polypoidal choroidal vasculopathy (PCV) without acute hemorrhagic changes or subretinal proliferative tissue to observe the three-dimensional structures and to demonstrate the nature of these images and their interpretation. The abnormal networks surrounding polypoidal lesions were considered to be abnormal pathological blood vessels. The segmentation analysis of spectral-domain optical coherence tomography (OCT) has revealed the three-dimensional features of polypoidal lesions and surrounding abnormal blood vessel networks beneath retinal pigment epithelium. The changes of pathological findings of PCV were also detected, including the enlargement of hemorrhagic pigment epithelium detachment (PED). The segmentation analysis is useful to observe PCV lesions from the bird's eye view.

The in vitro response of human retinal endothelial cells to cytokines and other chemically active agents is altered by coculture with vitreous-derived hyalocytes.

BACKGROUND: Ocular angiogenesis is regulated by polypeptides including cytokines, which are known to affect vascular endothelial cells. We have reported that hyalocytes interact with vascular endothelial cells, and some cytokines affect these interactions. AIMS: To determine the effect of various chemically active agents on the viability of endothelial cells alone and cocultured with hyalocytes. METHODS: The viability of human retinal endothelial cells (HRECs) was determined after exposure to IL-1alpha, IL-1beta, IL-6, TNFalpha and VEGF using the MTT assay. These results were compared to the viability when the HRECs were cocultured with porcine hyalocytes that had been exposed to different types of cytokines. The effects of bevacizumab, fenofibrate and dexamethasone on the viability of HRECs in coculture with hyalocytes were also assessed. RESULTS: Ten micrograms/millilitre of bevacizumab decreased the percentage of living HRECs stimulated by VEGF without hyalocytes, but with the hyalocytes, 100 microg/ml of bevacizumab was required to decrease the percentage of viable HRECs stimulated by VEGF. Fenofibrate, at 5 microg/ml, decreased the viability of HRECs stimulated by IL-1beta and VEGF without hyalocytes but could not decrease the viability of HRECs cocultured with hyalocytes. Dexamethasone, at 50 microg/ml, decreased the viability of HRECs stimulated by IL-1alpha, IL-1beta, IL-6 and VEGF without hyalocytes but could not decrease the viability of HRECs cocultured. CONCLUSIONS: Coculturing HRECs with vitreous-derived hyalocytes depressed the effects of cytokines, bevacizumab, fenofibrate and dexamethasone. This suggests that the vitreal hyalocytes may play a role in pathogenic endothelial cell proliferation in vivo. Future studies to better understand this pathobiology should utilize coculture systems of HRECs and vitreal hyalocytes.

Steroid eye drop treatment (difluprednate ophthalmic emulsion) is effective in reducing refractory diabetic macular edema.

PURPOSE: To evaluate the efficacy of treatment of refractory diabetic macular edema (DME) after vitrectomy with difluprednate ophthalmic emulsion 0.05% (Durezol(TM)), and to compare this treatment with sub-Tenon's injection of triamcinolone (STTA). METHODS: This study enrolled patients with refractory diabetic macular edema that persisted despite pars plana vitrectomy in our clinic. In all subjects, more than 3 months had passed since prior treatment. Eleven eyes in ten subjects were treated with STTA (STTA group), and 11 eyes in seven subjects were treated with difluprednate ophthalmic emulsion 0.05% (Durezol(TM), Sirion Therapeutics Inc., USA) 4 times daily for the first month and then twice daily for 2 months (eye drop group). RESULTS: In the eye drop group, mean VA (+/- SD) was 0.67 +/- 0.35 logMAR and mean retinal thickness was 500.6 +/- 207.7 mum at baseline. After 3 months of treatment, mean VA was 0.67 +/- 0.29 and mean retinal thickness had decreased to 341.2 +/- 194.8 mum. The mean minimum value of RT during the treatment period was 300.6 +/- 123.2 mum, and significantly lower than that at baseline (Mann-Whitney U test: P = 0.003). In the STTA group, mean VA (+/- SD) was 0.67 +/- 0.35 logMAR, and mean retinal thickness was 543.3 +/- 132.6 mum at baseline. After 3 months of treatment, mean VA was 0.49 +/- 0.67, and mean retinal thickness had decreased to 378.6 +/- 135 mum. The mean minimum value of RT during the treatment period was 349.9 +/- 113.8 mum, and significantly lower than at baseline (Mann-Whitney U test: P = 0.003). The rate of effective improvement in RT did not differ between the eye drop group (73%) and STTA group (84%) (Fisher's exact test: P = 1). CONCLUSIONS: Comparable improvements of retinal thickness were observed in the STTA and eye drop groups. Instillation of difluprednate ophthalmic emulsion 0.05% is a safe and effective treatment that does not require surgical intervention and does not produce severe side-effects.

Cup-shaped choroidal excavation detected by optical coherence tomography: a case report.

PURPOSE: The purpose of this study was to report a case with a cup-shaped choroidal excavation in the fovea. This condition was detected only by optical coherence tomography (OCT) and seems to be rare. METHOD: This was an observational case report. RESULT: A 29-year-old man had a central scotoma in his right eye. Color photography showed a reddish lesion in the fovea of the right eye, which was shown as a window defect on fluorescein angiography. Tomography with time-domain OCT showed a retinal pigment epithelial and choroidal excavation corresponding to the reddish macular lesion in the right eye. By using spectral-domain OCT, the inner segment and outer segment junctions of photoreceptors line thickening was detected by tomography, and the retinal pigment epithelium line was observed in the area of choroidal excavation by segmentation analysis. CONCLUSION: The reddish lesion on ophthalmoscope corresponded to the excavation lesion, detected in the fovea only by OCT; this indicates a new clinical availability of OCT in clinical diagnosis.

Trichostatin A-induced TGF-beta type II receptor expression in retinoblastoma cell lines.

PURPOSE: Retinoblastoma, an intraocular malignant tumor of childhood, is caused by a mutation in the retinoblastoma tumor-suppressor gene RB. Retinoblastoma cells are thought to be resistant to transforming growth factor-beta (TGF-beta) because they do not express the TGF-beta type II receptor (TbetaR-II). In several tumor cell lines, trichostatin A (TSA), a potent inhibitor of histone deacetylase, induces expression of the TbetaR-II gene. The objective of the present study was to determine the effects of TSA on TbetaR-II gene expression in retinoblastoma cells. METHODS: Four retinoblastoma cell lines were transfected with a TbetaR-II promoter-luciferase reporter construct and analyzed for the effect of TSA on TbetaR-II mRNA expression, TbetaR-II promoter activity, transforming growth factor (TGF)-beta-related signal transduction, and cell growth using RT-PCR, Western blot analysis, chromatin immunoprecipitation, luciferase activity assay, and cell viability assays. RESULTS: TSA treatment induced the expression of TbetaR-II mRNA, activated the TbetaR-II promoter, and inhibited cell growth in the examined retinoblastoma cell lines. It did not restore TGF-beta-related signaling, however. CONCLUSIONS: These data show that TSA induces the expression of TbetaR-II mRNA and activates the TbetaR-II promoter in retinoblastoma cells. However, TSA treatment alone was insufficient to restore TGF-beta signaling in these cell lines. The inhibitory effect of TSA on cell growth may be unrelated to its effect on TbetaR-II expression.

Interactions between vitreous-derived cells and vascular endothelial cells in vitreoretinal diseases.

PURPOSE: This study aimed to investigate the roles played by vitreous-derived cells in the pathogenesis of vitreoretinal vascular diseases. METHODS: The vitreous was removed from porcine eyes and small pieces were cultured from which vitreous-derived cells were isolated. Polymerase chain reaction and ELISA were performed to determine the expression of vascular endothelial growth factor (VEGF) and interleukin 6 (IL-6) at the mRNA and protein levels, respectively. The viability of human retinal endothelial cells (HRECs) exposed to vitreous-derived cells was assessed by MTT assay. RESULTS: Expression of the mRNA and protein of VEGF and IL-6 was increased by exposing the porcine vitreous-derived cells (PVDCs) to interleukin-1alpha (IL-1alpha), interleukin-1beta (IL-1beta) and tumour necrosis factor alpha (TNFalpha), but not to VEGF or IL-6. The percentage of living human vascular endothelial cells was increased by including VEGF and IL-6 in the culture media. The viability of HRECs was affected by co-culturing them with PVDCs that had been exposed to IL-1alpha, IL-1beta, IL-6, TNFalpha and VEGF. CONCLUSIONS: Porcine vitreous-derived cells are stimulated by IL-1alpha, IL-1beta and TNFalpha, and produce VEGF and IL-6, which then enhance the proliferation of vascular endothelial cells. This network, including the cytokines and different types of cells, may contribute to the pathogenesis of proliferative vitreoretinal diseases.

Activin inhibits cell growth and induces differentiation in human retinoblastoma y79 cells.

PURPOSE: Activin is a member of the transforming growth factor-beta (TGF-beta) superfamily and exerts certain effects on differentiation and apoptosis. We investigated the effects of activin on retinoblastoma cell line. MATERIALS AND METHODS: We used retinoblastoma cell line Y79. Intracellular signal transduction of activin was investigated with RT-PCR, immunofluorescence study, and luciferase reporter assay. The effect of activin on cell growth was examined with fluorescence cell viability assays. To determine the effect of activin on apoptosis, a TUNEL assay and an immunofluorescence study of cleaved PARP were performed. The effect of activin on cell differentiation was examined with RT-PCR and Western blotting. RESULTS: Intracellular signal transduction of activin was confirmed in Y79 cells. Activin inhibited Y79 cell growth. Activin induced the expression of neural retina leucine zipper (Nrl) at the mRNA and protein levels. CONCLUSIONS: Nrl is a specific gene in rod photoreceptor development and is a gene indispensable to differentiation into rod photoreceptors, so the present results suggest that activin affects the differentiation of retinoblastoma cells into rod photoreceptor cells.

Effect of combined treatment with sub-Tenon injection of triamcinolone acetonide and photodynamic therapy in Japanese patients with age-related macular degeneration.

PURPOSE: To evaluate the benefit of the combination of a single sub-Tenon injection of triamcinolone acetonide (STTA) with photodynamic therapy (PDT) for the treatment of age-related macular degeneration (AMD) in Japanese patients. METHODS: The medical records of 111 eyes of 111 patients were reviewed retrospectively. Forty-five eyes underwent combined treatment with STTA and PDT, and 66 eyes underwent PDT alone. Time to vision loss, defined as a change of 0.3 or more logarithm of minimum angle of resolution (logMAR) units, and time to retreatment were evaluated using the Kaplan-Meier survival analyses. Cox regression models were used to estimate the hazard ratios for those end points to investigate clinical risk characteristics. RESULTS: Patients who underwent combined STTA with PDT had a significantly lower risk of retreatment than did those who underwent PDT alone (hazard ratio, 0.59; 95% confidence interval, 0.36-0.99). This beneficial association was found only in patients without polypoidal choroidal vasculopathy (PCV) lesions. However, combined treatment with STTA and PDT had no beneficial effect in reducing visual loss when compared with treatment with PDT alone. CONCLUSION: Combined treatment with STTA and PDT had a beneficial effect in reducing retreatment of AMD in Japanese patients. Those who had PCV lesions did not benefit from this additional treatment.

Two-year visual outcomes after photodynamic therapy in age-related macular degeneration patients with or without polypoidal choroidal vasculopathy lesions.

PURPOSE: To describe the visual outcomes 2 years after photodynamic therapy in Japanese patients with age-related macular degeneration (AMD) with or without polypoidal choroidal vasculopathy (PCV) lesions. METHODS: Sixty-three eyes of 63 consecutive patients with AMD or AMD + PCV who underwent photodynamic therapy were included in this study. Fluorescein and indocyanine green angiography were performed to diagnose AMD and AMD + PCV. Change in mean visual acuity and recurrence of active lesion during the follow-up period up to 2 years were assessed. RESULTS: Patients with typical AMD maintained visual acuity for 2 years after photodynamic therapy. For patients with AMD + PCV, the visual acuity was maintained during the first year but started decreasing by 0.09 logarithm of the minimum angle of resolution units per 3 months (95% confidence intervals [CI], 0.06-0.14) after 1 year. Moreover, patients with AMD + PCV had 82% higher risk of a recurrence of active lesions for each increase in 3 months of follow-up time after 1 year; this suggested that the risk of recurrence had increased later in follow-up after 1 year. Recurrence of active PCV lesions and massive subretinal hemorrhages were the main reasons for the late worsening of visual acuity. CONCLUSION: The visual acuity after photodynamic therapy in AMD patients was maintained for 2 years after the initial treatment. Patients with AMD + PCV had stable visual outcome within 1 year but not after 1 year; there are risks of late recurrences and massive hemorrhages after 1 year in patients with AMD + PCV.