Article

Laser Photocoagulation of Feeder Vessels in Lipid Keratopathy

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Abstract

Argon laser photocoagulation was performed on rabbit eyes with lipid keratopathy. The lipid keratopathy was induced by rendering 30 rabbits hypercholesterolemic and inciting neovascularization by insertion of corneal sutures. The number of laser shots required to occlude corneal vessels increased with the suture residence time, whereas the number of limbal shots remained essentially constant. Corneal opacification and cholesterol content increased as a result of greater suture residence time and unexpectedly from the laser applications which were administered in a single treatment session.

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... It can be observed clinically in patients with infectious keratitis, trauma, alkali burns, or contact lens wear. 1 Neovascularization can help corneal wound healing, but it can also lead to a reduction in corneal transparency and, consequently, significant visual impairment. In addition, it can worsen the prognosis of corneal transplantation because of the loss of immune privilege in the transplanted cornea. 2 Inhibition of corneal neovascularization has been reported in several studies through medications like steroids, NSAIDs, and cyclosporine A; 3-7 laser therapies like thermal argon laser photocoagulation; [8][9][10] and surgeries like limbal transplantation and amniotic membrane transplantation. 11,12 However, there is currently no definitive treatment because of side effects and considerations of clinical safety. ...
... Groups treated with 40 μmol/L (4, 5, 6), 80 μmol/L (7,8,9), or 160 μmol/L (10, 11, 12) topical curcumin. Initial neovascularization of the cornea was observed (1,4,7,10). Three days after treatment, neovascularized areas had slightly regressed in the control and 40 μmol/L groups (2, 5), but neovascularized areas were significantly reduced in the 80 and 160 μmol/L groups compared with the control group (8,11). ...
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To investigate the anti-angiogenic effect of topical curcumin on corneal neovascularization in a rabbit model. One week after suturing, six eyes were treated with balanced salt solution (BSS) (group A), and six eyes were treated with curcumin 40, 80, or 160 micromol/L (groups B, C, and D, respectively), topically two times a day. After one week, light microscopy was used to analyze corneal neovascularization. The concentration of vascular endothelial growth factor (VEGF) mRNA in the corneal tissue was measured by reverse transcriptase-polymerase chain reaction (RT-PCR), and the activation of NF-kappaB was examined by immunofluorescent staining. Seven days after treatment, the sizes of the neovascularized areas were significantly reduced in groups B (50.1% +/- 6.7%), C (43.2% +/- 8.1%), and D (29.5% +/- 7.8%) compared with group A (69.5% +/- 1.5%) (p < 0.05). The corneal VEGF mRNA levels were significantly lower in groups C and D than they were in group A (p < 0.05). Immunofluorescent staining showed that phospho-NF-kappaB staining of the corneal tissue was weaker in group C than it was in groups A and B. Topical application of curcumin was useful in reducing experimental corneal neovascularization and can be used to inhibit angiogenesis in the cornea.
... Iritis, glaucoma, and decreased visual acuity are serious conse- quences [20]. A significant number of anti-angiogenic pharmaceutical strategies and therapeutic procedures have been established in order to treat corneal angiogenesis, such as steroids [21], angiostatin [22], methotrexate [23], photocoagulation [24], topical ascorbate 10 % [25] , conjunctival recession, β-irradiation , cauterization, heparin [26], thalidomide [27] , and cryo- therapy [28]. Regardless of the therapeutic efficiency, some of these treatments have been connected with side effects such as glaucoma and cataract [28]. ...
Article
To evaluate the efficacy of mesenchymal stem cells (MSCs) to ameliorate the consequences of corneal alkali injuries. Corneal alkali injuries were created in 30 rabbit eyes. The MSC group (n = 15) were treated with intrastromal and subconjunctival injections of phosphate-buffered saline (PBS) containing 2 × 10(6) MSCs and topical application. The control group (n = 15) was treated with PBS by the same applications forms. Drops of standard treatment (ascorbate 10 %, citrate 10 %, tobramycin, dexamethasone, Cyclogyl) were instilled for 2 weeks. Rabbits underwent slit-lamp examination, fluorescein staining, photography, and were evaluated for corneal neovascularization, opacification, and epithelial defects. Tear secretion and IOP were also evaluated. Furthermore, the concentration of Serumglutamic-pyruvic transaminase (SGPT) and vascular endothelial factor (VEGF) were measured. Immunohistochemistry was also performed for a-SMA and Ki-67. Eyes treated with MSCs showed better recovery. The mean neovascularized area was significantly smaller in the MSC group (p < 0.05). A significant difference in the degree of corneal opacification and re-epithelialization was also observed, as well as the IOP at 21 and 28 posttraumatic days (p < 0.05). Histology showed that MSCs resulted in almost normal architecture of eye tissues. After the MSCs infusion, SGPT and VEGF levels in cornea were significantly reduced. Immunohistochemistry demonstrated a reduction of a-SMA in the MSC group with higher mitotic-regenerative activity with the presence of Ki67. Our study represents a first step in understanding the possibilities of the MSC approach to treatment of alkali injuries of the cornea and shows that such an approach improves clinical outcomes and leads to better prognosis.
... However, in corneas in which vessels have been established, corticosteroid and NSAID treatments are ineffective. Although laser photocoagulation for corneal NV has been reported [14,15], this method achieves an inadequate effect because of the high incidence of recanalisation and thermal damage to adjacent tissue [16]. Other treatments including photodynamic therapy, fine needle diathermy and conjunctival, limbal and amniotic membrane transplantation [17][18][19] have limited clinical efficacy and also cause a multitude of undesirable side effects. ...
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Corneal neo-vascularisation (NV) is a major sight-threatening condition and is caused by infections, degenerative disorders, inflammation and long-time contact lens wear. Corneal NV occurs when the balance between angiogenic and antiangiogenic factors is tipped towards angiogenic molecules. The abnormal vessels may decrease corneal clarity and vision, lead to inflammation and corneal scarring and worsen the prognosis of penetrating keratoplasty if needed.There is no definite therapeutic approach for cornea NV. Medical and surgical therapies used to reduce corneal NV include corticosteroids and non-steroidal anti-inflammatory agents, laser photocoagulation and needle diathermy. Many of these therapies not only have demonstrated limited success but also have associated adverse effects. Therefore, it is very necessary to provide novel therapeutic approaches. Recently, anti-vascular endothelial growth factor (anti-VGEF) therapy has been introduced for the management of corneal NV.Herein, we hypothesise the use of silicate nanoparticles (SiNPs) as a novel treatment for corneal NV. The penetration rate of SiNPs into the cornea is attributed to the size of nanoparticles. Therefore, different sizes of SiNPs (20–50 nm) would be prepared and loaded onto the tissue to determine corneal permeability towards them. In addition, SiNPs would be administered into the eye by topical, subconjunctival and corneal intrastromal injection and accumulate in newly formed vessels. This hypothesis has been developed by emphasising on the synthesis of SiNPs, characterisation of size-dependent properties and surface modification for the preparation of homogeneous nanocomposites, generated by a reverse micro-emulsion method. As the importance of concentration, shape and/or size of SiNPs could be key factors exerting their antiangiogenic effects, we suggest using 20–30-nm SiNPs to enhance their ability to penetrate into the corneal epithelium. We hypothesise that topical, subconjunctival and corneal intrastromal injections of SiNPs may effectively inhibit and treat corneal NV. Controlled experimental studies on rabbits are needed to test whether SiNPs are able to effectively inhibit VEGF-induced angiogenesis in every segment of the eye including anterior, middle (ciliary body and trabecular mesh work) and posterior segments.
... Many methods have been tried to treat corneal vascularization however the success rate was variable. These methods include; argon laser photocoagulation (Mendelsohn et al., 1986), photodynamic therapy (PDT) with verteporfin (Fossarello et al., 2003;Yoon et al., 2007), fine needle diathermy (Pillai et al., 2000), topical, subconjunctival, intracorneal Avastin Ò injections (Regenfuss et al., 2009;Vassileva and Hergeldzhieva, 2009) and beta ray therapy (Vassileva and Hergeldzhieva, 2009;Mailath and Peter, 1972). ...
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We describe a case of significant regression of aggressive, deep and superficial corneal vascularization using photodynamic therapy (PDT) with verteporfin, repeated subconjunctival injections of Avastin®, plus topical cyclosporin-A 1% drops. The area of the corneal vascularization was treated with PDT with verteporfin. The subconjunctival space - next to the area of vascularization - was injected with Avastin® (1.25 mg/0.05 ml), immediately after PDT, and then for two more times during the follow-up period. The patient was kept on topical cyclosporin and prednisolone acetate. The outcome was evaluated clinically and photographically for 13 months. Corneal vascularization regressed significantly. No adverse effects were observed, neither locally or systemically. PDT with verteporfin, repeated subconjunctival injections of Avastin®, and topical cyclosporin-A drops appear to be safe and effective in treating aggressive corneal vascularization.
... Studies attempted to treat corneal neovasculature by the application of angiogenesis suppressor factors such as angiostatin or PEDF, have been conducted, however, they eventually failed. Corneal laser photocoagulation using an argon laser may accompany recurrence of neovascularization, heat injury of adjacent tissues, and the consequent increase of inflammation [9]. As surgical therapy, limbal transplantation [23] or amniotic membrane transplantation [6] has been attempted, however, positive effects were not reported. ...
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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.
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The use of digital fluorescein corneal angiography to assist argon laser photocoagulation is reported. Photocoagulation was performed on the vascular supply of lipid keratopathy in the left eye of a 44-year-old woman.
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To describe the effect of photodynamic therapy (PDT) using verteporfin (Visudyne) on corneal neovascularization (CNV) in two patients. Two patients with corneal neovascularization were treated with a nonthermal laser light at 689 nm delivered 15 min after an intravenous infusion of verteporfin. Postoperative outcome of neovascularization was followed clinically (inflammation, intraocular pressure, and visual acuity) and photographically [color photographs and corneal fluorescein and indocyanine green (ICG) angiography] for a minimum of 6 months. Successful photothrombosis of corneal neovascularization was obtained immediately after treatment in the two patients, and regression was verified by corneal fluorescein and ICG angiography. In one case, partial vessel recanalization was observed after 1 month, and treatment was repeated, with complete regression of new vessels. No relevant side effects were observed in our cases. PDT with verteporfin is an effective and safe procedure indicated for patients with corneal neovascularization; however, multiple sessions may be required.
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Corneal neovascularization is a common clinical entity. Although visual acuity is usually impaired and corneal function compromised, there has been only limited success in the clinical management of this condition. We evaluated the efficacy of laser photocoagulation of neovascularization in the rabbit cornea. New vessel formation was provoked by the placement of sutures in the corneas. Rose bengal was injected intravenously and new vessels in the upper part of the corneas were treated with an argon laser. The lower halves were used as controls. Eighteen rabbits were divided into 2 groups. In group A neovascularization was treated 28 days after suture removal, when corneal inflammation had regressed. In group B treatment was performed 3 days after suture removal, when the cornea still exhibited marked inflammation. Postoperatively, the corneas were studied by slit-lamp microscopy, fluorescein angiography, and light, as well as electron microscopy. In group A, treatment led to the immediate occlusion of the vessels and to their gradual disappearance during the course of 3 months. In group B, no occlusion was seen during the 3-month follow-up period. The main histologic findings in the occluded vessels were endothelial cell disruption and degeneration, and the formation of clots. Our results suggest that argon laser photocoagulation using rose bengal is an effective method of occluding corneal new vessels, providing there is no corneal inflammation at the time of treatment.
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The presence of vessels has a negative influence on corneal transplant survival. Closure of such vessels prior to transplantation may improve the transplant results, and this might be achieved by irradiating the vessels with argon laser light after intravenous administration of a photosensitizer, e.g. bacteriochlorin a (BCA). A suture-induced corneal neovascularization model in rats was set up to test this hypothesis. Suture-induced vessels in the cornea of male Wistar rats were irradiated with argon laser light after intravenous administration of BCA. We applied irradiation of varying energy levels and duration and assessed the changes in the vessels by slit-lamp examination, fluorescein angiography and histology. Suture-induced corneal vessels in the rat could be used effectively to study photothrombosis therapy. Intravenous administration of BCA prior to irradiation (lambda = 514.5 nm) of the corneal vessels led to vessel closure at lower energy levels and of longer duration than occurred with laser treatment alone. Suture-induced corneal neovascularization in the rat can be used as a model to study the efficacy of photothrombosis therapy. BCA can be used to enhance the rate and duration of vessel closure.
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Sixty-three cases of vascularised lipid keratopathy were treated with the argon laser to occlude feeder vessels which had been identified by fluorescein angiography. There was a reduction in extent in 62% and density in 49%. Visual acuity was improved in 48%. Six patients had keratoplasties shortly after treatment, none of which showed graft rejection. Minor complications included temporary haemorrhage into the cornea and iris atrophy. A more serious problem was severe corneal thinning after resorption of lipid. The patients had to be carefully followed up and maintained on a low dose of topical steroid.
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In central nervous system (CNS) injury induced by stroke, or by impact injury to the spinal cord (Balentine, 1985), vascular abnormalities leading to thrombosis or thromboembolism are often intimately involved in the expression of the clinical severity of the final disease state. However, in the interest of reproducibility, most animal models of “stroke” feature induction of cerebral ischemia by mechanical occlusion of brain arteries (Garcia, 1984; Pulsinelli and Brierley, 1979). The participation of thrombotic processes is thus obviated. In contrast, mechanical induction of experimental spinal cord injury is considered to facilitate rather realistic development of the manifestations seen clinically. Yet, exposure of the cord tissue prior to injury and disruption of the cord tissue at the time of ipjury complicate the reproducibility of the experiments (Koozekanani et al, 1976; Ford, 1983; Gale et al, 1985) and make it difficult to ascertain the contribution of vascular injury, whether direct or indirect, to the final outcome.
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: To determine the efficacy of the topical application of ascorbic acid for the treatment of corneal neovascularization. : Corneal neovascularization was induced in 16 rabbits with a silk suture in the corneal stroma (32 eyes). At 1 week after suturing, 15 rabbits were divided into 3 groups and were treated with topical ascorbic acid at 3 different concentrations: 10 mg/mL (group 1), 1 mg/mL (group 2), and 0.5 mg/mL (group 3). All treatments were added in the right eye twice a day. All left eyes (15 eyes) and both eyes of the 16th rabbit were used as experimental controls and a normal control, respectively. The area of corneal neovascularization was measured using light microscopy. The concentrations of vascular endothelial growth factor and matrix metalloproteinase-9 in the corneal tissue were measured. : The neovascularized area was decreased in the treated groups compared with the control group. There was a significant difference in the neovascularized areas between the control and groups 1 and 2. No significant difference was observed between the control and group 3. The concentration of vascular endothelial growth factor was significantly lower in the treated groups than in the control group, but there was no difference between the treated groups. The concentration of matrix metalloproteinase-9 showed a significant difference between the control and treated groups, but no difference between the treated groups. : Topical administration of ascorbic acid may be useful for the treatment of corneal neovascularization.
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The aim of this study was to evaluate the efficacy of topical application of epigallocatechin gallate (EGCG) for the treatment of corneal neovascularization in a rabbit model. Corneal neovascularization was induced in 12 rabbits by placing a black silk suture in the corneal stroma (24 eyes) for a week. After suturing, 1 randomly chosen eye of the 12 rabbits was treated with topical EGCG at 2 different concentrations: 0.01% (group 1) and 0.1% (group 2), whereas the contralateral eyes were treated with sterilized balanced salt solution as the control. All eye drops were applied for 2 weeks after suturing. The suture materials were removed from all eyes on day 7. The surface area of corneal neovascularization was measured and analyzed in all eyes on days 7 and 14. On day 14, all eyes were extracted to measure the concentrations of vascular endothelial growth factor (VEGF) messenger RNA and cyclooxygenase-2 (COX-2) protein. The surface area of induced corneal neovascularization was significantly smaller only in group 2 compared with that of the control group on days 7 and 14 (P < 0.001). The change in surface area of corneal neovascularization after removal of the suture material was not significantly different between all 3 groups. VEGF messenger RNA levels were significantly lower in group 2 than in the control group (P < 0.001). The concentration of COX-2 was significantly lower in group 2 than in the control group (P = 0.043), but no significant difference was observed between group 1 and the control group. Topical administration of EGCG effectively inhibits corneal neovascularization in rabbits. This inhibitory effect is probably related to the suppression of VEGF and COX-2 meditated angiogenesis.
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Purpose: The aim of this study was to investigate transmission of topical silicate nanoparticles (SiNPs) through the corneal stroma, anterior chamber, and vitreous fluids by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and inductively coupled plasma atomic emission spectrometry (ICP-AES), respectively. Methods: SiNPs with a mean diameter of 40.6 ± 5.6 nm determined by dynamic light scattering were used in this study. The permeability of SiNPs was examined across isolated corneal buttons over a 30-minute period. To visualize the transport and diffusion of nanoparticles through the corneal tissue, SiNPs were applied over the corneal surface and evaluated at 5 and 30 minutes after SiNPs loading for SEM and 15 minutes for TEM. Sections of 10-μm thickness were cut and visualized using SEM. TEM study was performed on 70- to 90-nm-thick sections. ICP-AES was used to determine the concentration of SiNPs. Results: The determined range of synthesized SiNPs by dynamic light scattering was 40 nm (41.9 ± 5.6 nm). Transmission of SiNPs through the corneal stroma was shown successfully with electron microscopic (SEM and TEM) images. The ICP-AES results revealed SiNPs in the anterior chamber and vitreous fluid. Conclusions: Topical administration of SiNPs, as a noninvasive, and available modality with acceptable penetration through the corneal stroma and deep into the intraocular fluids including the anterior chamber and vitreous cavity, may be considered as a suitable alternative to invasive intravitreal injection of other expensive antineovascularization agents.
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To investigate the accumulation of new photosensitizers (PSs), dendrimer porphyrin (DP, free DP), and DP encapsulation into polymeric micelles (DP-micelle) and the efficacy of photodynamic therapy (PDT) in an experimental corneal neovascularization model in mice. Corneal neovascularization was induced by suturing 10-0 nylon 1 mm away from the limbal vessel in C57BL6/J mice. To determine the accumulation of free DP and DP-micelle, 10 mg/kg free DP or DP-micelle was administered by intravenous injection 4 days after suture placement. Mice were killed 1, 4, 24, and 168 hours after the injection of PS. Twenty-four hours after the administration of free DP or DP-micelle, mice were treated with a diode laser of 438-nm wavelength at 10 or 50 J/cm(2). Fluorescein angiography was performed before and 7 days after irradiation, and the area of corneal neovascularization was quantified. Free DP and DP-micelle accumulated in the neovascularized area 1 hour to 24 hours after administration. Fluorescence of DP was weaker than that of DP-micelle. Neither DP-micelle nor DP could be detected in normal limbal vasculature. In the PDT experiments using PS, mean residual rates of corneal neovascularization were 10.1% in the mice treated with DP-micelle and 21.6% in the mice treated with free DP at 10 J/cm(2) (P < 0.01). At 50 J/cm(2), mean residual rates of corneal neovascularization were 10.6% in the mice treated with DP-micelle and 13.7% in the mice treated with free DP (P > 0.05). Although corneal neovascularization in PDT-treated mice exhibited significant regression compared with the control group, significant energy-related vessel regression with increasing laser energy could not be observed. PDT with DP-micelle and free DP can provide efficacious treatment of corneal neovascularization.
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Vascularization was induced in rabbit corneas by the application of silver nitrate. Argon laser photocoagulation was applied to the entire length of these corneal vessels with relatively long pulses of energy. Untreated areas of vascularization were used as controls. There was a decrease in the corneal vascularization in the treated areas that exceeded any natural tendency toward remission. The results suggest the efficacy of inducing a remission of corneal vascularization with argon laser photocoagulation.
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Rabbits rendered hypercholesterolemic on a high cholesterol diet while subjected to corneal suture placement to induce neovascularization made useful models for qualitatively and quantitatively studying lipid keratopathy. Forty rabbit eyes were subjected to placement of four sutures located between 1 and 4 mm from the limbus. The neovasculature grew at a constant rate of 0.24 mm/day, unaffected by serum cholesterol levels. Rabbits fed cholesterol prior to surgery were the earliest to display lipid keratopathy, followed by those who began cholesterol feedings on the day of surgery, and last by rabbits who began receiving high cholesterol food seven days following suture placement. A description of the corneal neovascularization process and histopathological and biochemical analyses of the induced lipid keratopathy are presented.
Article
Four cases are presented in which the argon laser was used in the treatment of corneal neovascularization. The usefulness and disadvantages of this mode of therapy are discussed, and the other methods of treating new corneal vessels are listed.
Article
Twenty-two patients with lipid keratopathy were treated with argon laser photocoagulation to the feeder vessels. Two were grafted just over a week after treatment and the corneal discs examined histologically. The remainder of the patients were followed up for a least a year. In 6 cases the visual acuity improved, in 3 deteriorated, and in 10 did not change. The density and extent of the lipid deposition were diminished in 50% of cases. The commonest complications were bleeding into the lipid keratopathy and iris damage. The only serious problem was a disciform type of lipid keratopathy that flared up after treatment. Suggestions are made on improvements in the technique of laser application.
Lipid keratopathy associated with aphakic contact lens wear. Poster presentation at the American Academy of Ophthalmology annual meeting Chicago Illinois
  • F S Brightbill
  • Lange
  • T S Stevens