Venous Sinus Stenting for Transverse Sinus Stenosis Associated with Leptomeningeal Carcinomatosis in a Patient with Epidermal Growth Factor Receptor-Mutated Lung Cancer: A Case Report.

BACKGROUND Cerebral venous sinus obstruction associated with leptomeningeal carcinomatosis is an extremely rare complication of advanced non-small-cell lung cancer. There is little information available on the efficacy of therapeutic options because of its rarity and extremely poor prognosis. CASE REPORT A 57-year-old man presented with severe headache, vomiting, and visual loss for 1 month. Head magnetic resonance venography (MRV) showed occlusion of the left transverse sinus. Gd-enhanced MRI showed no abnormal enhancement. Lumbar puncture intracranial pressure was higher than 40 cmH2O. Positive cerebrospinal fluid tumor cytology confirmed the diagnosis of leptomeningeal carcinomatosis (LC). The headache was relieved by repeated lumbar punctures, and ventriculo-peritoneal shunt was performed. Cerebral angiography showed severe stenosis of the left transverse sinus without thrombosis, and significant delay of cerebral circulation. The transverse sinus stenosis was judged to be contributing to raised intracranial pressure, and the patient underwent left transverse sinus stent placement. After the procedure, his visual acuity improved, the visual field was enlarged, and his headache could be controlled by medication. Follow-up Gd-enhanced MRI showed dural enhancement and spinal dissemination. Because molecular biology of the surgical specimen showed epidermal growth factor receptor (EGFR)-activating mutations, he was treated with osimertinib for 2 months. He survived for 8 months following the diagnosis of LC and left transverse sinus stenosis. CONCLUSIONS Venous sinus stenting can offer an effective palliative interventional option for symptom relief of severe headache and visual symptoms, even in the end stage of malignancy.

Intra-familial Similarity of Wide-Field Fundus Autofluorescence in Inherited Retinal Dystrophy.

To examine the similarity of wide-field fundus autofluorescence (FAF) imaging in inherited retinal dystrophy between siblings and between parents and their children. The subjects included 17 siblings (12 with retinitis pigmentosa and 5 with cone rod dystrophy) and 10 parent-child pairs (8 with retinitis pigmentosa and 2 with cone rod dystrophy). We quantified the similarity of wide-field FAF using image processing techniques of cropping, binarization, superimposition, and subtraction. The estimated similarity of the siblings was compared with that of the parent-child pairs and that of the age-matched unrelated patients. The similarity between siblings was significantly higher that of parent-child pairs or that of age-matched unrelated patients (P = 0.004 and P = 0.049, respectively). Wide-field FAF images were similar between siblings with inherited retinal dystrophy but different between parent-child pairs. This suggests that aging is a confounding factor in genotype-phenotype correlation studies.

Radial fundus autofluorescence in the periphery in patients with X-linked retinitis pigmentosa.

PURPOSE: To describe the peripheral autofluorescence images and clinical features of patients with retinal dystrophy who showed radial fundus autofluorescence (FAF) at the posterior pole. METHODS: The authors retrospectively reviewed pooled wide-field FAF images of 711 patients with retinal dystrophy and 56 family members. RESULTS: Eleven eyes of seven women exhibited radial FAF at the posterior pole. Wide-field FAF showed extension of the radial pattern to the periphery in all eyes except one. One woman showed radial hyper-FAF only in the periphery, not at the posterior pole. These eight individuals were X-linked retinitis pigmentosa patients or carriers. The tapetal-like reflex was not observed in their color fundus photographs. The peripheral visual field showed wedge-shaped restriction in some individuals. CONCLUSION: Wide-field FAF imaging can depict radial FAF not only at the posterior pole but also in the periphery in X-linked retinitis pigmentosa carriers. The authors therefore agree with previous reports that radial FAF may be a hallmark of X-linked retinitis pigmentosa.

Association of retinal vessel attenuation with visual function in eyes with retinitis pigmentosa.

PURPOSE: To investigate the association between visual changes and retinal vessel attenuation in patients with retinitis pigmentosa (RP). DESIGN: A retrospective, longitudinal, observational cohort study. METHODS: We analyzed 45 eyes from 45 subjects who were followed-up for ≥3 years at our clinic. Using the computer-based Interactive Vessel Analysis program, central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) were determined. Age- and sex-matched controls from normal subjects were selected from our archived fundus photograph library. Visual acuity, visual field area (Goldmann perimetry, V4e white test light), mean deviation (Humphrey perimetry, central 10-2 program), and central macular thickness (optical coherence tomography) were analyzed for correlations with CRAE and CRVE. RESULTS: Both CRAE and CRVE were significantly decreased in RP eyes (94.9±13.5 µm and 155.6±20.0 µm, respectively) compared with control eyes (138.1±14.7 µm and 215.0±20.4 µm, respectively, both P<0.001). After 3 years of follow-up, visual field area was associated with both CRAE (r=0.584, P<0.01) and CRVE (r=0.500, P=0.008). A significant association was also observed between mean deviation and CRAE (r=0.298, P=0.047). In eyes with RP, a narrower vessel caliber at baseline was associated with a larger decline in visual acuity over the 3-year follow-up interval (CRAE: r=-0.344, P=0.021; CRVE: r=-0.314, P=0.035). CONCLUSION: Retinal vessel caliber is associated with some visual functions in patients with RP.

Wide-field fundus autofluorescence abnormalities and visual function in patients with cone and cone-rod dystrophies.

PURPOSE: To evaluate the clinical utility of wide-field fundus autofluorescence (FAF) in patients with cone dystrophy and cone-rod dystrophy. METHODS: Sixteen patients with cone dystrophy (CD) and 41 patients with cone-rod dystrophy (CRD) were recruited at one institution. The right eye of each patient was included for analysis. We obtained wide-field FAF images using a ultra-widefield retinal imaging device and measured the area of abnormal FAF. The association between the area of abnormal FAF and the results of visual acuity measurements, kinetic perimetry, and electroretinography (ERG) were investigated. RESULTS: The mean age of the participants was 51.4 ± 17.4 years, and the mean logarithm of the minimum angle of resolution was 1.00 ± 0.57. The area of abnormal FAF correlated with the scotoma measured by the Goldman perimetry I/4e isopter (ρ = 0.79, P < 0.001). The area also correlated with amplitudes of the rod ERG (ρ = -0.63, P < 0.001), combined ERG a-wave (ρ = -0.72, P < 0.001), combined ERG b-wave (ρ = -0.66, P < 0.001), cone ERG (ρ = -0.44, P = 0.001), and flicker ERG (ρ = -0.47, P < 0.001). CONCLUSIONS: The extent of abnormal FAF reflects the severity of functional impairment in patients with cone-dominant retinal dystrophies. Fundus autofluorescence measurements are useful for predicting retinal function in these patients.

Prevalence and spatial distribution of cystoid spaces in retinitis pigmentosa: investigation with spectral domain optical coherence tomography.

PURPOSE: To investigate the prevalence and spatial distribution of cystoid spaces (CS) in retinitis pigmentosa patients with spectral domain optical coherence tomography. METHODS: A total of 529 eyes of 275 patients with retinitis pigmentosa were examined with spectral domain optical coherence tomography. The presence or absence of CS was judged for each eye. Retinal layer and outer retinal status where the CS existed were also investigated. Statistical analysis was performed using 1 eye per 1 patient. RESULTS: Cystoid spaces were present in 119 of 529 eyes (22.5%) of 74 of 275 patients (26.9%). There were no significant differences between the cases with and without CS except for central foveal thickness (P < 0.001). Cystoid spaces were noted in the inner nuclear layer in almost all eyes (98.6%), and outer nuclear layer/outer plexiform layer was also involved in many eyes (27.8%). Cystoid spaces were sometimes seen in ganglion cell layer (6.9%). Cystoid spaces were predominantly (78.9%) distributed in the relatively preserved retina where external limiting membrane was retained. The presence of epiretinal membrane or posterior vitreous adhesion was associated with the presence of CS (P < 0.001) but showed no relationship with the spatial location of CS (P = 1.000). CONCLUSION: The prevalence of CS in patients with retinitis pigmentosa was 26.9% and contrary to previous reports, most CS were present in inner nuclear layer. In addition, most CS were observed in relatively retained retina, which is compatible to the prevailing notion. Epiretinal membrane or posterior vitreous adhesion was also associated with the development of CS. The distribution of CS in inner and preserved retina may provide insight for the pathogenesis of CS in retinitis pigmentosa.

Tomographic comparison of cone-rod and rod-cone retinal dystrophies.

PURPOSE: To investigate the relationship between impairment of cone/rod photoreceptors and changes in optical coherence tomography (OCT) findings. METHODS: We retrospectively reviewed the clinical records of 35 patients with cone-rod dystrophy (CRD) and 35 visual acuity-matched patients with retinitis pigmentosa (RP). The presence or absence of the external limiting membrane (ELM), inner segment ellipsoid (ISe), interdigitation zone (IZ), and foveal cavitation (hyporeflective space in the outer retina) were determined using OCT image evaluation. RESULTS: There were no statistical differences in the number of CRD and RP patients with an intact ELM and ISe. None of the CRD patients had an intact IZ, but 20 % of RP patients did (P = 0.011). In addition, foveal cavitation tended to be observed more frequently in CRD patients than (25.7 %) in RP patients (5.7 %) despite the difference not being significant after the correction of multiple comparison. CONCLUSIONS: Eyes with CRD and RP had significant differences in foveal morphology, even when visual acuity was matched. This result supports the notion that absence of an IZ and the presence of foveal cavitation is related to cone-dominant photoreceptor impairment.

Clinical and immunological characterization of paraneoplastic retinopathy.

PURPOSE: To report the clinical and immunological characterization of paraneoplastic retinopathy (PR) and to investigate the association between spectral-domain optical coherence tomography (SDOCT) findings and the targets of autoantibodies in PR. METHODS: We retrospectively enrolled eight patients (age range, 57-85 years; four men and four women) suspected of having PR. All patients underwent comprehensive ophthalmic examinations, including best-corrected visual acuity (BCVA) measurement, slitlamp examinations, kinetic visual field testing with Goldmann perimetry, electroretinography (ERG), fundus photography, fluorescein angiography, fundus autofluorescence (FAF), SDOCT, and serum sample tests (Western blot analysis and immunohistochemistry [IHC]). RESULTS: Three patients had a history of malignant tumors, and four patients were newly diagnosed as having neoplastic tumors (small cell lung carcinoma [SCLC], thymoma, pancreatic neuroendocrine neoplasm, and colon cancer). Another de novo malignancy (SCLC) was detected in a patient with a history of malignancy (bladder cancer and liposarcoma). The BCVA in these patients ranged from hand motion to 1.5. Goldmann perimetry revealed island, ring-shaped, concentric, or central scotoma. All patients showed nonrecordable or reduced amplitude results on ERG. Fluorescein leakage was detected in five patients. Hyperautofluorescence and/or hypoautofluorescence on FAF was detected in six patients. The serum sample tests identified anti-retinal antibodies in all patients. Patients whose serum contained anti-photoreceptor or anti-retinal pigment epithelium antibody on IHC showed damage of the outer retina on SDOCT. CONCLUSIONS: In this case series, PR was associated with a variety of neoplasms and autoantibodies. Spectral-domain OCT can be used to characterize morphologic changes, and the changes were associated with the targets of autoantibodies.

Wide-field fundus autofluorescence imaging of retinitis pigmentosa.

PURPOSE: To evaluate the clinical usefulness of wide-field fundus autofluorescence (FAF) imaging in patients with retinitis pigmentosa (RP). DESIGN: Cross-sectional case series. PARTICIPANTS: Seventy-five eyes of 75 patients with RP. METHODS: We examined the eyes of the RP patients using the Optos 200Tx imaging system (Optos PLC, Dunfermline, United Kingdom) and identified abnormal FAF patterns such as ring hyperautofluorescence and patchy hypoautofluorescent areas. Patients with hyperautofluorescent rings or foveal hyperautofluorescence were compared with those without such findings. We determined the percentage area occupied by the FAF abnormalities within a defined region of the eye and examined the relationship between the percentage area of these abnormalities and the visual field area. Moreover, we categorized the patients into 3 different groups based on the presence of a patchy hypoautofluorescent lesion larger than 1 disc diameter: Group A consisted of those with patchy lesions smaller than 1 disc diameter, group B consisted of those with patchy lesions larger than 1 disc diameter but present in only 1 quadrant, and group C consisted of those with patchy lesions larger than 1 disc diameter and present in more than 1 quadrant. In addition, various clinical characteristics were compared among these 3 groups. MAIN OUTCOME MEASURES: Predicting the visual field size and duration of the disease in RP patients based on FAF patterns. RESULTS: Patients without hyperautofluorescent rings or foveal hyperautofluorescence had better visual acuity or mean deviation measured with a Humphrey perimeter. The total area of the abnormal FAF image correlated with the visual field area measured with a Goldmann perimeter (R = -0.64, P<0.001). The individuals with the large patchy hypofluorescent areas (i.e., larger than 1 disc diameter) were older than those with small patchy hypofluorescent areas (group A vs. groups B and C, P = 0.002 and P<0.001, respectively) and had experienced the symptoms for longer durations (group A vs. groups B and C, P<0.05 and P<0.001, respectively). CONCLUSIONS: We can estimate the visual field in patients with RP using the objective measurements from wide-field FAF. The presence of patchy hypofluorescent lesions can be used an indicator of the duration of RP. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Concentric division of 10° visual field tests in retinitis pigmentosa.

PURPOSE: The purpose of this study was to estimate the optimal size of visual field test for detecting longitudinal changes in retinitis pigmentosa (RP) by dividing the visual field. METHODS: We reviewed the results of 10° static visual field tests in 19 eyes of 19 RP patients. Sixty-eight numeric value points were divided into two area types: concentric areas (A1, A1-2, A1-3, A1-4, A1-5, A1-6) and circular areas (A1, A2, A3, A4, A5, A6). Serial values of mean sensitivity in each area of each patient were analyzed by linear regression. RESULTS: Analysis of the concentric areas showed that 10 of 19 eyes had the best R (2) value in the most central area, A1. Analysis of circular areas showed that 7 of 19 eyes had the steepest slope of decline in A1. The inner-segment/outer-segment (IS/OS) line was significantly shorter in eyes with low variability and evident disease progression in the inner areas than the ones in the outer areas. CONCLUSIONS: The optimal size of monitoring RP progression was different in each case and may depend on the remaining morphology of the outer retina.

[Genotype screening of retinal dystrophies in the Japanese population using a microarray].

PURPOSE: To investigate the pathogenic variants of retinal dystrophies in the Japanese population using microarray analysis. SUBJECTS AND METHODS: DNA extracted from the blood samples of 84 families (87 patients) with retinal dystrophies (retinitis pigmentosa, Leber congenital amaurosis, cone-rod dystrophy and Bietti's crystalline retinopathy) was screened by Asper Biotech services. All the variants detected by microarray analysis were verified by direct sequencing. RESULTS: Mutations were detected in 2 of 36 families with autosomal dominant retinitis pigmentosa, 2 of 4 with Leber congenital amaurosis, 11 of 24 with cone-rod dystrophy, 3 of 7 with macular dystrophy and 6 of 7 with Bietti's crystalline retinopathy. CONCLUSION: Genotype screening using microarray analysis can be effectively used to determine the variants of retinal dystrophies, except retinitis pigmentosa, in the Japanese population.

Outer retinal circular structures in patients with Bietti crystalline retinopathy.

BACKGROUND: Bietti crystalline retinopathy (BCR) is a distinct retinal degenerative disease characterised by retinal degeneration with many yellow-white crystals located mainly at the posterior pole area. Using spectral domain-optical coherence tomography (SD-OCT), the structural change in retina was investigated. METHODS: Patients diagnosed with BCR (n=12), retinitis pigmentosa (RP, n=292) and cone dystrophy (n=16) were included in this study. The authors mainly examined fundus photographs and SD-OCT, infrared and fundus autofluorescence images of these patients. RESULTS: Crystalline deposits were detected in portions of the retinal pigment epithelium that lacked patchy degenerated lesions. SD-OCT revealed that most of the observed crystalline deposits were located adjacent to the inner side of retinal pigment epithelium layer. The change most frequently observed was circular hyper-refractive structures in the outer nuclear layer. Although the structures were considered to be previously reported "tubular formation" or "tubular degeneration", we determined that many of these circular structures were slices of spherical structures and were typically noted in areas suspected of ongoing active degeneration. CONCLUSION: BCR has characteristic structures in the outer nuclear layer. Although the incidence of the structure varies, it may be characteristic of retinal degeneration and can be found in many retinal degenerative diseases.

Novel role of erythropoietin in proliferative diabetic retinopathy.

Diabetic retinopathy is a leading cause of visual disturbance in adults. In proliferative diabetic retinopathy, ischemia-induced pathologic growth of new blood vessels often causes catastrophic loss of vision. Besides VEGF, the existence of another potent ischemia-induced angiogenic factor is postulated. Since ischemia-inducible erythropoietin (Epo) has recently been identified its angiogenic properties, we investigated its potential role during retinal angiogenesis in proliferative diabetic retinopathy (PDR). The vitreous Epo level in patients with PDR was significantly higher than that in nondiabetic patients. Multivariate logistic regression analyses indicated that Epo and VEGF were independently associated with PDR and that Epo was more strongly associated with PDR than VEGF. Blockade of Epo inhibits retinal neovascularization in vivo, and inhibits endothelial cell proliferation response to PDR vitreous in vitro. Our data provide strong evidence that erythropoietin is a potent retinal angiogenic factor independent of VEGF and is capable of stimulating ischemia-induced retinal angiogenesis in proliferative diabetic retinopathy. Inhibition of such molecular mechanisms in the retinal angiogenesis could be a new therapeutical strategy in halting or preventing pathologic angiogenesis in diabetic retinopathy.

Time-lapse imaging of vitreoretinal angiogenesis originating from both quiescent and mature vessels in a novel ex vivo system.

PURPOSE: Diabetic retinopathy (DR) is an angiogenic disease that leads to severe visual loss. However, adequate animal models of vitreoretinal neovascularization in proliferative diabetic retinopathy (PDR) have not yet been described. The purpose of this study was to develop a novel ex vivo system for assessing vitreoretinal angiogenic processes that originate from both quiescent and mature vessels that could be observed with time-sequential imaging. METHODS: The retinas of 7- to 8-week-old mice were cultured for 4 days, with or without several growth factors with novel procedures, and immunohistochemistry was performed. The retinas from Tie2-GFP mice were cultured with vascular endothelial growth factor (VEGF), and time-sequential imaging of vitreoretinal angiogenesis was acquired. RESULTS: Vascular sprouts were induced by both VEGF and placenta growth factor, but not by insulin-like growth factor-1, basic fibroblast growth factor or angiopoietin-2. In explants with or without VEGF, perivascular mural cells were dissociated from endothelial cells, which is an important step during angiogenesis and in the progression of DR. Furthermore, use of time-lapse observations of retinal neovascularization events visualized that the first step in vascular sprout emergence from quiescent vessels was a single cell extension. The leading edges of a sprouting endothelial cell extended and retracted in a sequential manner. From newly formed vessels, additional vascular sprouts then emerged and new vessels fused to each other, resulting in vascular branching. CONCLUSIONS: Time-lapse imaging of this system visualized the dynamic process in vitreoretinal neovascularization from quiescent and mature vessels.

EphrinA1 inhibits vascular endothelial growth factor-induced intracellular signaling and suppresses retinal neovascularization and blood-retinal barrier breakdown.

The Eph receptor/ephrin system is a recently discovered regulator of vascular development during embryogenesis. Activation of EphA2, one of the Eph receptors, reportedly suppresses cell proliferation and adhesion in a wide range of cell types, including vascular endothelial cells. Vascular endothelial growth factor (VEGF) plays a primary role in both pathological angiogenesis and abnormal vascular leakage in diabetic retinopathy. In the study described herein, we demonstrated that EphA2 stimulation by ephrinA1 in cultured bovine retinal endothelial cells inhibits VEGF-induced VEGFR2 receptor phosphorylation and its downstream signaling cascades, including PKC (protein kinase C)-ERK (extracellular signal-regulated kinase) 1/2 and Akt. This inhibition resulted in the reduction of VEGF-induced angiogenic cell activity, including migration, tube formation, and cellular proliferation. These inhibitory effects were further confirmed in animal models. Intraocular injection of ephrinA1 suppressed ischemic retinal neovascularization in a dose-dependent manner in a mouse model. At a dose of 125 ng/eye, the inhibition was 36.0 +/- 14.9% (P < 0.001). EphrinA1 also inhibited VEGF-induced retinal vascular permeability in a rat model by 46.0 +/- 10.0% (P < 0.05). These findings suggest a novel therapeutic potential for EphA2/ephrinA1 in the treatment of neovascularization and vasopermeability abnormalities in diabetic retinopathy.

Erythropoietin as a retinal angiogenic factor in proliferative diabetic retinopathy.

BACKGROUND: Although vascular endothelial growth factor (VEGF) is a primary mediator of retinal angiogenesis, VEGF inhibition alone is insufficient to prevent retinal neovascularization. Hence, it is postulated that there are other potent ischemia-induced angiogenic factors. Erythropoietin possesses angiogenic activity, but its potential role in ocular angiogenesis is not established. METHODS: We measured both erythropoietin and VEGF levels in the vitreous fluid of 144 patients with the use of radioimmunoassay and enzyme-linked immunosorbent assay. Vitreous proliferative potential was measured according to the growth of retinal endothelial cells in vitro and with soluble erythropoietin receptor. In addition, a murine model of ischemia-induced retinal neovascularization was used to evaluate erythropoietin expression and regulation in vivo. RESULTS: The median vitreous erythropoietin level in 73 patients with proliferative diabetic retinopathy was significantly higher than that in 71 patients without diabetes (464.0 vs. 36.5 mIU per milliliter, P<0.001). The median VEGF level in patients with retinopathy was also significantly higher than that in patients without diabetes (345.0 vs. 3.9 pg per milliliter, P<0.001). Multivariate logistic-regression analyses indicated that erythropoietin and VEGF were independently associated with proliferative diabetic retinopathy and that erythropoietin was more strongly associated with the presence of proliferative diabetic retinopathy than was VEGF. Erythropoietin and VEGF gene-expression levels are up-regulated in the murine ischemic retina, and the blockade of erythropoietin inhibits retinal neovascularization in vivo and endothelial-cell proliferation in the vitreous of patients with diabetic retinopathy in vitro. CONCLUSIONS: Our data suggest that erythropoietin is a potent ischemia-induced angiogenic factor that acts independently of VEGF during retinal angiogenesis in proliferative diabetic retinopathy.

Angiopoietin-1 attenuates H2O2-induced SEK1/JNK phosphorylation through the phosphatidylinositol 3-kinase/Akt pathway in vascular endothelial cells.

Oxidative stress activates various signal transduction pathways, including Jun N-terminal kinase (JNK) and its substrates, that induce apoptosis. We reported here the role of angiopoietin-1 (Ang1), which is a prosurvival factor in endothelial cells, during endothelial cell damage induced by oxidative stress. Hydrogen peroxide (H2O2) increased apoptosis of endothelial cells through JNK activation, whereas Ang1 inhibited H2O2-induced apoptosis and concomitant JNK phosphorylation. The inhibition of H2O2-induced JNK phosphorylation was reversed by inhibitors of phosphatidylinositol (PI) 3-kinase and dominant-negative Akt, and constitutively active-Akt attenuated JNK phosphorylation without Ang1. These data suggested that Ang1-dependent Akt phosphorylation through PI 3-kinase leads to the inhibition of JNK phosphorylation. H2O2-induced phosphorylation of SAPK/Erk kinase (SEK1) at Thr261, which is an upstream regulator of JNK, was also attenuated by Ang1-dependent activation of the PI 3-kinase/Akt pathway. In addition, Ang1 induced SEK1 phosphorylation at Ser80, suggesting the existence of an additional signal transduction pathway through which Ang1 attenuates JNK phosphorylation. These results demonstrated that Ang1 attenuates H2O2-induced SEK1/JNK phosphorylation through the PI 3-kinase/Akt pathway and inhibits the apoptosis of endothelial cells to oxidative stress.

Efficacy of surgical removal of the internal limiting membrane in diabetic cystoid macular edema.

PURPOSE: To evaluate the efficacy of surgical removal of the internal limiting membrane (ILM) in diabetic cystoid macular edema (CME). METHODS: Prospective, noncomparative, interventional case series including 21 eyes of 18 consecutive patients with diabetic CME. Vitrectomy with separation of the posterior hyaloid and induction of posterior vitreous detachment had been performed previously on nine eyes. Pars plana vitrectomy for removal of the ILM was performed. RESULTS: CME resolved in eyes that underwent initial vitrectomy and in those with long-standing (>1 year) CME after previous vitrectomy. Postoperative best-corrected visual acuity improved by >/=2 lines of a Snellen equivalent in 14 eyes (67%) (P < 0.01). The mean foveal thickness (distance between the inner retinal surface and the retinal pigment epithelium) decreased from 553 microm to 221 microm at 4 weeks (P < 0.001). No recurrences or deterioration of CME was observed during the entire follow-up period (mean, 17.8 months; range, 8-34 months). CONCLUSION: Surgical removal of the ILM might be an effective procedure for reducing CME in patients with diabetes. A prospective, randomized, controlled study is necessary to further evaluate the efficacy of the procedure.

Vitreous levels of angiopoietin 2 and vascular endothelial growth factor in patients with proliferative diabetic retinopathy.

PURPOSE: To investigate the levels of angiopoietin-2 (Ang2) and vascular endothelial growth factor (VEGF) in the vitreous fluids of patients with proliferative diabetic retinopathy (PDR) and to ascertain their involvement, if any, in angiogenesis of PDR. DESIGN: Retrospective case-control study. METHODS: Forty-one eyes of 41 patients with proliferative diabetic retinopathy and 18 eyes of 18 patients with nondiabetic ocular diseases (control group). Nondiabetic control eyes included 11 with idiopathic macular hole and 7 with idiopathic epiretinal membrane. Vitreous fluid samples were obtained at vitrectomy, and the levels of Ang2 and VEGF were measured by enzyme-linked immunosorbent assay. RESULTS: Vitreous level (mean +/- SD) of Ang2 was significantly higher in patients with PDR (1,753 +/- 3,213 pg/ml) than in control patients (112 +/- 113 pg/ml) (P < .0001). The vitreous concentration of VEGF was also significantly higher in patients with PDR (812 +/- 1,108 pg/ml) than in control patients (1.7 +/- 4.4 pg/ml) (P < .0001). Both Ang2 and VEGF levels in eyes with active PDR were significantly higher than in those with inactive PDR. The vitreous concentration of Ang2 correlated significantly with that of VEGF in eyes with proliferative diabetic retinopathy ([correlation coefficient] rho = 0.497, P = .001). CONCLUSIONS: These data demonstrate an increase of Ang2 in the vitreous fluid of patients with PDR and suggest an association of Ang2 and VEGF with angiogenic activity in PDR.