Corneal Vessels Research Articles

Novel strategies for angioregression at the ocular surface

AbstractThe normal human cornea is avascular. This avascularity is actively maintained by expression of antiangiogenic and antilymphangiogenic factors. Corneal neovascularization (NV) can occur after numerous corneal diseases and leads to decreased visual acuity and poor prognosis in subsequent corneal transplantation since corneal immune privilege is lost. We recently demonstrated that bevacizumab eye drops significantly inhibit progressive corneal angiogenesis. In contrast, limited treatment options exist for mature corneal vessels, which — because of their pericyte‐covered vessel wall—do not depend on VEGF anymore. Here, we report on the short‐ and long‐term visual acuity changes and changes in vascularized corneal area after e.g. feeder vessel coagulation combined with topical bevacizumab application for the treatment of mature pathological corneal NV . These angioregressive therapies may not only improve corneal transparency but also “preconditions” such a cornea for future keratoplasty.

Lymphatic Vessel Memory Stimulated by Recurrent Inflammation

Inflammation stimulates new lymphatic vessel growth (inflammatory lymphangiogenesis). One key question is how recurrent inflammation, a common clinical condition, regulates lymphatic vessel remodeling. We show here that recurrent inflammation accelerated the development a functional lymphatic vessel network. This observation suggests a novel program of lymphangiogenesis and identifies a property of lymphatic vessel memory in response to recurrent inflammation. A brief episode of initial inflammation regressed lymphatic vessels, and a significant increase in CD11b(+) macrophages were associated with the development of lymphatic vessel memory. These vessels had major differences in the structure and the spatial distribution of specialized lymphatic vessel features. Surprisingly, we found that the lymphatic vessel memory response did not depend on the vascular endothelial growth factor C or A pathway, indicating that different molecular pathways regulate inflammatory lymphangiogenesis and lymphatic vessel memory. These findings uncover a priming mechanism to facilitate a rapid lymphatic vessel memory response: a potential important component of peripheral host defense.

Allograft survival enhancement using doxycycline in alkali‐burned mouse corneas

To explore the inhibitory effects of doxycycline on allograft rejection in alkali-burned cornea beds. The corneas of BALB/c mice were injured using a 1 mol/l NaOH solution. Following the injury, the corneas from C57BL/6 mice were transplanted into the eyes of BALB/c mice after being randomized into three groups: allogeneic corneal transplantation (group A), topical use of doxycycline after allogeneic corneal transplantation (group B) and syngeneic corneal transplantation (group C). Corneal angiogenesis was examined using whole-mount immunofluorescence, and corneal inflammation was evaluated using inflammation index scoring. The immune rejection of the grafts was examined using a slit lamp. In addition, the expression of vascular endothelial growth factor A and interleukin-1β in the transplanted corneas was examined using a real-time polymerase chain reaction, immunohistochemistry and an enzyme-linked immunosorbent assay. The outgrowth of the corneal blood vessels in the group A mice was faster than that in the group B and group C mice. The inflammation index levels were highest in the group A mice, intermediate in the group B mice and lowest in the group C mice. Vascular endothelial growth factor and the interleukin-1β protein and mRNA levels decreased dramatically in the group B mice compared with the group A mice (all p-values < 0.01). In addition, the mean survival time in the group B mice (27.00 ± 2.00 days) was significantly longer than that in the group A mice (11.67 ± 1.51 days; p < 0.05). Doxycycline may have had a significant role in preventing corneal angiogenesis and inflammation in alkali-burned corneal beds, which resulted in higher allograft survival rates.

Novel anti(lymph)angiogenic treatment strategies for corneal and ocular surface diseases

The cornea is one of the few tissues which actively maintain an avascular state, i.e. the absence of blood and lymphatic vessels (corneal [lymph]angiogenic privilege). Nonetheless do several diseases interfere with this privilege and cause pathologic corneal hem- and lymphangiogenesis. The ingrowths of pathologic blood and lymphatic vessels into the cornea not only reduce transparency and thereby visual acuity up to blindness, but also significantly increases the rate of graft rejections after subsequent corneal transplantation. Therefore great interest exists in new strategies to target pathologic corneal (lymph)angiogenesis to promote graft survival. This review gives an overview on the vascular anatomy of the normal ocular surface, on the molecular mechanisms contributing to the corneal (lymph)angiogenic privilege and on the cellular and molecular mechanisms occurring during pathological neovascularization of the cornea. In addition we summarize the current preclinical and clinical evidence for three novel treatment strategies against ocular surface diseases based on targeting pathologic (lymph)angiogenesis: (a) modulation of the immune responses after (corneal) transplantation by targeting pathologic (lymph)angiogenesis prior to and after transplantation, (b) novel concepts against metastasis and recurrence of ocular surface tumors such as malignant melanoma of the conjunctiva by anti(lymph)angiogenic therapy and (c) new ideas on how to target ocular surface inflammatory diseases such as dry eye by targeting conjunctival and corneal lymphatic vessels. Based on compelling preclinical evidence and early data from clinical trials the novel therapeutic concepts of promoting graft survival, inhibiting tumor metastasis and dampening ocular surface inflammation and dry eye disease by targeting (lymph)angiogenesis are on their way to translation into the clinic.

Safety and Efficacy of the Multitargeted Receptor Kinase Inhibitor Pazopanib in the Treatment of Corneal Neovascularization

To evaluate the safety and efficacy of topical pazopanib in the treatment of corneal neovascularization (CNV). Twenty eyes of 20 patients with stable CNV were enrolled in a prospective, open label, noncomparative study and treated with topical pazopanib 0.5% for 3 weeks, and followed for 12 weeks. The primary endpoint was to determine the tolerability and safety of topical pazopanib in the treatment of CNV defined by the occurrence of ocular and systemic adverse events during the study. The secondary endpoint was to evaluate the effect of topical pazopanib on the reduction of (1) neovascular area (NA), defined as the area of the corneal vessels themselves, (2) invasion area (IA), defined as the fraction of the total cornea into which the vessels extend, (3) vessel length (VL), defined as the mean measurement of the extent of vessels from end to end, and (4) vessel caliber (VC), defined as the mean diameter of the corneal vessels. There were no severe adverse events following the use of topical pazopanib. Compared with the baseline visit, NA and VL showed a statistically significant decrease at week 3 (P = 0.02 and 0.01, respectively); and NA, IA, and VL statistically significantly decreased at week 12 (P = 0.03, 0.04, and <0.01, respectively). Visual acuity maintained without changes after the 12 week follow-up. This preliminary study suggests that topical treatment with pazopanib 0.5% is safe, well tolerated, and may have a role as an alternative for the treatment of CNV (ClinicalTrials.gov number, NCT01257750).

Evaluation of Corneal Vessels

Corneal new vessels can result in significant loss of vision as well as reduce graft survival. Recently, newer treatment modalities have been introduced. However, attempts to meet the challenge of evaluating corneal vessels by quantification are evolving.In vivoevaluations range from computer-aided analysis of colour images to determination of area, diameter and tortuousity of blood vessels on indocyanine green angiography images. Attempts at developing a fully automated process of evaluation and quantification are hampered by the anatomical variations of limbus, random nature of blood vessels and multiple levels of involvement of the corneal stroma. Currently, semi-automated methods require manually fixing the limbus prior to quantification of vessels. Using indocyanine green angiography, the full extent of corneal vessels even in the presence of scarring can be determined. With the evolution of new techniques, it is hoped that a robust corneal vessel quantifying tool will be described in the near future that will aid the effectiveness of treatment strategies.

Short-Term Topical Bevacizumab in the Treatment of Stable Corneal Neovascularization

To evaluate the safety and efficacy of topical bevacizumab in the treatment of corneal neovascularization. Prospective, nonrandomized, interventional case series. setting: Institutional, multicenter clinical trial. study population: Twenty eyes from 20 patients with stable corneal neovascularization. intervention procedures: Patients were treated with topical 1.0% bevacizumab for 3 weeks and were monitored for a total of 24 weeks. main outcome measures: Primary outcome measures included: neovascular area, defined as the area of the corneal vessels themselves; vessel caliber, defined as the mean corneal vessel diameter; and invasion area, defined as the fraction of the total cornea into which the vessels extended. The occurrence of ocular and systemic adverse events was monitored closely. As compared with the baseline visit, patients exhibited a statistically significant improvement in neovascular area by week 6 (P = .007) and in vessel caliber by week 12 (P = .006). At the final visit, neovascular area, vessel caliber, and invasion area were reduced by 47.5%, 36.2%, and 20%, respectively. The decreases in neovascular area and vessel caliber were statistically significant (P < .001 and P = .003, respectively); however, the reduction in invasion area did not reach statistical significance (P = .06). There were no significant changes in the secondary outcomes, and there were no adverse events. Short-term topical bevacizumab treatment reduced the extent of stable corneal neovascularization as measured by neovascular area and vessel caliber with no associated adverse events. Interestingly, the degree of treatment efficacy was inversely proportional to the baseline invasion area.

Effects of subconjunctival bevacizumab on corneal neovascularization: results of a prospective study

AbstractPurpose To evaluate the effect of subconjunctival bevacizumab injections in patients with corneal neovascularization resulting from different ocular surface disorders.Methods Prospective case series. Fourteen eyes of 13 patients with corneal neovascularization caused by different ocular surface disorders, such as healed corneal ulcers, long‐standing chronic inflammatory diseases and corneal ischaemia secondary to burn were included. All eyes received a single subconjunctival injection of 2.5 mg (0.1 ml) bevacizumab. Morphological changes in neovascularization were evaluated during 3 months using slit‐lamp biomicroscopy, corneal digital photography, and computed‐assisted semi‐automatic analysis of corneal neovascularization area.Results Recession of corneal vessels was observed in all eyes at 1 week post‐injection. The surface of the neovascular tree continued to decrease noticeably for one month and then increased again for the remainder of the follow‐up period. The corneal neovascularization area amounted to 12.14± 4.38% of the corneal surface pre‐injection, compared with 9.10± 3.16% post‐injection (p=0.02), reflecting a mean decrease in corneal neovascularization of 25 %. No local or systemic adverse events possibly related to subconjunctival bevacizumab injection were observed.Conclusion Short‐term results suggest that subconjunctival bevacizumab can be used safely and effectively for corneal neovascularization resulting from different ocular surface disorders, providing an additional strategy to improve success of corneal grafts.

Angioregressive Pretreatment of Mature Corneal Blood Vessels Before Keratoplasty

To evaluate the efficacy and safety of combined feeder vessel coagulation and topical antiangiogenic therapy using bevacizumab in the treatment of mature corneal blood vessels. Sixteen eyes of 16 patients with mature corneal neovascularization (NV) due to different underlying corneal diseases underwent fine-needle feeder vessel coagulation by diathermy and were treated postoperatively for up to 4 weeks with topical bevacizumab eye drops (containing 5 mg/mL bevacizumab) 5 times a day. Nine patients received an additional subconjunctival bevacizumab injection at the time of cautery. The mean duration of follow-up was 276 ± 147.3 days (range, 29-464 days). Regression of the feeder vessel was observed in 14 eyes. The vascularized area was reduced significantly (P < 0.05). Combined subconjunctival and eye drop antivascular endothelial growth factor treatment was significantly more effective in reducing the vascularized area compared with antivascular endothelial growth factor eye drop therapy alone (P < 0.05). Five patients (5 eyes) needed a second treatment. Thirteen patients (13 eyes) receiving topical bevacizumab treatment combined with feeder vessel coagulation showed stable visual acuity. Two patients had improved visual acuity. One patient had enlarged area of lipid keratopathy despite successful treatment of corneal NV and thus decreased visual acuity. Overall, there was a nonsignificant improvement of best-corrected visual acuity (P > 0.05). In this pilot study, fine-needle feeder vessel coagulation combined with topical bevacizumab application for treatment of mature corneal NV seemed to be a well-tolerated new treatment option to regress corneal NV. This may not only improve corneal transparency but also "preconditions" such a cornea for future keratoplasty.

Effects of Subconjunctival Bevacizumab on Corneal Neovascularization

To evaluate the effect of subconjunctival bevacizumab injections in patients with corneal neovascularization resulting from different ocular surface disorders. Prospective case series. Twelve eyes of 11 patients with corneal neovascularization caused by different ocular surface disorders, such as healed corneal ulcers, long-standing chronic inflammatory diseases, and corneal ischemia secondary to burn, were included. All eyes received a single subconjunctival injection of 2.5 mg (0.1 mL) of bevacizumab. Morphological changes in neovascularization were evaluated during 3 months using slit-lamp biomicroscopy, corneal digital photography, and computer-assisted semiautomatic analysis of corneal neovascularization area. Recession of corneal vessels was observed in all eyes at 1 week postinjection. The surface of the neovascular tree continued to decrease noticeably for 1 month and then increased again for the remainder of the follow-up period. The corneal neovascularization area amounted to 11.25 ± 4.49% of the corneal surface preinjection, compared with 8.44 ± 3.37% postinjection (P = 0.02), reflecting a mean decrease in corneal neovascularization of 25%. No local or systemic adverse events possibly related to subconjunctival bevacizumab injection were observed. Short-term results suggest that subconjunctival bevacizumab can be used safely and effectively for corneal neovascularization resulting from different ocular surface disorders, providing an additional strategy to improve success of corneal grafts.

B-FGF Induces Corneal Blood and Lymphatic Vessel Growth in a Spatially Distinct Pattern

To study the spatial variances in ligand expression and angiogenic effect in response to the inflammatory response induced by basic fibroblast growth factor (b-FGF). b-FGF micropellets (80 ng) were implanted in the temporal side of the cornea of Balb/c mice. On days 1, 3, and 7, blood (heme-) and lymphangiogenesis were observed by immunofluorescence staining of corneal flat mounts with LYVE-1 and CD31 to identify lymphatic and blood vessels, respectively. A second group of corneas were harvested for quantitative real-time polymerase chain reaction. Each cornea was divided into 2 different areas: (1) pre-pellet area and (2) opposite-pellet area. Expression of vascular endothelial growth factor (VEGF) ligands was evaluated using real-time polymerase chain reaction in each respective zone. Blood vessels grew into the cornea from the pre-pellet area, whereas corneal lymphatic vessels grew from the opposite-pellet area toward the center of the cornea. VEGF-A was upregulated in the pre-pellet, whereas VEGF-D expression was mostly observed in the opposite-pellet area. VEGF-C level increased simultaneously in both areas. A single inducing factor, that is, b-FGF, may simultaneously provoke hemangiogenesis and lymphangiogenesis in different locations of the cornea through differential expression of VEGF ligands. This distinctive spatial pattern should be considered while evaluating the corneal predilection for inflammation beyond that which is directly visible by slit lamp examination.

Bilateral Progressive Idiopathic Annular Lipid Keratopathy

Purpose. To report two unusual cases of idiopathic lipid keratopathy with symmetrical bilateral annular corneal lipid infiltration and describe confocal microscopy findings. Methods. Case reports. Results. We report two patients with bilateral peripheral deep stromal lipid deposits beginning in an arcuate pattern and progressing to a complete annular shape. Cholesterol crystals were observed in the paracentral area in both cases with characteristic crystalline-like structures in the confocal microscopy. Deep thin corneal blood vessels were observed in one patient, but no cause for then was established, despite decades of followup. This patient had an idiopathic limbitis as well, occurring in episodes. No previous ocular trauma, systemic disease or family history was reported for both cases. Conclusion. These two cases of idiopathic annular lipid keratopathy were observed for more than a decade with documented slow and insidious progression of the infiltrates, in spite of the use of topical steroids in one case. In the majority of other reported cases, a penetrating keratoplasty was made necessary. Differently, we showed that the visual acuity can remain quite good for years with very slow deterioration.

Forkhead box transcription factor FoxC1 preserves corneal transparency by regulating vascular growth

Normal vision requires the precise control of vascular growth to maintain corneal transparency. Here we provide evidence for a unique mechanism by which the Forkhead box transcription factor FoxC1 regulates corneal vascular development. Murine Foxc1 is essential for development of the ocular anterior segment, and in humans, mutations have been identified in Axenfeld-Rieger syndrome, a disorder characterized by anterior segment dysgenesis. We show that FOXC1 mutations also lead to corneal angiogenesis, and that mice homozygous for either a global (Foxc1(-/-)) or neural crest (NC)-specific (NC-Foxc1(-/-)) null mutation display excessive growth of corneal blood and lymphatic vessels. This is associated with disorganization of the extracellular matrix and increased expression of multiple matrix metalloproteinases. Heterozygous mutants (Foxc1(+/-) and NC-Foxc1(+/-)) exhibit milder phenotypes, such as disrupted limbal vasculature. Moreover, environmental exposure to corneal injury significantly increases growth of both blood and lymphatic vessels in both Foxc1(+/-) and NC-Foxc1(+/-) mice compared with controls. Notably, this amplification of the angiogenic response is abolished by inhibition of VEGF receptor 2. Collectively, these findings identify a role for FoxC1 in inhibiting corneal angiogenesis, thereby maintaining corneal transparency by regulating VEGF signaling.

The association between corneal neovascularization and visual acuity: a systematic review

Corneal neovascularization (CNV) is thought to negatively influence visual acuity. New therapeutic options that offer a differentiated influence on the ingrowths or regression of either corneal blood or lymphatic vessels force us to re-evaluate the association between CNV and visual acuity. A systematic review was conducted. Electronic databases were searched up to August 2009. Given the heterogeneity in study populations, interventions and measures of association, we were unable to undertake meta-analysis. The association between CNV and visual acuity was reported descriptively for each study. Eleven studies using either vascular endothelial growth factor inhibitor treatments (i.e. bevacizumab, Avastin(®) ; Hoffmann-La Roche AG, Basel, Switzerland) or an antiangiogenic treatment based on IRS-1 modulation [Gene-Signal (GS) 101, Aganirsen(®) ; GeneSignal, Evry (Paris), France] in a total of 131 patients (142 eyes) with corneal neovascularization were included. Ten of the eleven studies reported evidence of a statistically significant reduction in neovascularization following treatment. However, only four studies reported a statistically significant improvement in visual acuity following therapy. We found no studies that assessed the patient-level association between the change in neovascularization and visual acuity. This systematic review found that there is currently weak evidence to support the hypothesis that in patients with pathological neovascularization, a treatment-related reduction in neovascularization is associated with an increase in visual acuity. There is a need for future appropriately designed studies.

Identification of novel neutralizing single‐chain antibodies against vascular endothelial growth factor receptor 2

Human vascular endothelial growth factor (VEGF) and its receptor (VEGFR-2/kinase domain receptor [KDR]) play a crucial role in angiogenesis, which makes the VEGFR-2 signaling pathway a major target for therapeutic applications. In this study, a single-chain antibody phage display library was constructed from spleen cells of mice immunized with recombinant human soluble extracellular VEGFR-2/KDR consisting of all seven extracellular domains (sKDR D1-7) to obtain antibodies that block VEGF binding to VEGFR-2. Two specific single-chain antibodies (KDR1.3 and KDR2.6) that recognized human VEGFR-2 were selected; diversity analysis of the clones was performed by BstNI fingerprinting and nucleotide sequencing. The single-chain variable fragments (scFvs) were expressed in soluble form and specificity of interactions between affinity purified scFvs and VEGFR-2 was confirmed by ELISA. Binding of the recombinant antibodies for VEGFR-2 receptors was investigated by surface plasmon resonance spectroscopy. In vitro cell culture assays showed that KDR1.3 and KDR2.6 scFvs significantly suppressed the mitogenic response of human umbilical vein endothelial cells to recombinant human VEGF(165) in a dose-dependent manner, and reduced VEGF-dependent cell proliferation by 60% and 40%, respectively. In vivo analysis of these recombinant antibodies in a rat cornea angiogenesis model revealed that both antibodies suppressed the development of new corneal vessels (p < 0.05). Overall, in vitro and in vivo results disclose strong interactions of KDR1.3 and KDR2.6 scFvs with VEGFR-2. These findings indicate that KDR1.3 and KDR2.6 scFvs are promising antiangiogenic therapeutic agents.

Inflammatory Corneal Neovascularization: Etiopathogenesis

There is a delicate balance between pro-angiogenic stimuli and anti-angiogenic stimuli in the normal cornea. This balance allows the cornea to normally exist in a relatively avascular state, which is needed for optical clarity and vision. However, in the setting of inflammation, this balance may be shifted in favor of neovascularization.This paper reviews the literature on corneal inflammatory neovascularization beginning with the pro-angiogenic factors, such as Vascular Endothelial Growth Factor and Fibroblast Growth Factor, which help to facilitate the development of new corneal vessels. Subsequently the anti-angiogenic factors and their role in preventing neovascularization in the normal cornea are reviewed. Finally, a review of several etiologies of inflammatory neovascularization is presented with attention to the processes that allow the pro-angiogenic stimuli to overwhelm the anti-angiogenic factors.

Effects of Trehalose on VEGF-Stimulated Angiogenesis and Myofibroblast Proliferation: Implications for Glaucoma Filtration Surgery

To investigate whether trehalose inhibits VEGF-stimulated or inflammatory angiogenesis and the proliferation of myofibroblasts. Normal human dermal fibroblasts and human umbilical vein endothelial cells (HUVECs)were cocultured in trehalose-containing medium (2.5/5.0/7.5/10.0%) with or without VEGF (10 ng/mL). After 11 days, the area, length, joint, and path of neovascularization were evaluated. The effect of topical trehalose on corneal neovascularization was examined in vivo by treating Balb/c mice with alkali burn-induced corneal neovascularization. After 14 days of trehalose treatment, corneal vessels were visualized in flatmounts. The expressions of VEGFR2, phospho-VEGFR2, and vimentin were observed. Then a separate coculture model of the myofibroblasts and HUVECs was used to observe the morphologic changes of the myofibroblasts by trehalose. Furthermore, myofibroblasts were cultured with trehalose to examine the cytokeratin and E-cadherin expressions. In the in vitro models, there was a significant trehalose dose-dependent inhibition of neovascularization. In the in vivo alkali burn models, corneal neovascularization was significantly inhibited by treatments using ≥ 2.5% trehalose eyedrops. The expressions of VEGFR2, phospho-VEGFR2, and vimentin were downregulated by trehalose. When trehalose was added to the medium, the myofibroblasts were transformed into epithelial cell-like cells. The transformed myofibroblasts expressed cytokeratin but not E-cadherin. Trehalose prevents angiogenesis by partially downregulating VEGFR2 expression. In addition, trehalose inhibits the proliferation of myofibroblasts partially by inducing mesenchymal-epithelial transition. These findings suggest that trehalose has potential for use as a new agent that can control angiogenesis and fibrosis and potential for use in glaucoma surgery.

Late-onset Fabry disease associated with angiokeratoma of Fordyce and multiple cherry angiomas

Fabry disease (FD) is a lysosomal storage disorder. The prevalence and clinical spectrum is higher than previously thought. The average time between onset of symptoms and diagnosis is 10 years. Early identification of patients is essential to institute enzyme therapy and reduce morbidity. We report the case of a 76-year-old man, who presented with loss of consciousness following exertional chest pain. He was found to have tortuous corneal vessels, > 100 cherry angiomas on his trunk, and angiokeratomas on his scrotum. The latter were indistinguishable from angiokeratoma of Fordyce, a diagnosis reported in 15% of men over the age of 50 years, and generally ignored by them. The patient's α-galactosidase levels were low, and a mutation in exon 5 of the GLA gene was identified on DNA analysis, confirming the diagnosis of FD. This case highlights the importance of considering a diagnosis of FD in all male patients with angiokeratoma. It also raises the question of whether the presence of multiple cherry angiomas in patients with cardiac disease should raise the possible diagnosis of FD.

Isoliquiritigenin from licorice root suppressed neovascularisation in experimental ocular angiogenesis models

AimTo explore the antiangiogenic property of isoliquiritigenin (ISL) on in vivo and in vitro models.DesignLaboratory investigation.MethodsThe effect of ISL on angiogenesis development was investigated using ex ovo chick chorioallantoic membrane...

Photodynamic Therapy With Verteporfin Combined With Subconjunctival Injection of Bevacizumab for Corneal Neovascularization

To investigate the efficacy of combined photodynamic therapy with verteporfin and subconjunctival injection of bevacizumab for the treatment of patients with corneal neovascularization. Twelve eyes of 12 patients with stable corneal neovascularization who were refractory to conventional treatment were treated with photodynamic therapy with verteporfin (6 mg/m) and subconjunctival injection of bevacizumab (2.5 mg/0.1 mL). Anterior segment photography was performed before and after treatment. Best-corrected visual acuity, cumulative length of corneal blood vessels, and area of corneal neovascularization were measured. From 1 week to 1 month after treatment, all eyes showed a notable decrease in corneal neovascularization and evidence of vascular thrombosis. At the 6-month and 1-year follow-ups, complete vascular occlusion was achieved in 8 eyes (66.7%) and partial occlusion was achieved in 3 eyes (25.0%). One eye (8.3%) showed revascularization after temporary occlusion. No ocular complications or systemic events developed. Photodynamic therapy with verteporfin combined with subconjunctival injection of bevacizumab seems to be effective for the treatment of corneal neovascularization.