Long-Term Benefits of Tear Exchangeable Limbal-Rigid Contact Lens Wear Therapy in Stevens-Johnson Syndrome Cases.

OBJECTIVES: To evaluate the long-term benefits of tear-exchangeable, limbal-rigid contact lens (CL) wear therapy in patients with Stevens-Johnson syndrome (SJS)-associated ocular sequelae. METHODS: This retrospective study evaluated 50 eyes of 41 SJS patients (15 men and 26 women) who underwent limbal-rigid CL wear therapy for more than 2 years post fitting. Ocular sequelae (i.e., conjunctival hyperemia, corneal neovascularization, and upper tarsus scarring) before fitting and at 3 months, 6 months, 12 months, and annually after initiating CL wear therapy were evaluated and then graded on a severity score (range: 0-3, maximum score: 3). Moreover, visual acuity (VA) at immediately post initiating CL wear therapy was evaluated. RESULTS: The mean follow-up period was 4.3±1.1 years. Compared with before fitting, the mean conjunctival hyperemia score improved from 1.14 to 0.86 at 3 months of CL wear therapy ( P <0.01) and was maintained thereafter; the mean corneal neovascularization score improved from 2.10 to 1.98 at 3 months of CL wear therapy, with no deterioration of the score observed in all cases at the final follow-up examination, and mean VA (log of minimum angle of resolution) improved from 1.60 to 1.04 at immediately post initiating CL wear therapy ( P <0.01). CONCLUSIONS: Limbal-rigid CL wear therapy can provide long-term ocular surface stabilization and improved VA in SJS patients.

Corneal neovascularization: updates on pathophysiology, investigations & management.

Objective. Corneal neovascularization is a sight-threatening condition affecting more than 1.4 million people per year. Left untreated, it can lead to tissue scarring, oedema, lipid deposition, and persistent inflammation that may significantly affect visual prognosis and quality of life. The aim was to review the recent evidence relating to the pathophysiology, investigations and management of corneal neovascularization. Methods. Literature review of prospective and retrospective studies, clinical trials and animal models relating to the pathophysiology, investigation and management of corneal neovascularization. Results. Corneal neovascularization is characterized by the invasion of new blood vessels into the cornea caused by an imbalance between angiogenic and antiangiogenic factors that preserve corneal transparency as a result of various ocular insults and hypoxic injuries. Risk factors that have been implicated in the pathogenesis of the disease include contact lens wear, ocular surface disease, trauma, previous surgery and herpes. The results highlighted the current and future management modalities of corneal neovascularization, which includes corneal transplantation, laser - phototherapy, injections and topical treatment. Conclusion. The future of corneal neovascularization is promising and this paper discusses the upcoming revolution in local gene therapy. Abbreviations. HSK = herpes stromal keratitis, VEGF = vascular endothelial growth factor, VEGFR-1 = VEGF Receptor-1, FGF = Fibroblast growth factor, PDGF = Platelet-derived growth factor, IL-6 = interleukin-6, IL-7 = interleukin-7, IL-8 = interleukin-8, IRS-1 = insulin receptor substrate-1.

AAV vector-meditated expression of HLA-G reduces injury-induced corneal vascularization, immune cell infiltration, and fibrosis.

Over 1.5 million individuals suffer from cornea vascularization due to genetic and/or environmental factors, compromising visual acuity and often resulting in blindness. Current treatments of corneal vascularization are limited in efficacy and elicit undesirable effects including, ironically, vision loss. To develop a safe and effective therapy for corneal vascularization, adeno-associated virus (AAV) gene therapy, exploiting a natural immune tolerance mechanism induced by human leukocyte antigen G (HLA-G), was investigated. Self-complementary AAV cassettes containing codon optimized HLA-G1 (transmembrane) or HLA-G5 (soluble) isoforms were validated in vitro. Then, following a corneal intrastromal injection, AAV vector transduction kinetics, using a chimeric AAV capsid, were determined in rabbits. One week following corneal trauma, a single intrastromal injection of scAAV8G9-optHLA-G1 + G5 prevented corneal vascularization, inhibited trauma-induced T-lymphocyte infiltration (some of which were CD8+), and dramatically reduced myofibroblast formation compared to control treated eyes. Biodistribution analyses suggested AAV vectors persisted only in the trauma-induced corneas; however, a neutralizing antibody response to the vector capsid was observed inconsistently. The collective data demonstrate the clinical potential of scAAV8G9-optHLA-G to safely and effectively treat corneal vascularization and inhibit fibrosis while alluding to broader roles in ocular surface immunity and allogenic organ transplantation.

Corneal neovascularization and biological therapy.

Corneal avascularity is necessary for the preservation of optimal vision. The cornea maintains a dynamic balance between pro- and antiangiogenic factors that allows it to remain avascular under normal homeostatic conditions. Corneal neovascularization (NV) is a condition that can develop in response to inflammation, hypoxia, trauma, or limbal stem cell deficiency and it is a significant cause of blindness. New therapeutic options for diseases of the cornea and ocular surface are now being explored in experimental animals and clinical trials. Antibody based biologics are being tested for their ability to reduce blood and lymphatic vessel ingrowth into the cornea, and to reduce inflammation. Numerous studies have shown that biologics with specificity for VEGF A such as bevacizumab and ranibizumab (a recombinant antibody and an antibody fragment, respectively) or anti-tumor necrosis factor-α microantibody, are effective in the treatment of corneal neovascularization.

Recorrência de doença herpética corneal após tratamento para neovascularizaçäo de córnea com argon laser / Recurrence of corneal herpetic disease after argon laser treatment

Considerada como um dos principais fatores associados à rejeiçäo de transplante de córnea, neovascularizaçäo de córnea é de difícil tratamento e continua a ser desafio para o cirurgiäo de córnea. Dentre as várias formas de tratamento se inclui fototerapia com laser de argônio, que tem se mostrado eficaz em diminuir neovascularizaçäo de córnea, e está associada a baixo índice de complicaçöes como irite leve, hemorragia intracorneal e deposiçäo secundária de lipídios. Descreveu-se dois casos de recorrência de doença herpética corneal em pacientes com neovascularizaçäo de córnea tratados com fotocoagulaçäo por laser de argônio e discutiu-se possíveis fatores relacionados a essa complicaçäo

Histological evaluation of phthalocyanine mediated photodynamic occlusion of corneal neovascularization enhanced by hyperbaric oxygenation.

PURPOSE: We evaluated the effective irradiation parameters for photodynamic thrombosis of experimental corneal neovascularization enhanced by simultaneous hyperbaric oxygenation. METHODS: Neovascularization was provoked in both eyes of each of 35 albino rabbit corneas using the intracorneal suture technique. The lasered animals were divided in 3 groups. Group 1 (10 rabbits) was treated under hyperbaric conditions (28 atm for 25 min.); group 2 (5 rabbits) was treated breathing pure oxygen delivered by a face mask; group 3 (10 rabbits) was treated breathing room air. The fourth group (10 rabbits) was used for control. Animals were anaesthetized, and irradiation of new corneal vessels was carried out 30 minutes after the injection of 5 mg/kg chloroaluminum sulfonated phthalocyanine. A 670 nm diode laser with a power 4 mW and a spot diameter 350 mm was used. Exposure times necessary for vascular occlusion were registered. Histological examination was carried out at the end of the follow-up time. RESULTS: Exposure times were significantly lower in groups 1 and 2 as compared to group 3 (1.75 +/- 0.15 min., 3.1 +/- 0.4 min., and 4.75 +/- 0.15 min. respectively). Total light dose averaged 490 J/cm,2 870 J/cm,2 and 1330 J/cm,2 respectively. Histological examination revealed thrombus formation in the targeted vessels of all three investigated groups. CONCLUSION: Combination of PDT with hyperbaric oxygenation results in an acceleration of the photodynamic process and provides for a possibility of significant reduction of photodynamic dose.