Voxel-based morphometry reveals altered gray matter volume related to cognitive dysfunctioning in neovascular glaucoma patients.

We used correlation analysis to examine whether changes in grey matter volume in patients correlated with clinical presentation. gray matter volume was markedly reduced in neovascular glaucoma patients than healthy controls in the following brain regions: left cingulum anterior/medial frontal gyrus; left middle frontal gyrus, orbital part; left inferior frontal gyrus, orbital part; superior temporal gyrus/right frontal inferior orbital part. VBM directly suggests that neovascular glaucoma patients have changed in the volume of multiple brain regions. These changes exist in brain areas related to the visual pathway, as well as other brain areas which are not related to vision. The alteration of specific brain areas are closely related to clinical symptoms such as increased intraocular pressure and optic nerve atrophy in neovascular glaucoma patients. In conclusion, neovascular glaucoma may cause paralgesia, anxiety, and depression in patients.

Radiation-induced neovascular glaucoma: A devastating disease.

Neovascular glaucoma (NVG) is a potentially blinding form of secondary glaucoma, with radiation being one of the rare causes. This report is aimed to discuss a case of NVG caused secondary to radiotherapy (RT) given for a nasal malignancy. A 50-year-old male presented with enophthalmos, dry eye, and NVG 3 years after receiving RT for chondrosarcoma of nasal and paranasal cavities. He was given topical antiglaucoma medications, retinal laser, and intravitreal bevacizumab injection and thus prevented the eye from becoming a painful blind eye. The radiation oncologist and ear, nose, and throat specialists have to liaise closely with ophthalmologist when patients receive radiation involving the eye in the treatment field to prevent, diagnose, and treat this devastating condition.

In vivo antivascular endothelial growth factor treatment induces corneal endothelium apoptosis in rabbits through changes in p75NTR-proNGF pathway.

Intravitreal injection (IVT) of antivascular endothelial growth factor (anti-VEGF) agents is widely used for the treatment of retinal vascular diseases. Recently, the injection of anti-VEGF agents in the ocular anterior chamber has been proposed for the treatment of neovascular glaucoma and potential side effects on the corneal structures have been investigated with contrasting results. Increasing evidence has demonstrated that VEGF inhibition is associated with cellular apoptotic changes and that this effect may be mediated by alterations in nerve growth factor (NGF) pathway. In this study, we demonstrated that anterior chamber injection (IC), but not IVT injection of two different anti-VEGF agents, aflibercept and ranibizumab, affects rabbit corneal endothelium in terms of survival and apoptosis and is associated with changes in endothelial expression of NGF precursor (proNGF) and p75 neurotrophin receptor (p75NTR) receptor. We observed an increase in corneal endothelial cell incorporation of trypan blue and expression of cleaved-caspase 3 (c-Casp3), p75NTR, and RhoA after IC injection of both anti-VEGF drugs when compared with the vehicle. Our results showed that apoptosis induction by aflibercept was more pronounced when compared with that of ranibizumab. Aflibercept also mediated a significant increase in endothelial expression of proNGF when compared with the vehicle. In line with these data, IC administration of both anti-VEGF agents induced the activation of apoptotic signals in endothelial cells, including an increase in c-Casp3, decrease in Bad Ser 112 phosphorylation, and unbalance of AKT phosphorylation. These results demonstrated that administration of anti-VEGF in the anterior chamber of rabbit affects endothelial cell survival by inducing apoptosis through alteration of NGF pathway.

Pars plana insertion of glaucoma shunt in eyes with refractory neovascular glaucoma: Case report.

RATIONALE: Neovascular glaucoma (NVG) is one of the most aggressive types of glaucoma in clinical practice. The outcomes are unsatisfactory despite the successful trabeculectomy with glaucoma shunt insertion. PATIENT CONCERNS: EX-PRESS Glaucoma Filtration Device (Alcon Laboratories, Fort Worth, TX), which is used in open-angle glaucoma surgery, could minimize the potential injury caused by traditional trabeculectomy. However, no study reported about the posterior segment insertion of this device. This article reports an alternative surgical technique and outcomes of pars plana insertion of glaucoma shunt in a patient with refractory NVG. DIAGNOSES: This research was a retrospective study of a patient with refractory NVG and in whom trabeculectomy with EX-PRESS implantation was performed. However, bleb failure developed three times in four years. INTERVENTIONS: In this patient, the previous EX-PRESS shunt was retrieved and reinserted into the posterior segment through the pars plana 3.5 mm behind the limbus. OUTCOMES: The post-operation intraocular pressure was stable for more than eight months after surgery without any surgical intervention or antiglaucoma medication use. No discomfort nor major complication was observed after this operation. LESSONS: Pars plana insertion of glaucoma shunt may provide an alternative to treat refractory NVG in patients who had received pars plana vitrectomy.

Iris Thickness and Severity of Neovascular Glaucoma Determined Using Swept-Source Anterior-segment Optical Coherence Tomography.

PURPOSE: To investigate the iris thickness (IT) in neovascular glaucoma (NVG) using swept-source anterior-segment optical coherence tomography (ASOCT). PATIENTS AND METHODS: In this retrospective, clinic-based, comparative study, we enrolled 20 NVG patients [11 with 360-degree angle-closure (AC)-NVG and 9 with NVG without AC] and 14 healthy age-matched controls. Horizontal scanning images of swept-source ASOCT were analyzed using software calipers in temporal and nasal angle areas. ITs at 1 and 2 mm from the pupil edge were measured using ASOCT. The relation between IT and the severity of NVG, the effects of intraocular pressure (IOP), intravitreal antivascular endothelial growth factor (anti-VEGF) injection, and panretinal photocoagulation (PRP) were assessed using linear regression analysis based on the corrected Akaike information criteria index. RESULTS: The IT was thinner in 360-degree AC-NVG patients, followed by NVG patients without AC and controls (0.33 vs. 0.48 vs. 0.57 mm at 1 mm and 0.31 vs. 0.43 vs. 0.49 mm at 2 mm; P<0.001 by ANOVA). Multiple linear regression analysis revealed that 360-degree AC-NVG patients-NVG patients without AC and controls (coefficient: -0.16), NVG patients without AC-control (-0.13) and underwent PRP (0.23) at 1 mm, 360-degree AC-NVG patients-NVG patients without AC and controls (-0.12), NVG patients without AC-controls (-0.08), underwent PRP (0.16), received anti-VEGF injection (0.05) and IOP (-0.001) at 2 mm were selected predictors to explain IT. CONCLUSIONS: IT decreases with the progression of the NVG stage and is thinnest in 360-degree AC-NVG patients. Our study suggests a new morphologic feature of NVG.

Management of neovascular glaucoma with intravitreal ranibizumab, panretinal photocoagulation, and subsequent 5-fluorouracil augmented trabeculectomy: A case report.

RATIONALE: Neovascular glaucoma (NVG) is one of the most refractory types of glaucoma caused by high ischemic retinal disorders, resulting in severe visual loss. Intravitreal injections of ranibizumab have been reported to have anatomical and functional success in treating NVG. PATIENT CONCERNS-DIAGNOSES-INTERVENTIONS: We report a case with neovascular glaucoma due to central retinal vein occlusion who received combination therapy with intravitreal ranibizumab (IVR) injection, panretinal photocoagulation (PRP) and subsequent 5-fluorouracil (5-FU) augmented trabeculectomy. OUTCOMES: One week after IVR injection, the intraocular pressure (IOP) had partially decreased to 33 mmHg, and there was a complete regression of neovascularization of the iris (NVI) and the angle (NVA). PRP was feasible after IVR due to improvement of corneal edema which made an adequate view of the posterior pole of fundus. The surgery of trabeculectomy with 5-FU was performed 2 weeks after IVR to control the IOP. The intraoperative and postoperative courses were uneventful without any adverse complication. Post trabeculectomy, his vision remained stable and the IOP was in the range of 4-15 mmHg without topical antiglaucoma medications. A functioning bleb was maintained and there was no recurrence of NVI and NVA during the complete follow-up period of 6 months. LESSONS: Combined treatment of IVR, PRP, and subsequent 5-FU augmented trabeculectomy is demonstrated to be a possible new paradigm for the management of advanced NVG with angle closure and intractable elevation of IOP.

Role of Platelet Parameters on Neovascular Glaucoma: A Retrospective Case-Control Study in China.

PURPOSE: Retinal vein occlusion (RVO) and diabetic retinopathy (DR) are two major sight-threatening diseases which may lead to neovascular glaucoma (NVG). The aim of this study was to explore the association between platelet parameters and NVG. METHODS: A total of 185 subjects were enrolled for the study from January, 2012 to December, 2015 at the Eye-ENT Hospital of Fudan University. Patients include those with NVG secondary to RVO (RVO group, n = 38), patients with NVG secondary to DR (DR group, n = 47), diabetics mellitus without retinopathy (DM group, n = 52), and healthy individuals (control group, n = 48). A complete ophthalmological examination including visual field examination, A-scan ultrasound, Fundus photography, and measurement of platelet parameters were performed for NVG subjects. RESULTS: There was no statistical difference in the mean age and gender among the RVO, DR, and control groups (p>0.05). The mean level of platelet distribution width (PDW) was higher (p<0.001) in the RVO group (15.16±2.13fl) and DR group (16.17±1.66fl) when compared with the control group (13.77±2.99fl). The mean plateletcrit (PCT) value of the RVO group (0.229±0.063%) was also higher (p = 0.049) than the control group (0.199±0.045). In the DR group, mean platelet volume (MPV) value (10.72±1.57fl) was significantly higher (p = 0.002) than the control group (9.75±0.89fl). A similar trend was observed when platelet parameters were compared among the 3 groups with respect to age. The mean level of PDW was significantly higher (p<0.001) in the DR group (16.17±1.66fl) compared with the DM group (13.80±3.32fl). Stepwise multiple logistic regression analysis revealed that PDW (OR = 1.44, 95%CI = 1.149-1.805, p = 0.002) and MPV (OR = 1.503, 95%CI = 1.031-2.192, p = 0.034) were associated with the DR group, PDW (OR = 1.207, 95%CI = 1.010-1.443, p = 0.039) and PCT (OR = 1.663, 95%CI = 1.870-2.654, p = 0.036) were associated with the RVO group. CONCLUSION: Our results suggest that increased PDW and MPV are associated with the NVG secondary to DR group, elevated PDW and PCT are associated with the RVO group. It indicates that platelets might be an important factor in the onset and/or development of NVG.

[Effect of Intravitreal Bevacizumab Injection on Iris and Iridocorneal Angle Neovascularization in Neovascular Glaucoma].

Neovascular glaucoma is a serious complication associated with retinal ischemic changes, which increase the production of vascular endothelial growth factor. Vascular endothelial growth factor has been implicated as a key molecule in the development of newly formed vessels and neovascular glaucoma. Intravitreal injection of bevacizumab, a full-length humanized anti-vascular endothelial growth factor monoclonal antibody, leads to a dramatic regression of the new iris and iridocorneal angle vessels on slitlamp examination. However, anterior segment angiography reveals that bevacizumab does not cause a regression of the neovascular vessels themselves but reduces vascular permeability while newly formed vessels are still present in the iris and iridocorneal angle. This review focuses on the pathology and diagnosis of neovascula glaucoma and the effect of intravitreal bevacizumab on the iris and iridocorneal angle neovascularization.

Clinical and histological characteristics of canine ocular gliovascular syndrome.

OBJECTIVE: To characterize the clinical, diagnostic, and histopathologic findings in dogs with canine ocular gliovascular syndrome (COGS). PROCEDURES: The archives at the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) were used to identify eyes with COGS. Histopathological inclusion criteria included: a neovascular membrane extending from the optic nerve head or retina, clusters of spindle cells lacking vascularization within the vitreous, and histological signs of glaucoma. Special and immunohistochemical (IHC) staining techniques were performed. Clinical data, treatments, and outcomes were obtained from case records and information provided by submitting veterinarians. RESULTS: Thirty-seven eyes of 36 dogs were identified with COGS. The average age at diagnosis was 8.8 years (±2.2). The relative risk for a Labrador retriever affected by COGS was significantly greater (9.3 times) (P < 0.0001) when compared to all other dog breeds within the COPLOW database. Most dogs presented with hyphema and secondary glaucoma; average intraocular pressure was 39 mmHg (±19). Average time to enucleation or evisceration was 27 days. Vitreal cells stained positive with IHC for glial fibrillary acidic protein in 14 of 17 globes, and vascular endothelial growth factor was expressed in the vitreal cells in five of five globes. CONCLUSIONS: We have defined a syndrome associated with vitreal glial cell aggregates and neovascular proliferation from the optic nerve or retina, which leads to neovascular glaucoma. The inflammation and secondary glaucoma resulting from this syndrome appear poorly responsive to conventional medical therapies. The exact etiology of COGS remains undetermined, but a systemic etiology is unlikely.

Advanced exudative retinopathy with neovascular glaucoma as the clinical presentation of diabetes mellitus and severe combined hyperlipidemia: a case report.

UNLABELLED: A 50-year-old man presented with bilateralprogressive visual loss for 5 months. Visual acuity was reduced to countingfingers in the right eye and light perception in the left. Although neovascularizations were detected in the angles of the eyes, neovascular glaucoma and rubeosis iridis were demonstrated only in the left. Fundus examination showed bilateral advanced exudative retinopathy in both eyes. Severe attenuated retinal arteries and enlarged cupping with disc pallor were observed in the left eye. Generalized eruptive xanthomas were found on the back and extremities. Extreme dyslipidemia (serum cholesterol 1311 mg/dl and triglycerides 6356 mg/dl) and diabetes mellitus (fasting plasma glucose 325 mg/dl and HbA1 c 12.1%) were first diagnosed. The serum lipid profiles and glucose levels were dramatically decreased within a month after treatment with subcutaneous insulin injections and oral hypolipidemic agents; notwithstanding, his vision was not significantly improved, even after treatment with intravitreal anti-VEGF injection, intravitreal steroid injection and panretinal photocoagulation. CONCLUSION: The principle causes of advanced exudative retinopathy are severe breakdown of the blood-retinal barrier due to diabetes mellitus and altered retinal pigment epithelium lipid metabolism. In ourpatient, central retinal vascular occlusion was also the suspected cause ofneovascular glaucoma.

[Neovascular glaucoma treatment in 2012: role of anti-VEGF agents]. / Traitement du glaucome néovasculaire en 2012 : apport des anti-VEGF.

Neovascular glaucoma is a serious pathology with a variety of causes. It results from the secretion by hypoxic retinal tissue of growth factors, including vascular endothelial growth factor (VEGF). Anterior segment involvement begins in the iris, followed by the development of a fibrovascular membrane in the angle, with resultant goniosynechiae. Treatment of the underlying disease consists most often of panretinal photocoagulation. As for the secondary sequelae, current treatment consists of intravitreal injection of anti-VEGF agents. The most utilized agent is bevacizumab or Avastin, off-label. Avastin is effective against neovascularization and ocular hypertension, especially in the early stages. It also represents an adjunct to filtering surgery. It appears to be very well tolerated.

Erythropoietin levels in aqueous humor of patients with glaucoma.

PURPOSE: To compare the aqueous concentration of erythropoietin (EPO) in eyes with primary open-angle (POAG), pseudoexfoliative (PXFG), and neovascular (NVG) glaucoma with age-matched eyes with cataracts, and to correlate its concentration with other factors including age, gender, intraocular pressure (IOP), type of glaucoma, and severity of glaucoma. METHODS: In this prospective non-randomized comparative study, a total of 26 eyes with cataracts (control group) and 92 glaucomatous eyes (POAG, 40 eyes; PXFG, 26 eyes; NVG, 26 eyes) were enrolled. Aqueous samples (0.1 to 0.2 ml) were obtained during phacoemulsification, trabeculectomy, phacotrabeculectomy, or Ahmed valve glaucoma implants. The aqueous concentration of EPO was measured using an enzyme-linked immunosorbent assay. RESULTS: The mean±SEM aqueous level of EPO was statistically significantly higher in eyes with glaucoma (56.7±9.3 mIU/ml) compared to the control group (0.8±0.51 mIU/ml; p<0.001). Eyes with NVG had the highest aqueous level of EPO. Aqueous EPO concentrations remained considerably elevated even in eyes with controlled IOP in all three types of glaucoma. Eyes with PXFG displayed the greatest change in aqueous EPO concentration proportionate to the IOP level. In simple regression analysis, IOP, mean deviation, and the type of glaucoma were the factors that had a statistically significantly positive correlation with the aqueous level of EPO (p=0.011 and <0.001, respectively). Only the type of glaucoma remained statistically significant in the multiple regression analysis (adjusted R(2)=0.278). CONCLUSIONS: Compared to the control group, the aqueous humor EPO concentration is increased in eyes with POAG, PXFG, and NVG, both with and without controlled IOP. The aqueous level of EPO was more proportionate to the level of IOP in eyes with PXFG compared to eyes with POAG and NVG.

Pars plana Ahmed implantation combined with 23-gauge vitrectomy for refractory neovascular glaucoma in diabetic retinopathy.

PURPOSE: To evaluate the efficacy and safety of a pars plana Ahmed valve implantation combined with 23-gauge sutureless vitrectomy in the treatment of patients with medically uncontrolled neovascular glaucoma (NVG) in proliferative diabetic retinopathy (PDR). METHODS: The authors retrospectively reviewed the records of 11 consecutive patients with refractory NVG in PDR who underwent a 23-gauge sutureless vitrectomy combined with pars plana placement of an Ahmed valve implant. Control of intraocular pressure (IOP), pre- and postoperative best-corrected visual acuity and the development of intra- and postoperative complications were evaluated during the follow-up. RESULTS: The mean follow-up was 12.2 months (range, 8 to 25 months). Mean preoperative IOP was 35.9 ± 6.3 mmHg and mean postoperative IOP at the last visit was 13.3 ± 3.2 mmHg. Control of IOP (8 to 18 mmHg) was achieved in all patients, but 91% (10 of 11 patients) needed antiglaucoma medication (mean number of medications, 1.2 ± 0.6). Postoperative visual acuity improved in 11 eyes, and the logarithmically to the minimum angle of resolution mean visual acuity in these eyes improved from 1.67 ± 0.61 to 0.96 ± 0.67. The complications that occurred were transient hypotony in one case, transitory hypertension in two cases, and postoperative vitreous hemorrhage which spontaneously cleared in two cases. CONCLUSIONS: We suggest the combination of 23-gauge pars plana vitrectomy and Ahmed valve implantation is safe and effective in PDR patients with refractory NVG.

Clinical outcomes and changes in aqueous vascular endothelial growth factor levels after intravitreal bevacizumab for iris neovascularization and neovascular glaucoma: a retrospective two-dose comparative study.

PURPOSE: To evaluate the clinical outcomes and biologic effects on the aqueous humor concentrations of vascular endothelial growth factor (VEGF) in patients with neovascular glaucoma (NVG) treated with intravitreal bevacizumab (IVB). METHODS: Twenty-nine consecutive patients (35 eyes) treated with 1.0- or 0.1-mg injections of IVB for NVG between January and December 2009 were enrolled in this retrospective, interventional pilot study. The visual prognosis and changes in intraocular pressure (IOP) were followed for >6 months after the initial injection. Aqueous humor samples were obtained at the initial IVB injection from all study eyes and 1 week after the first injection in eyes undergoing a second intervention to measure the VEGF concentration. RESULTS: The VEGF concentrations in the 35 eyes significantly correlated (r=0.535, P<0.001) with the pretreatment IOP. The mean reductions of the VEGF levels 1 week after IVB did not differ significantly between the 1.0- and 0.1-mg groups (P=0.738). Despite more repeated injections in the 0.1-mg group and additional medical or surgical interventions in both groups, both dosages inhibited the neovascular activity. The ability to control the IOP after IVB did not differ significantly between groups at 1 week (P=0.625) and 6 months (P>0.99). Visual improvements also did not differ significantly between groups during the 6-month follow-up (P=0.437). CONCLUSIONS: Aqueous humor levels of VEGF were significantly correlated with the IOP. Low-dose (0.1 mg) IVB was as effective as the currently used higher dose (1.0 mg) for treating NVG within at least 6 months after the initial injection.

[Results in neovascular glaucoma treatment]. / Rezultate terapeutice in glaucomul neovascular.

This report presents the results of a study on 34 patients with neovascular glaucoma. We analyse the difficulties and the results of the management of this severe form of glaucoma.

Intravitreal bevacizumab treatment for neovascular glaucoma: histopathological analysis of trabeculectomy specimens.

BACKGROUND: Neovascular glaucoma (NVG) is a serious complication for patients with proliferative diabetic retinopathy (PDR). Bevacizumab is a full-length humanized monoclonal antibody that binds all isoforms of vascular endothelial growth factor (VEGF). Recently, encouraging results regarding the off-label use of intravitreal bevacizumab (IVB) for the treatment of NVG have been reported. We evaluated the histology of bevacizumab-treated trabeculectomy specimens to clarify IVB's biological effects on angle neovascularization. METHODS: We retrospectively reviewed the charts of a consecutive series of 15 eyes of 13 patients who underwent trabeculectomy to treat NVG caused by PDR. In ten eyes of eight patients, 1.25 mg bevacizumab was injected intravitreally via the pars plana. Using light or electron microscopy, the surgically excised trabecular tissue was compared to that without IVB. RESULTS: Light microscopy revealed decreased edema, fibrin deposition, inflammation and vascular congestion in the trabecular meshwork in specimens with IVB compared to those without IVB. Electron microscopy revealed endothelial cell degeneration in the bevacizumab-treated specimens. CONCLUSIONS: The biological effects on angle neovascularization after IVB may involve reduced vascular permeability, decreased inflammatory reaction, loss of vascular function, and endothelial cell degeneration.

Rabbit rubeosis iridis induced by intravitreal latex-derived angiogenic fraction.

PURPOSE: To describe the presence of iris neovascularization in a rabbit-model of retinal neovascularization induced by the intravitreal injection of latex-derived angiogenic fraction microspheres (LAF). MATERIALS AND METHODS: Eight New Zealand rabbits received one intravitreal injection of PLGA (L-lactide-co-glycolide) microspheres with 50 ug of LAF in the right eye (Group A). Microspheres without the LAF (0.1 ml) were injected in controls (Group B; n = 8). Follow-up with clinical evaluation and iris fluorescein angiography was performed after 4 weeks when eyes were processed for light microscopy. RESULTS: All eyes from Group A showed significant vascular dilation, conjunctival hyperemia and neovascularization on the iris surface, after LAF injection. No vascular changes were observed in Group B. CONCLUSIONS: The intravitreal injection of microspheres containing the LAF can induce rubeosis iridis in rabbits and could be used as a simple experimental model for iris neovascularization.