Search

Microbiota promotes or inhibits the pathogenesis of a range of immune-mediated disorders. Although recent studies have elucidated the role of gut microbiota in ocular disease, the effect of ocular microbiota remains unclear. Herein, we explored the role of ocular commensal bacteria in non-infectious corneal inflammation and angiogenesis in a mouse model of suture-induced corneal neovascularization. Results revealed that the ocular surface harbored a microbial community consisting mainly of Actinobacteria, Firmicutes and Proteobacteria. Elimination of the ocular commensal bacteria by oral broad-spectrum antibiotics or topical fluoroquinolone significantly suppressed corneal inflammation and neovascularization. Disease amelioration was associated with reduced numbers of CD11b + Ly6C + and CD11b + Ly6G + myeloid cells, not Foxp3 + regulatory T cells, in the spleen, blood, and draining lymph nodes. Therapeutic concentrations of fluoroquinolone, however, did not directly affect immune cells or vascular endothelial cells. In addition, data from a clinical study showed that antibiotic treatment in combination with corticosteroids, as compared with corticosteroid monotherapy, induced faster remission of corneal inflammation and new vessels in pediatric patients with non-infectious marginal keratitis. Altogether, our findings demonstrate a pathogenic role of ocular microbiota in non-infectious inflammatory disorders leading to sight-threatening corneal neovascularization, and suggest a therapeutic potential of targeting commensal microbes in treating ocular inflammation., (© 2022. The Author(s), under exclusive licence to Society for Mucosal Immunology.)

Objective: This case report aims to explore the use of scleral lenses for the treatment of ocular and visual complications in an adult patient presenting with post-LASIK (Laser-Assisted in situ Keratomileusis) ectasia in both eyes with cross-linking in the right eye and intrastromal corneal ring segments (ICRS; Intacs, Addition Technology, Fremont, CA) in the left eye., Methods: Following a comprehensive eye exam and specific testing for contact lens fitting, scleral lenses were fitted with success in both eyes and dispensed. Due to progressive fibrosis and neovascularization of the inferior ICRS in the left eye, the inferior ICRS was removed and scleral lenses were refit with success., Results: Prescribed scleral lenses helped the patient achieve optimal visual correction (20/20) as well as ocular protection of the cornea., Conclusion: Post-LASIK ectasia is a common finding among contact lens specialists today. When ICRS surgery is involved, the fitting of contact lenses may become more challenging. Scleral lenses offer a unique way of addressing many issues raised in this case report including corneal neovascularization and ectasia. This lens modality may be considered for any other case involving irregular corneal curvature following surgery resulting in reduced visual acuity., (Copyright © 2015 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

Objective: Eye drops of aganirsen, an antisense oligonucleotide preventing insulin receptor substrate-1 expression, inhibited corneal neovascularization in a previous dose-finding phase II study. We aimed to confirm these results in a phase III study and investigated a potential clinical benefit on visual acuity (VA), quality of life (QoL), and need for transplantation., Design: Multicenter, double-masked, randomized, placebo-controlled phase III study., Participants: Analysis of 69 patients with keratitis-related progressive corneal neovascularization randomized to aganirsen (34 patients) or placebo (35 patients). Patients applied aganirsen eye drops (86 μg/day/eye) or placebo twice daily for 90 days and were followed up to day 180., Main Outcome Measures: The primary end point was VA. Secondary end points included area of pathologic corneal neovascularization, need for transplantation, risk of graft rejection, and QoL., Results: Although no significant differences in VA scores between groups were observed, aganirsen significantly reduced the relative corneal neovascularization area after 90 days by 26.20% (P = 0.014). This improvement persisted after 180 days (26.67%, P = 0.012). Aganirsen tended to lower the transplantation need in the intent-to-treat (ITT) population at day 180 (P = 0.087). In patients with viral keratitis and central neovascularization, a significant reduction in transplantation need was achieved (P = 0.048). No significant differences between groups were observed in the risk of graft rejection. However, aganirsen tended to decrease this risk in patients with traumatic/viral keratitis (P = 0.162) at day 90. The QoL analyses revealed a significant improvement with aganirsen in composite and near activity subscores (P = 0.039 and 0.026, respectively) at day 90 in the per protocol population. Ocular and treatment-related treatment-emergent adverse events (TEAEs) were reported in a lower percentage with aganirsen compared with placebo. Only 3 serious TEAEs (2 with aganirsen and 1 with placebo) were considered treatment-related., Conclusions: This first phase III study on a topical inhibitor of corneal angiogenesis showed that aganirsen eye drops significantly inhibited corneal neovascularization in patients with keratitis. The need for transplantation was significantly reduced in patients with viral keratitis and central neovascularization. Topical application of aganirsen was safe and well tolerated., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the effects of resveratrol and bevacizumab on experimental corneal neovascularization., Method: A corneal alkali burn was performed in 62 eyes of 31 male white Vienna rabbits. Resveratrol (group 1), dimethyl sulfoxide (group 2), bevacizumab (group 3) and 0.9% NaCl (group 4) were administered to both eyes of the rabbits by subconjunctival injection for 7 days. Corneal photos were taken at 15 days after alkali injury. Inflammatory index scores and neovascularization areas were calculated., Results: In bevacizumab group both inflammatory index scores and the calculation of the corneal neovascularization area was significantly less than the groups., Conclusion: The subconjunctival administration of bevacizumab inhibits corneal neovascularization effectively in the rabbit corneal alkali burn model. No effect of resveratrol to the corneal neovascularization on experimental model of the corneal alkali burn was seen at the doses of usage., (Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.)

Purpose: To evaluate the use of subconjunctival bevacizumab on corneal neovascularization in an experimental rabbit model for its effect on vessel extension, inflammation, and corneal epithelialization., Methods: In this prospective, randomized, blinded, experimental study, 20 rabbits were submitted to a chemical trauma with sodium hydroxide and subsequently divided into two groups. The experimental group received a subconjunctival injection of bevacizumab (0.15 m; 3.75 mg), and the control group received an injection of 0.15 ml saline solution. After 14 days, two blinded digital photograph analyses were conducted to evaluate the inflammation/diameter of the vessels according to pre-established criteria. A histopathological analysis of the cornea evaluated the state of the epithelium and the number of polymorphonuclear cells., Results: A concordance analysis using Kappa's statistic showed a satisfactory level of agreement between the two blinded digital photography analyses. The neovascular vessel length was greater in the control group (p<0.01) than in the study group. However, the histopathological examination revealed no statistically significant differences between the groups in terms of the state of the epithelium and the number of polymorphonuclear cells., Conclusions: Subconjunctival bevacizumab inhibited neovascularization in the rabbit cornea. However, this drug was not effective at reducing inflammation. The drug did not induce persistent corneal epithelial defects.

Angiogenesis has become a major issue in oncology. Different in vivo angiogenesis assays have been developed in order to better understand fundamental aspects of vascular development or to investigate the effect of therapeutic molecules on blood vessel growth. In this article, we will briefly review the main in vivo angiogenesis assays relevant to oncology and discuss their advantages and disadvantages.

Ocular neovascularization often results in vision impairment. Frequently vascular endothelial cell growth factors (VEGFs) are mainly responsible for the pathological neovascularization as in the case in neovascularization induced by CpG oligodeoxynucleotides and herpes simplex virus infection in this report. siRNAs targeting either VEGFA, VEGFR1, VEGFR2, or a mix of the three were shown to significantly inhibit neovascularization induced by CpG when given locally or systemically. The efficacy of systemic administration was facilitated by the use of a polymer delivery vehicle. Additional experiments showed a significant inhibitory effect of the siRNAs mix when given either locally or systemically in vehicle against herpes simplex virus-induced angiogenesis as well as against lesions of stromal keratitis. These results indicate that the use of VEGF pathway-specific siRNAs represents a useful therapy against neovascularization-related eye diseases.

Purpose: To review the clinical characteristics and visual outcomes of patients with bilateral herpetic keratitis., Design: Retrospective, noncomparative, observational case series., Patients and Methods: A retrospective review of medical records of 544 patients with herpes simplex virus (HSV) eye disease treated between January 1996 and September 2001 was performed at the Department of Ophthalmology, University of Minnesota. Seven patients (1.3%) with bilateral herpetic keratoconjunctivitis were identified., Results: In these seven patients, the age at the initial onset of corneal disease ranged from 7 weeks to 46 years, with a median of 18 years and a mean of 19.3 years. Five patients had systemic atopy, and two patients had severe ocular rosacea. Systemic immune disorders were noted in two patients. Recurrent blepharoconjunctivitis was noted in 8 eyes (57%), epithelial keratitis in 12 eyes (85.7%), stromal keratitis in 9 eyes (64.3%), necrotizing stromal keratitis in 5 eyes (35.7%), and progressive endotheliitis in 2 eyes (14.2%). Corneal complications included opacification, neovascularization, and corneal thinning or perforation. Penetrating keratoplasty was performed in 1 eye, in which endophthalmitis subsequently developed and which required enucleation. Four patients with continued use of oral antiviral prophylaxis (acyclovir 400 mg twice daily) since September 1999 showed significant decreases in recurrence. The average remission in these four patients was 1.7 years. The visual acuity at the last follow-up was 20/40 or worse in 6 eyes (42.8%)., Conclusions: In contrast to unilateral HSV keratitis, our patients with bilateral herpetic corneal infections had underlying atopy or immune deviations and evinced more protracted clinical courses. Long-term prophylactic antiviral treatment has reduced the incidence of recurrence in this group of patients.

Chronic exposure of the South American opossum, Monodelphis domestica, to ultraviolet radiation (UVR) induced 154 primary tumours of the cornea in 152 eyes. Tumours developed gradually; frank neoplasia was preceded by non-neoplastic proliferation of corneal stromal fibroblasts (keratocytes) and extensive neovascularization. Histologically, the majority of tumours (134 of 154) appeared to be fibrosarcomas arising from keratocytes, but about 12 per cent of the tumours (18 of 154) had a highly vascular appearance, suggesting haemangiosarcoma. In two eyes, squamous cell carcinomas overlay mesenchymal tumours. Ultrastructural features of UVR-induced corneal tumours were consistent with tumours, and cultured skin fibroblasts expressed high content of messenger RNA for the intermediate filament vimentin; no cytokeratin messenger RNA was detected in these cells and cell lines. Based upon their light microscopic, ultrastructural, and intermediate filament biosynthetic characteristics, the majority of UVR-induced corneal tumours in M. domestica appeared to be fibrosarcomas. Haemangiosarcomas constituted a smaller proportion of the tumours, and squamous cell carcinomas were very rare.

The authors treated corneal neovascularization in 25 eyes of 23 patients with corneal laser photocoagulation using 577 nm yellow light. Four groups of patients were treated: patients with corneal neovascularization and active graft rejection (group 1); patients with neovascularization before penetrating keratoplasty (PK) (group 2); lipid keratopathy patients with opacification and/or focal edema threatening the visual axis (group 3); and patients with extensive corneal neovascularization, who were not candidates for PK (group 4). Area of neovascularization and clinical outcome were monitored. After corneal laser photocoagulation, there was a statistically significant reduction in the neovascularized area in group 1 from 32% of corneal area to 10%, and in group 3 from 46% to 27%. All five patients in group 1 had resolution of their graft rejection. In group 3, there was a reduction in the area of corneal opacification from 59% of corneal area to 52%. This difference was not statistically significant. Seven of nine patients in group 3 had stabilization or improvement in their vision over a mean of 9.3 months follow-up. There was no significant change in neovascularized area in groups 2 and 4. In group 2, no rejection reactions occurred over a mean of 5.6 months follow-up after PK. In group 4, corneal laser photocoagulation was disappointing.

Deep corneal neovascularization is a recently described complication of contact lens wear. Visual loss associated with deep corneal neovascularization has been associated with stromal lipid leakage. Deep intracorneal hemorrhage is rare and has been documented infrequently with the use of contact lenses. The authors present five cases of deep stromal hemorrhage associated with contact lens-related deep corneal neovascularization. These patients had no other discernible cause for their vascularization and subsequent hemorrhage. One patient required a penetrating keratoplasty for visual rehabilitation. Contact lenses of all types may cause neovascularization. The deep stromal neovascularization develops insidiously and may progress in the absence of acute symptoms. The presence of deep stromal neovascularization must be watched carefully and managed as a potentially vision-threatening complication of contact lens use.