Muh-Shy Chen

Prevalence and Risk Factors of Diabetic Retinopathy Among Noninsulin-dependent Diabetic Subjects

In a population-based study in Taiwan, 11,478 subjects aged 40 years or older were screened for diabetes in one urban and five rural areas. Among the 715 subjects proven to have diabetes, 527 subjects underwent ophthalmoscopy. Diabetic retinopathy was present in 184 of the 527 subjects (35.0%), including background diabetic retinopathy in 157 subjects (30.0%), preproliferative diabetic retinopathy in 15 subjects (2.8%), and proliferative diabetic retinopathy in 12 subjects (2.2%). Diabetic retinopathy was correlated with the duration of diabetes and age at onset of diabetes, type of diabetes treatment, higher serum creatinine levels, and lower serum cholesterol levels. Several other factors, including gender, age, residential area, family income, educational level, control and family history of diabetes, body mass index, physical activity, exercise, cigarette smoking, stroke, ischemic heart disease, leg vessel disease, hypertension, and proteinuria, had no significant association with retinopathy. By multiple logistic regression analysis, duration of diabetes was the most important risk factor related to retinopathy. Diabetic subjects treated with insulin had a higher risk of developing retinopathy than those treated with dietary control (relative risk, 1.57; .05 < P < .10). The univariate analysis disclosed that proliferative diabetic retinopathy was related to older age at examination, older age at onset of diabetes, type of diabetes treatment, and presence of leg vessel disease. Insulin-treated diabetic subjects also had a higher risk of proliferative diabetic retinopathy than patients in whom diabetes was controlled by diet, with a relative risk of 2.51 (.05 < P < .10) in the multiple logistic regression analysis.

Bevacizumab pretreatment in vitrectomy with silicone oil for severe diabetic retinopathy.

Purpose: To evaluate the effects of intravitreal bevacizumab pretreatment in vitrectomy with silicone oil infusion for severe diabetic retinopathy. Methods: Forty-one eyes (39 patients) that underwent primary vitrectomy with silicone oil tamponade for severe diabetic retinopathy were enrolled in this prospective, comparative case–control clinical study. Cases were alternately divided into the following Group 1, intravitreal bevacizumab (1.25 mg) injection 1 week before surgery; or Group 2, no bevacizumab injection. Cases were followed-up for at least 6 months. Postinjection retinal changes, intra- and postoperative findings, and outcomes were compared between groups. Results: Bevacizumab injections induced regression of neovascularization after 1 week. One case developed increased retinal detachment. In Group 1, there were significantly more cases of subretinal bleeding (P < 0.01). The severity of intraoperative and postoperative bleeding was significantly lower in Group 1. The blood reabsorption time was 11.1 ± 6.3 days in Group 1 and 34.8 ± 12.0 days in Group 2 (P < 0.01). One case in Group 1 and 2 cases in Group 2 had ultimate retinal detachment. Multiple regression analyses indicated bevacizumab significantly reduced intra- and postoperative bleeding. Conclusion: Bevacizumab may reduce intra- and postoperative hemorrhage in diabetic vitrectomy with silicone oil infusion. Increased subretinal bleeding are potential complications.

Malignant eyelid tumours in Taiwan

AbstractAims To describe the clinical characteristics of patients with eyelid cancers in Taiwan.Methods Between 1980 and 2000, 127 (58 males and 69 females) patients (mean age 62.6; range 10–91 years) with histologically confirmed eyelid cancers were retrospectively evaluated at the National Taiwan University Hospital and Far Eastern Memorial Hospital in Taiwan. Clinical data of all patients were reviewed from medical records. The mean follow-up period was 62.4 months (range 3–240) for 113 patients.Results The 127 eyelid cancers included 79 basal cell carcinomas (62.2%), 30 sebaceous gland carcinomas (23.6%), 11 squamous cell carcinomas (8.7%), five malignant melanomas (3.9%), one Kaposis sarcoma (0.8%), and one metastatic cancer (0.8%). Tumours developed more commonly in the lower (37.0%) than the upper eyelid (33.9%). The clinical accuracy in predicting eyelid malignancy was 90.5%. Primary treatment modality was mainly surgical excision. The recurrence, metastasis, and mortality rates at 5 years were 15.2, 11.7, and 7.3%, respectively, for all eyelid malignancies. Rates of sebaceous gland carcinoma recurrence, metastasis, and mortality were significantly higher (P<0.05) than those of basal cell carcinoma. The mean interval of recurrence or metastasis after primary treatment was 26.3 months (range 4–112) for all eyelid cancers.Conclusions Although basal cell carcinoma is the most common eyelid cancer in Taiwan, sebaceous gland carcinoma is also common. Of the two, basal cell carcinoma has a better prognosis and sebaceous gland carcinoma has a higher mortality and therefore should be treated much more aggressively. Long-term follow-up is needed after treatment of malignant eyelid tumours.

Foveola nonpeeling technique in internal limiting membrane peeling of myopic foveoschisis surgery.

Foveola Nonpeeling Technique in Internal Limiting Membrane Peeling of Myopic Foveoschisis Surgery Myopic foveoschisis is a unique complication of posterior staphyloma in highly myopic eyes. The formation of macular hole and posterior retinal detachment are well-known consequences of this unstable condition. Early stages of such degenerative changes can only be detected using the high-resolution imaging technique optical coherence tomography (OCT). Tangential traction is believed to be one of the main causes of the disease, along with anteroposterior traction. The significant role of vitreous and internal limiting membrane (ILM) traction is confirmed by the good results obtained by vitrectomy with gas tamponade and facedown positioning. However, postoperative development of full-thickness macular hole in some of the cases required surgery, jeopardizing the central fovea tissue, which existed preoperatively. The present report describes an ILM peeling technique that leaves the epifoveolar tissue in situ and thus prevents the development of macular hole.

Photodynamic Therapy With or Without Intravitreal Bevacizumab for Polypoidal Choroidal Vasculopathy: Two Years of Follow-Up

PURPOSE To compare the long-term results of the efficacy of photodynamic therapy (PDT) with or without intravitreal bevacizumab (IVB) injections for polypoidal choroidal vasculopathy. DESIGN Retrospective, comparative, interventional case series. METHODS We included 69 eyes of 69 patients with macula-involved polypoidal choroidal vasculopathy. All patients were followed up for more than 2 years. We compared the treatment outcomes between groups and investigated the factors influencing visual improvement at 24 months of follow-up. RESULTS Thirty-six patients received PDT combined with IVB and 33 patients received PDT monotherapy. At 3 months, the mean logarithm of minimal angle of resolution (logMAR) best-corrected visual acuity (BCVA) improved from 0.73 to 0.53 in the combined therapy group (P < .001) and from 0.79 to 0.72 in the PDT monotherapy group (P = .02), with a significant difference in treatment efficacy between the 2 groups (P < .001). However, the improvements in BCVA were not statistically significant after 21 months in the combined therapy group and 15 months in the monotherapy group. The difference in treatment efficacy between the 2 groups was not significant after 6 months. Initial BCVA (P = .005), lesion size (P = .011), patient age (P = .018), and location of polyps (P = .006) significantly predicted the final visual outcome rather than treatment modality (P = .243). CONCLUSIONS PDT combined with IVB for symptomatic PCV was temporarily superior to PDT monotherapy, and the treatment efficacy decreased with time. Initial BCVA, lesion size, and location were more significant than treatment modality as the factors influencing final visual improvement.

Development of Macrovascular Diseases in NIDDM Patients in Northern Taiwan: A 4-yr follow-up study

Objective— To assess the development of macrovascular diseases and explore major associative factors in NIDDM. Research Design and Methods— A total of 479 NIDDM patients ≥ 40 yr of age were recruited from four community primary care health centers of northern Taiwan in July 1986 for a cohort study with a 4-yr follow-up. No patient required insulin therapy within 1 yr of diagnosis nor had a history of diabetic ketoacidosis. All were able to participate independently in the activities of daily living. BP and ECG were measured, and a structured questionnaire was asked of each patient. Venous blood after overnight fasting was collected every year to measure cholesterol, HDL cholesterol, plasma glucose, and HbA1c. Results— The duration of diabetes was associated with the development of stroke with a relative risk of 1.063 for every 1-yr increment (P = 0.07). As for HVDs, the significant risk factors were serum cholesterol and HbA1c. For every 1-mg/dl increase in mean total cholesterol level, the relative risk of developing HVD increased 1.016-fold (P = 0.04). For every 1% increase in HbA1c, the relative risk of developing HVD increased 1.170-fold (P = 0.01). With regard to leg VDs, sex and cigarette smoking were significant risk factors. Women diabetic subjects had a higher relative risk than men. Cigarette smoking was significantly associated with leg VD with a relative risk of 6.9 for smokers compared with nonsmokers. The most significant risk factor for LVD was the total cholesterol level. For every 1-mg/dl increase in mean serum cholesterol level, the relative risk of LVD increased 1.013-fold. Conclusions— In the prevention of macrovascular diseases, effective intervention of the nondiabetic cardiovascular risk factors may be as important as or even more important than the good control of diabetes.

Intravitreal bevacizumab and panretinal photocoagulation for proliferative diabetic retinopathy associated with vitreous hemorrhage.

Purpose: To evaluate the efficacy of intravitreal bevacizumab with panretinal photocoagulation (PRP) in the treatment of proliferate diabetic retinopathy (PDR) with vitreous hemorrhage (VH). Methods: Forty cases (40 patients) with PDR and persistent VH were prospectively enrolled, with a follow-up period of 12 months or more. Intravitreal bevacizumab injection (1.25 mg) was given, followed by PRP when visualization of peripheral fundus could be obtained. A second injection was administered 4 weeks to 6 weeks after the first injection if no signs of VH decrease were noted. Vitrectomy was performed if VH persisted >12 weeks. The vitreous clear-up time (VCUT) and the rate of vitrectomy were compared with those in a historical control group (40 eyes in 40 patients) who were treated with conventional methods. Results: Thirty-one eyes had 1 injection and 9 eyes (22.5%) received 2 injections. Vitreous clear-up time in the study and control groups were 11.9 ± 9.5 weeks and 18.1 ± 12.7 weeks (P = 0.02), respectively. Rates of required vitrectomy were 10% in the study group and 45% in the control group (P = 0.01). Conclusion: One or 2 intravitreal injections of 1.25 mg bevacizumab with PRP are associated with rapid regression of VH and may reduce the need for vitrectomy.

Peripapillary intrachoroidal cavitation in high myopia: reappraisal

PurposeTo evaluate optical coherence tomography (OCT) and clinical findings of a peripapillary lesion in high myopia recently named peripapillary detachment in pathologic myopia (PDPM) or intrachoroidal cavitation.MethodsObservational case report by chart review, analysis of colour fundus photography, fluorescein angiography, and OCT in 16 eyes of 12 patients with myopic degeneration and the presence of a slightly elevated, patchy peripapillary, yellow-orange lesion on the fundus.ResultsPatients were mean age 53.1±10.7 years, with a spherical-equivalent refractive error of −10.99±3.33 D and mean axial length of 27.34±1.44 mm. The mean best-corrected visual acuity was log MAR 0.3±0.2 (between 20/100 and 20/20). Six eyes also showed myopic maculopathy. In 13 eyes, OCT showed an intrachoroidal hyporeflective space located below the normal plane of the retinal pigment epithelium. Six of these 13 eyes were found to have apparent communication between the intrachoroidal cavity and the vitreous space at the junction of the lesion and the myopic conus. In three eyes, OCT revealed intrachoroidal splitting. The fluorescein angiogram showed early hypofluorescence, without pooling or staining in late phase.ConclusionsThe yellow–orange elevated patchy lesions adjacent to the peripapillary conus in high myopic eyes may represent either intrachoroidal cavitation or choroidal schisis, which may be different stages of one disease spectrum. Vitreous fluid may be the source of the disruption of choroid and fluid accumulation.

Cyr61 induces the expression of monocyte chemoattractant protein-1 via the integrin ανβ3, FAK, PI3K/Akt, and NF-κB pathways in retinal vascular endothelial cells.

Diabetes causes a number of metabolic and physiological abnormalities in the retina. Many of the molecular and physiological abnormalities that develop during diabetic retinopathy are due to inflammation. Monocyte chemoattractant protein-1 (MCP-1) is an important factor involved in diabetic retinopathy. In a previous study, we found that cysteine-rich 61 (Cyr61), an important angiogenic factor, also plays an important role in diabetic retinopathy. In addition to the direct effects of Cyr61, we observed that Cyr61 can induce the expression of MCP-1. However, the mechanism through which this occurs is not completely understood in chorioretinal vascular endothelial cells. We therefore investigated the effects of Cyr61 on MCP-1 expression in this cell type. Cyr61 stimulated the expression of MCP-1 at the mRNA, protein, and secreted protein levels in a dose-dependent and time-dependent manner. Both total MCP-1 levels and secreted MCP-1 levels were attenuated during the response to Cyr61 stimulation by pretreatment with integrin ανβ3-blocking antibodies, a FAK inhibitor (PF573228), a PI3K inhibitor (LY294002), and an Akt inhibitor (A6730). Electrophoretic mobility shift assays revealed that the above inhibitors suppressed the activation of NF-κB. Additionally, deletion of the NF-κB-binding element in the MCP-1 gene promoter led to a decrease in expression in luciferase reporter assays. These results show that the induction of MCP-1 by Cyr61 is mediated through the activation of the integrin ανβ3, FAK, PI3K/Akt, and IKK/NF-κB pathways in chorioretinal vascular endothelial cells.

Cysteine-rich 61, a member of the CCN family, as a factor involved in the pathogenesis of proliferative diabetic retinopathy.

PURPOSE Cysteine-rich 61 (Cyr61/CCN1) is reported to mediate angiogenesis. In this study, its role in ocular angiogenesis and proliferative diabetic retinopathy (PDR) was investigated. METHODS The effects of Cyr61 were evaluated by determining proliferation and chemotaxis and in an assay of capillary tube formation in synthetic matrix by chorioretinal endothelial cells (RF/6A). In the same cells, Cyr61 expression under hypoxic conditions was then investigated. Interactions between Cyr61 and vascular endothelial growth factor (VEGF) were examined using endothelial cell chemotaxis, tube-formation assay, and cross-stimulation assay. A mouse model of oxygen-induced retinopathy (OIR) and a rat model of streptozocin-induced diabetes were used to evaluate Cyr61 expression in the retina. Cyr61 levels were also measured and chemotactic effects were evaluated in vitreous samples from patients with PDR. RESULTS Cyr61 significantly induced proliferation, migration, and synthetic matrix tube formation of RF/6A cells. Hypoxia significantly induced Cyr61 mRNA and protein expression. Cyr61 induced expression of VEGF and vice versa. Anti-Cyr61 or anti-VEGF could inhibit the effects of both Cyr61 and VEGF. Intravitreal injection of anti-Cyr61 antibody significantly inhibited retinal neovascularization in the mouse OIR model. Cyr61 mRNA and protein were significantly expressed in the retina of streptozocin-induced diabetic rats. Vitreous levels of Cyr61 were elevated in patients with PDR when compared with nondiabetic patients. CONCLUSIONS Cyr61 acts as an angiogenic mediator of ocular neovascularization in vitro and in vivo. It may interact with VEGF in a synergetic manner. Vitreous levels of Cyr61 are elevated in PDR, and it may play an important role in the diseases pathogenesis.