RETINAL BLOOD FLOW AFTER INTRAVITREAL BEVACIZUMAB IS A PREDICTIVE FACTOR FOR OUTCOMES OF MACULAR EDEMA ASSOCIATED WITH CENTRAL RETINAL VEIN OCCLUSION.

PURPOSE: To investigate whether retinal blood flow levels after intravitreal bevacizumab (IVB) treatment are correlated with the outcomes of patients with macular edema secondary to central retinal vein occlusion. METHODS: This retrospective observational case study enrolled 44 cases nonischemic central retinal vein occlusion. In each patient, visual acuity, central retinal thickness, and mean blur rate, which was measured by laser speckle flowgraphy and represents retinal blood flow velocity, were examined. RESULTS: At the end of the follow-up period (19.8 ± 8.8 months), 4 of 44 eyes (9.1%) converted to the ischemic type (converted group), whereas 40 (90.9%) remained unchanged (nonischemic group). Mean central retinal thickness significantly decreased and mean visual acuity significantly improved at 1 month after the first IVB injection in each group. Mean mean blur rate in the nonischemic group significantly increased, whereas it was unchanged in the converted group. The difference between the two groups was already significant after the first IVB injection. Subsequently, visual acuity worsened in the converted group. Multiple linear regression analysis indicated that the strongest correlation was between the last visual acuity and the last mean blur rate. CONCLUSION: Blood flow measurements are useful for evaluating IVB treatments. Blood flow after IVB can predict outcomes in patients with central retinal vein occlusion.

Visual outcomes and prognostic factors in open-globe injuries.

BACKGROUND: Ocular trauma is an important cause of visual loss worldwide. Improvements in our knowledge of the pathophysiology and management of ocular trauma during the past 30 years, in conjunction with advances in the instrumentation and techniques of ocular surgery, have improved the efficacy of vitreoretinal surgery in injured eyes. The aim of the current study was to determine the visual outcomes and prognostic factors of open-globe injuries in the Japanese population. METHODS: Retrospective study of 59 eyes of 59 patients presented with open globe injuries between September 2008 and March 2014 at Nagasaki University Hospital was conducted. Demographic factors including age, gender, and clinical data such as cause of injury, presenting visual acuity (VA), location of injury, type of injury, lens status, presence of intraocular foreign body, types of required surgeries, and final VA were recorded. According to the classification of Ocular Trauma Classification Group, wound location was classified into three zones. Chi-square test was used to compare presented data. RESULTS: Out of the 59 patients, 46 were placed in the Light Perception (LP) group, and 13 were placed in the No Light Perception (NLP) group. Work-related trauma was the most common cause (27 eyes) followed by falls (19eyes). Work-related trauma was common in males (P = 0.004), while falls was significantly common in females (P = 0.00001). Zone III injuries had statistically significantly poor prognostic factor compared to other zones (P = 0.04). All cases of NLP group (100%) presented with rupture globe. Poor VA at first visit (P = 0.00001), rupture globe (P = 0.026), history of penetrating keratoplasty (PK) (P = 0.017), retinal detachment (RD) (P = 0.0001), vitreous hemorrhage (VH) (P = 0.044), and dislocation of crystalline lens (P = 0.0003) were considered as poor prognostic factors. CONCLUSION: Poor VA at first visit, rupture globe, zone III injuries, history of penetrating keratoplasty, RD, VH, and dislocation of crystalline lens were found to be poor prognostic factors. PPV had a good prognostic value in open globe injuries associated with posterior segment involvement.

RETINAL BLOOD FLOW CORRELATES TO AQUEOUS VASCULAR ENDOTHELIAL GROWTH FACTOR IN CENTRAL RETINAL VEIN OCCLUSION.

PURPOSE: As laser speckle flowgraphy can measure blood flow distribution in the ocular fundus, the authors analyzed the relationship between retinal blood flow and aqueous vascular endothelial growth factor (VEGF) concentration in central retinal vein occlusion. METHODS: This prospective observational study examined 45 eyes of 45 patients with central retinal vein occlusion before treatment. Blood flow in large vessels around and at the optic disk, aqueous VEGF concentration, and arteriovenous passage time were examined. Blood flow was evaluated as mean blur rate by laser speckle flowgraphy. RESULTS: Fluorescein angiography found 20 ischemic and 25 nonischemic type eyes. Aqueous VEGF concentration in the ischemic type was significantly higher than that in the nonischemic type (P = 0.01). Arteriovenous passage time was significantly correlated to the logarithm of the aqueous VEGF concentration (P = 0.0001). Mean blur rate of the affected eye/mean blur rate of the unaffected eye of the ischemic type was significantly lower than the nonischemic type (P = 0.039). Additionally, mean blur rate was significantly correlated both to the logarithm of the aqueous VEGF concentration (P < 0.0001) and to the arteriovenous passage time (P = 0.0001). CONCLUSION: Laser speckle flowgraphy may be useful for predicting aqueous VEGF concentration and severity of central retinal vein occlusion.

Increased annexin A2 expression in the placenta of women with acute worsening of preeclampsia.

BACKGROUND: The aims of present study were to investigate the expression of Annexin A2 in the placenta of patients with preeclampsia (PE) and correlate these data with acute worsening of clinical symptoms. METHODS: Placentas were collected from uncomplicated normal pregnancies (n = 9), PE cases without emergency termination of pregnancy (group 1, n = 6), and PE cases with acute worsening of symptoms necessitating immediate pregnancy termination (group 2, n = 7). Immunohistochemistry data were analyzed quantitatively, and placental mRNA expression was measured by Real-time PCR. RESULTS: Group 2 had a significantly shorter interval between diagnosis and pregnancy termination compared with group 1 (p = 0.002). Birth weight and placental weight in group 2 were significantly lower compared with the normal group (p = 0.006 and p = 0.03, birth weight and placental weight, respectively), whereas there were no differences in gestational age at delivery between the three groups or the severity of high blood pressure and proteinuria between the PE groups. Placental expression of Annexin A2 as determined by immunohistochemistry was significantly higher in both PE groups compared with the uncomplicated pregnancy group (p < 0.001 and p < 0.001, groups 1 and 2, respectively). Placental Annexin A2 mRNA expression was significantly elevated in group 2 compared with the normal group (p = 0.002) but did not change in group 1. CONCLUSIONS: This study is the first to demonstrate increased placental Annexin A2 mRNA expression during the acute phase of PE. Immunohistochemical staining of placental Annexin A2 was high, regardless of PE phase. These findings suggest that worsening of PE might alter Annexin A2 expression at the transcription level.

Treatment of diabetic macular edema in real-world clinical practice: The effect of aging.

AIMS/INTRODUCTION: In older patients, the management of diabetic macular edema (DME) can be complicated by comorbidities, geriatric syndrome, and socioeconomic status. This study aims to evaluate the effects of aging on the management of DME. MATERIALS AND METHODS: This is a real-world clinical study including 1,552 patients with treatment-naïve center-involved DME. The patients were categorized into 4 categories by age at baseline (C1, <55; C2, 55-64; C3, 65-74; and C4, ≥75 years). The outcomes were the change in logarithm of the minimum angle of resolution best-corrected visual acuity (logMAR BCVA) and central retinal thickness (CRT), and the number of treatments from baseline to 2 years. RESULTS: From baseline to 2 years, the mean changes in logMAR BCVA from baseline to 2 years were -0.01 in C1, -0.06 in C2, -0.07 in C3, and 0.01 in C4 (P = 0.016), and the mean changes in CRT were -136.2 µm in C1, -108.8 µm in C2, -100.6 µm in C3, and -89.5 µm in C4 (P = 0.008). Treatments applied in the 2 year period exhibited decreasing trends with increasing age category on the number of intravitreal injections of anti-VEGF agents (P = 0.06), selecting local corticosteroid injection (P = 0.031), vitrectomy (P < 0.001), and laser photocoagulation outside the great vascular arcade (P < 0.001). CONCLUSIONS: Compared with younger patients with DME, patients with DME aged ≥75 years showed less frequent treatment, a lower BCVA gain, and a smaller CRT decrease. The management and visual outcome in older patients with DME would be unsatisfactory in real-world clinical practice.

Retinal Vascular Resistance Significantly Correlates With Visual Acuity After 1 Year of Anti-VEGF Therapy in Central Retinal Vein Occlusion.

Purpose: To investigate whether the resistivity of all retinal vessels, termed total capillary resistance (TCR), after anti-vascular endothelial growth factor (VEGF) treatment was correlated with the outcomes of patients with macular edema secondary to central retinal vein occlusion (CRVO). Methods: In total, 67 patients with nonischemic CRVO were enrolled in this retrospective observational case series. In each patient, we examined visual acuity; central retinal thickness (CRT); mean blur rate (MBR), which represents retinal blood flow velocity; and TCR. MBR and TCR were measured by laser speckle flowgraphy. Results: During the 1-year follow-up period, nine of 67 eyes (13.4%) converted to the ischemic type (converted group), whereas 58 eyes (86.6%) remained unchanged (nonischemic group). Mean CRT significantly decreased in all groups; however, the mean visual acuity significantly improved only in the nonischemic group. Mean MBR significantly increased in the nonischemic group but remained unchanged in the converted group. Mean TCR was significantly reduced in the nonischemic group but remained unchanged in the converted group. Multiple linear regression analysis revealed that MBR and TCR were the independent factors with the strongest and second strongest correlations with visual acuity after treatment, respectively. Conclusions: These findings suggest that measurements of the independent factors MBR and TCR are useful for evaluating anti-VEGF treatments in patients with CRVO. Translational Relevance: Development of clinically relevant technologies.

Retinal Microvascular Resistance Estimated from Waveform Analysis Is Significantly Higher With a Threshold Value in Central Retinal Vein Occlusion.

Purpose: Evaluation of blood flow is useful for understanding the severity of central retinal vein occlusion (CRVO). Actual blood flow may be determined by the resistivity of the retinal vein in CRVO. We have previously evaluated mean blur rate (MBR) to reflect total retinal blood flow velocity in CRVO cases using laser speckle flowgraphy (LSFG). This study evaluated retinal total vascular resistance in CRVO cases using the new index of total capillary resistance (TCR) from LSFG. Methods: We measured the TCR of 68 CRVO patients who visited Nagasaki University Hospital between 2009 and 2016 and 42 age-matched controls without systemic disease. We compared TCRs among control eyes, CRVO fellow eyes, and CRVO affected eyes. A CRVO threshold value was then obtained from the receiver operating characteristic curve. Results: MBR was significantly lower for CRVO affected eyes (20.3 ± 8.2) than for control eyes (37.5 ± 8.4; P < 0.01) and CRVO fellow eyes (36.4 ± 10.0; P < 0.01, Dunn's test). TCR was significantly higher for CRVO affected eyes (1.20 ± 0.55) than for control eyes (0.68 ± 0.2; P < 0.01) and CRVO fellow eyes (0.81 ± 0.28; P < 0.01, Dunn's test). The threshold for the presence of CRVO was 0.93 and area under the curve was 0.84. Conclusions: By measuring TCR in addition to MBR, more detailed information regarding CRVO pathology can be obtained. Translational Relevance: Comparison of values before and after treatment may be useful for evaluating the effects of treatment.

An adult case of parainfectious optic neuritis associated with genital herpes simplex virus type 2 infection.

Although acute retinal necrosis (ARN) and optic neuritis following herpes encephalitis are known causes of acute visual impairment associated with herpes simplex virus (HSV) infection, there have been no reports of parainfectious optic neuritis associated with genital HSV type 2 (HSV-2) infection. A young Japanese woman developed unilateral optic neuritis 7 days after the onset of genital HSV-2 infection. Ophthalmologic examination revealed no findings suggestive of ARN and both multiple sclerosis and neuromyelitis optica were ruled out by the brain images and serum antibody testing. An oral steroid therapy improved her symptoms. Here, we describe the first case of parainfectious optic neuritis associated with genital HSV-2 infection.

Real-world management of treatment-naïve diabetic macular oedema in Japan: two-year visual outcomes with and without anti-VEGF therapy in the STREAT-DME study.

BACKGROUND/AIMS: To investigate real-world outcomes for best-corrected visual acuity (BCVA) after 2-year clinical intervention for treatment-naïve, centr-involving diabetic macular oedema (DME). METHODS: Retrospective analysis of longitudinal medical records obtained from 27 institutions specialising in retinal diseases in Japan. A total of 2049 eyes with treatment-naïve DME commencing intervention between 2010 and 2015 who were followed for 2 years were eligible. Interventions for DME included anti-vascular endothelial growth factor (VEGF) therapy, local corticosteroid therapy, macular photocoagulation and vitrectomy. Baseline and final BCVA (logMAR) were assessed. Eyes were classified by the treatment pattern, depending on whether anti-VEGF therapy was used, into an anti-VEGF monotherapy group (group A), a combination therapy group (group B) and a group without anti-VEGF therapy (group C). RESULTS: The mean 2-year improvement of BCVA was -0.04±0.40 and final BCVA of >20/40 was obtained in 46.3% of eyes. Based on the treatment pattern, there were 427 eyes (20.9%) in group A, 807 eyes (39.4%) in group B and 815 eyes (39.8%) in group C. Mean improvement of BCVA was -0.09±0.39, -0.02±0.40 and -0.05±0.39, and the percentage of eyes with final BCVA of >20/40 was 49.4%, 38.9%, and 52.0%, respectively. CONCLUSION: Following 2-year real-world management of treatment-naïve DME in Japan, BCVA improved by 2 letters. Eyes treated by anti-VEGF monotherapy showed a better visual prognosis than eyes receiving combination therapy. Despite treatment for DME being selected by specialists in consideration of medical and social factors, a satisfactory visual prognosis was not obtained, but final BCVA remained >20/40 in half of all eyes.

Real-world management of treatment-naïve diabetic macular oedema: 2-year visual outcome focusing on the starting year of intervention from STREAT-DMO study.

BACKGROUND/AIMS: To investigate the yearly change of real-world outcomes for best corrected visual acuity (BCVA) after 2-year clinical intervention for treatment-naïve diabetic macular oedema (DMO). METHODS: Retrospective analysis of aggregated, longitudinal medical records obtained from 27 retina specialised institutions in Japan from Survey of Treatment for DMO database. A total of 2049 treatment-naïve centre involving DMO eyes of which the initial intervention started between 2010 and 2015, and had been followed for 2 years, were eligible. As interventions, antivascular endothelial growth factor (VEGF) agents, local corticosteroids, macular photocoagulation and vitrectomy were defined. In each eye, baseline and final BCVA, the number of each intervention for 2 years was extracted. Each eye was classified by starting year of interventional treatment. RESULTS: Although baseline BCVA did not change by year, 2-year improvement of BCVA had been increased, and reached to +6.5 letters in the latest term. There is little difference among starting year about proportions of eyes which BCVA gained >15 letters, in contrast to those which lost >15 letters were decreased by year. The proportion of eyes receiving anti-VEGF therapy was dramatically increased, while those receiving the other therapies were gradually decreased. The proportion of eyes which maintained socially good vision of BCVA>20/40 has been increased and reached to 59.0% in the latest term. CONCLUSION: For recent years, treatment patterns for DMO have been gradually but certainly changed; as a result, better visual gain, suppression of worsened eyes and better final BCVA have been obtained. Anti-VEGF therapy has become the first-line therapy and its injection frequency has been increasing.

Uterine artery flow velocity waveforms during uterine contractions: differences between oxytocin-induced contractions and spontaneous labor contractions.

AIM: To clarify the effects on uterine arterial flow velocity waveforms of uterine contractions following oxytocin infusion and during spontaneous labor. METHODS: Uterine arterial flow velocity waveforms were obtained by pulsed Doppler methods from 22 women during an oxytocin challenge test (OCT), 26 women during oxytocin-induced labor, and 40 women during spontaneous labor. Mean resistance index (RI) for bilateral arteries was used for analyses. After the onset of labor, flow velocity waveforms were assessed according to cervical dilatation. During OCT, Doppler flow velocimetry was performed when three uterine contractions occurred per 10-min period. RESULTS: RI values did not differ significantly between induced and spontaneous labor during relaxations at any level of cervical dilatation. However, during contractions, RI was significantly higher for induced labor than for spontaneous labor. Absence or reversal of flow was more frequent in the OCT group than in the induced labor group (P < 0.0001). However, no significant differences were found between spontaneous and induced labor groups. CONCLUSION: Interactions between the contracting uterine body and the relaxing lower segment in oxytocin-induced labor might be associated with differences in uterine arterial flow during contraction between oxytocin-induced and spontaneous labor. However, changes in the intensity of uterine contractions during labor progression might differ between oxytocin-induced and spontaneous labor.

Acceleration time of fetal arterial blood flow velocity waveforms: a preliminary study.

BACKGROUND: Doppler ultrasonography has been widely used for fetal estimation, but most of them were estimated by the resistance and pulsatility indices. Acceleration time is one of parameters of flow velocity waveforms, but only few reports had discussed acceleration time of fetal circulation. METHODS: We analyzed Doppler flow velocity waveforms of fetal middle cerebral artery, descending aorta and abdominal umbilical artery obtained from 70 normal pregnant women between 18 and 40 weeks. Acceleration time was cross-sectionaly examined throughout pregnancy course. RESULTS: The acceleration times revealed no remarkable changes throughout pregnancy course in the middle cerebral artery, but significant increases were observed in the acceleration time of the descending aorta between 18-23 and 24-32 weeks. It also significantly decreased after 33 weeks compared to that of 18-32 weeks in the umbilical artery. CONCLUSIONS: The acceleration time in fetal descending aorta is significantly shorter than that in the abdominal umbilical artery between 18 and 32 weeks of gestation. The umbilical arterial acceleration time apparently decreases throughout pregnancy course. Its values are almost double for that in the descending aorta between 18 and 23 weeks, but it becomes to be equal to the aortic acceleration time. The continuous decrease of the umbilical arterial acceleration time might be a result of a relative increase of placental flow.

Protein S deposition at placenta: a possible role of protein S other than anticoagulation.

Protein S is an antithrombotic cofactor for protein C that also has multifunctional anti-inflammatory, cellular protective, apoptotic and mitogenic properties. Protein S levels are thought to decrease during pregnancy, but the underlying mechanism remains unknown. We compared protein S concentrations throughout normal pregnancy with those of nonpregnant women and measured plasma C4b-binding protein levels in nonpregnant women and in pregnant women at the 40th gestational week. We also examined protein S and C4b-binding protein in the placenta by immunohistochemical staining at early (20th gestational week) and late (40th gestational week) stages of pregnancy. Plasma protein S activity and free protein S-antigen levels significantly decreased from the 10th gestational week and total protein S antigen decreased from the 20th. C4b-binding protein levels between pregnant and nonpregnant women did not significantly differ. The stainable portion of protein S was located at the fetomaternal interface, particularly at degenerative villi. C4b-binding protein was weakly stained at the same areas as protein S. Neither protein S nor C4b-binding protein were stained at normal villi. These results indicated that protein S can protect or restore damaged villi via a physiological effect in addition to its anticoagulation properties.

Oral kallidinogenase improved visual acuity and maintained chorioretinal blood flow levels after treatment for diabetic macular edema.

PURPOSE: This study was designed to investigate the therapeutic effects of oral kallidinogenase medication as an adjuvant therapy in treating patients with diabetic macular edema (DME). STUDY DESIGN: This was a prospective, open-labeled, randomized study. METHODS: All patients were given posterior sub-Tenon triamcinolone acetonide (STTA) injection and focal laser treatment session for DME. The patients were subdivided into two groups: 1) those treated with oral kallidinogenase for at least 6 months after local treatment (treated group) and 2) those treated without oral kallidinogenase (untreated group). In this study, best-corrected visual acuity (BCVA), central retinal thickness (CRT), subfoveal choroidal thickness (SCT), and chorioretinal blood flow level were measured in 17 patients (19 eyes). Chorioretinal blood flow levels at the disc and macula were measured by laser speckle flowgraphy and evaluated using the mean blur rate (MBR). These data were measured at baseline and at 1, 3, and 6 months after treatment initiation. RESULTS: BCVA at 6 months after treatment significantly improved in treated group (P<0.05). But the mean CRT after treatment significantly decreased in both groups. There was no significant difference in the mean SCT at baseline between the two groups. The mean SCT after treatment in treated group was significantly thinner than that before treatment (P<0.05). Compared to baseline (100%), MBR at the disc and the macula at 6 months after treatment significantly decreased to 84.8% and 86.2%, respectively, in untreated group (P<0.05), though it remained unchanged at 98.7% and 99.7% in treated group. CONCLUSION: Oral kallidinogenase medication is useful as an adjuvant therapy to enhance the therapeutic effect of STTA in DME patients.

Cyclic stretch and hypertension increase retinal succinate: potential mechanisms for exacerbation of ocular neovascularization by mechanical stress.

PURPOSE: We investigated succinate metabolism in cells undergoing clinically relevant cyclic stretch and in spontaneously hypertensive rat (SHR) retina. METHODS: We seeded ARPE-19 cells on 6-well BioFlex collagen I-coated, silicone elastomer-bottomed culture plates. Cells then were subjected to pulsatile stretch using a computer-controlled vacuum stretch apparatus. A physiologic stretch frequency of 60 cycles per minute and 5% to 15% prolongation of the elastomer-bottomed plates were used. Succinate concentration was assessed by enzymatic analysis and high-performance liquid chromatography-mass spectrometry. The VEGF was measured using enzyme-linked immunosorbent assays. The 12-week-old male SHRs and weight-matched Wistar-Kyoto (WKY) control rats were treated with or without 100 mg·kg(-1)·day(-1) captopril for 1 week. The vitreous body and retina of each rat were extracted after 1 week of therapy, and the vitreoretinal succinate concentration was measured. RESULTS: Cells exposed to cyclic stretch accumulated intracellular succinate in a time- and magnitude-dependent manner, and also accumulated VEGF protein levels. Moreover, BAPTA/AM, an intracellular calcium chelate reagent, significantly inhibited the stretch-induced succinate increase. After cyclic stretch, levels of intracellular fumarate, a citric acid cycle intermediate, also were significantly increased compared to controls. The BAPTA/AM inhibited this increase. For the in vivo experiments, hypertension increased vitreoretinal succinate and fumarate in SHRs compared to the normotensive WKY controls. When hypertension was reduced using captopril, vitreoretinal succinate returned to baseline levels. CONCLUSIONS: These findings suggest that cyclic stretch and hypertension increased intracellular succinate in cultured retinal pigment epithelial cells and the vitreoretinal succinate of SHRs through a calcium-dependent pathway.

Retinal blood flow levels measured by laser speckle flowgraphy in patients who received intravitreal bevacizumab injection for macular edema secondary to central retinal vein occlusion.

PURPOSE: To report retinal blood flow levels measured by Laser speckle flowgraphy in three patients after they received an intravitreal bevacizumab injection (IVB) for macular edema secondary to central retinal vein occlusion (CRVO). METHODS: Three patients (3 eyes) being treated with IVB (1.25 mg/0.05 mL) for secondary macular edema of CRVO were examined. Laser speckle flowgraphy analyses of the blood flow were based on the examinations of mean blur rate (MBR) at the major vessels of the optic disk. Central retinal thickness (CRT) was measured by optical coherence tomography using Macular Cube 512 × 128 scanning protocol. RESULTS: After the first IVB, Case 1 exhibited an increase in MBR and decrease in CRT. After 4 months, an additional injection was required because of a subsequent MBR decrease and CRT increase, which led to an increase in MBR and decrease in CRT similar to that observed after the first treatment. Subsequently, blood flow has continued to improve without additional IVB. Macular edema recurrence in Case 2 led to 3 further IVBs over a 6-month period. Although increases in MBR and decreases in CRT were noted, MBR values tended to decline after each IVB. In Case 3, macular edema recurrence led to 5 additional IVBs being carried out within a 1-year period. Continuous MBR increases and CRT decreases were observed in the patient after each IVB. By measuring MBR using laser speckle flowgraphy, we may predict the prognosis of CRVO. CONCLUSION: Mean blur rate increases after IVB were confirmed by laser speckle flowgraphy in three patients. Even though CRVO pathology backgrounds can vary, laser speckle flowgraphy may be useful in both determining the CRVO prognosis and in evaluating treatment efficacy.

Pregnancy complicated by cervical varix and low-lying placenta: a case report.

We present a case of cervical varix and low-lying placenta. A cesarean section was performed because of the risk of bleeding with vaginal delivery; hemostasis was achieved using z sutures at the bleeding points. After delivery, the cervical varix decreased dramatically in size. It is important to recognize the clinical features and available treatments for cervical varix.

Succinate increases in the vitreous fluid of patients with active proliferative diabetic retinopathy.

PURPOSE: To examine vitreous succinate levels from proliferative diabetic retinopathy (PDR) patients and ascertain their association with PDR activity. DESIGN: Comparative case series. METHODS: A total of 81 eyes of 72 PDR patients were divided into active PDR (22 eyes), quiescent PDR (21 eyes), and active PDR with intravitreal bevacizumab injection (38 eyes). Twenty epiretinal membrane (ERM) patients (21 eyes) served as controls. RESULTS: Mean vitreous succinate levels were 1.27 µM in ERM and 2.20 µM in PDR, with the differences statistically significant (P = .03). When comparing mean vitreous succinate levels (active PDR: 3.32 µM; quiescent PDR: 1.02 µM; active PDR with intravitreal bevacizumab injection: 1.20 µM), significant differences were found between active and quiescent PDR (P < .01) and between active PDR and active PDR with intravitreal bevacizumab injection (P < .01). Even though succinate levels were low, retinopathy activities were very high in patients with active PDR with intravitreal bevacizumab injection. Mean vitreous vascular endothelial growth factor (VEGF) levels (active PDR: 1696 pg/mL; quiescent PDR: 110 pg/mL; active PDR with intravitreal bevacizumab injection: n.d.) were similar to previous reports. Mean vitreous erythropoietin levels (active PDR: 703 mIU/mL; quiescent PDR: 305 mIU/mL; active PDR with intravitreal bevacizumab injection: 1562 mIU/mL) suggested very high retinopathy activities in patients with active PDR with intravitreal bevacizumab injection. CONCLUSIONS: Succinate, like VEGF, may be an angiogenic factor that is induced by ischemia in PDR. Although succinate is reported to promote VEGF expression, VEGF inhibition decreases succinate. Thus, VEGF, via a positive feedback mechanism, may regulate succinate.

Spontaneous dislocation of in-the-bag intraocular lens primarily in cases with prior vitrectomy.

PURPOSE: To report cases of late onset spontaneous in-the-bag dislocation of the intraocular lens (IOL) and to compare these results with past reports. METHODS: We retrospectively studied 21 eyes of 18 patients with dislocation of the entire capsular bag containing the IOL. Gender, age, interval between original surgery and IOL dislocation, and the predisposing factors were examined. Cases occurring after trauma were excluded. RESULTS: The mean ± SD age of the 12 men (57.1%) and 9 women included in the study was 67.8 ± 8.6 years at the time of the IOL removal procedure. The interval between the original surgery and the IOL dislocation was 7.9 ± 8.6. Associated clinical conditions included vitrectomy in 8 eyes (40.0%) of 7 patients, high myopia in 3 eyes (14%) of 2 patients, uveitis in 2 eyes (9.5%) of 2 patients, retinitis pigmentosa in 2 eyes (9.5%) of 1 patient, and pseudoexfoliation in 1 eye (4.8%) of 1 patient. There was no identifiable associated condition in 2 eyes (9.5%) of 2 patients, who were comparatively younger than the other cases. This result differs from previously published reports that have found a higher frequency of pseudoexfoliation and lower frequency of prior vitrectomy. CONCLUSIONS: In-the-bag IOL dislocation was frequently associated with prior vitrectomy and sometimes occurred without specific conditions.