Bi-weekly Subconjunctival Injection of Bevacizumab for Corneal Neovascularization after Burn Injury

Purpose: We report two cases of corneal neovascularization (NV) after burn injury successfully treated by subconjunctival bevacizumab injections at 2-week intervals.Case summary: Three bi-weekly subconjunctival injections of bevacizumab were administered to two patients with corneal NV after burn injury. In our first patient, corneal NV was markedly reduced by bevacizumab injection. The patient exhibited with a clear cornea and improved visual acuity (20/30) after treatment. Eleven weeks after the last injection, the cornea remained clear, with clinical regression of smaller vessels; the improvement in visual acuity was maintained. In the second case, the diameter of the vessels, hemorrhagic lesions, and corneal edema decreased/regressed, with improvement of the visual acuity to 20/25; these improvements persisted for 12 weeks after the last subconjunctival injection.Conclusions: Our results suggest that bi-weekly subconjunctival injection of bevacizumab is well-tolerated and effective for inhibiting chronic corneal NV after burn injury.

A Comparative Study Between Preoperative Subconjunctival Bevacizumab Injection And Postoperative Topical Application In Prevention Of Recurrence After Excision Of Primary Pterygium In Egyptian Patients

Purpose to compare between recurrence incidence after primary pterygium excision when using preoperative subconjunctival injection of Bevacizumab (Avastin) and using it as a postoperative eye drops. Methods thirty two eyes of thirty patients (two patients had bilateral pterygium) with primary pterygia were clinically examined, classified into 3 groups and operated by simple excision with bare sclera technique. Group 1 included 10 patients received Bevacizumab (Avastin) in the form of eye drops (10 mg/ml) 3 times daily for 6 days postoperative. Group 2 included 10 patients received preoperative Bevacizumab in the form of subconjunctival injection (1.25 mg/0.05ml) single dose 1 week preoperative. Group 3 included 10 patients (12 eyes) 2 patients with bilateral Pterygium didn’t receive any form of Bevacizumab. Postoperative follow up was done clinically and by serial photography at 1 week, 1 month, 3 months and 6 months searching for signs of recurrence and/or complications. Results The results showed different grades of recurrence in 18 eyes of 32.True recurrence was seen in 7 patients of 18 (1 patient in group 1, 2 in group 2 and 4 in group3).Recurrence grades in group 1and 2 who used the Bevacizumab (20%grade II, 50% grade III, and 30% grade IV). Recurrence could be predicted by 100% depending on fibrovascular tissue appearing in the surgical bed at 3 months postoperative (P value 0.038).Preoperative fleshy pterygium has high statistical significance in realation to recurrence(P value = 0.006).Patient’s sex, residence and occupation had no statistically significant value in the process of recurrence (P value > 0.05). Patients with recurrent Pterygia (in group 1&2) had statistically significant changes in the corneal K- readings at 3 months and 6 months.No significant difference in the limbal or central corneal thickness in the operated eye and the other eye (Pvalue > 0.05). Conclusion Bevacizumab (Avastin) is a well tolerated drug with multiple drug delivery methods.The eye drops give better results than the subconjunctival injection.Appearance of fibrovascular tissue in the surgical bed at 3 months predict the recurrence by 100%. Preoperative fleshy pterygia will mostly recur again whatever Bevacizumab form was used .The corneal thickness by anterior segment OCT has no role in prediction or detection of early pterygium recurrence.

Phacoemulsification and calculation of intraocular lenses in patients given keratorefractive surgery. Part 1

Rationale.Qualitative rehabilitation of patients with cataracts who had keratorefractive surgeries depends on phacoemulsification technology and correctly calculated optical power of the IOL. Purpose: present the author’s own approaches to the development of surgical tactics for treating patients with cataracts who underwent keratorefractive surgeries. Material and methods. The complicated character of cataract surgery performed after LASIK — deterioration of visualization due to the presence of an optical ablation zone and a transition zone (6–7 mm) — is successfully compensated by instillations of a dispersed viscoelastic (methylcellulose) onto the surface of the cornea. Another factor is the deepening of the anterior chamber in high myopia, which is uncomfortable for manipulation and may require a lowerlevel of irrigation (up to 60 mm Hg). The technology of surgery performed after radial keratotomy (RK) requires utmost attention to the prevention of surgical astigmatism that could emerge due to biomechanical instability of the cornea. To ensure such prevention, paracentesis is performed outside the zone of keratotomy scars, the main 2.2 mm incision is made after capsulorhexis in the sclerolimbal zone, and at theend of the operation, a subconjunctival injection is performed in the conjunctival zone of the knife keratom entrance for the tamponade ofthe outer part of the incision without suturing. These techniques made it possible to successfully perform more than 200 operations and achieve a favorable course of the postoperative period from the first day. Fast adaptation of the incision (1–2 days), uncomplicated course of the postoperative period and the absence of induced astigmatism are important advantages of this technology. Conclusion. The choice of surgical technology, taking into account the initial state of the eye after LASIK and RK surgeries, is an important task. Yet the main problem with which the doctor is faced after keratorefractive surgery is the difficulty of calculating the optical power of the IOL which must take into account the special needs of the patient with a particular refractive history, which will be reported in part 2 of the article.

Er:YAG laser-assisted filtration surgery: initial results in rabbits

Background Glaucoma is a leading cause of global blindness, especially preventable blindness. The increased prevalence of glaucoma has led to a growing demand for newer, safer, more rapid, and simpler treatments for the reduction of intraocular pressure (IOP). In this study, we evaluated the safety and feasibility of performing filtration glaucoma surgery with an Ab-Interno Er:YAG laser in rabbits. Methods Nine New Zealand White rabbits age 16 weeks were studied. After subconjunctival injection of mitomycin C (MMC), a novel Ab-Interno Er:YAG laser probe was inserted into the anterior chamber (AC) through a clear corneal 1 mm paracentesis and directed at the trabecular meshwork adjacent to the MMC injection area. A pulsed laser beam was applied to create a patent sclerostomy connecting the AC to the subconjuctival space, resulting in a filtering bleb. The laser system used was the Er:YAG laser system - LAS25-FCU, (Pantec Biosolutions AG, Liechtenstein). Parameters used: Wave lengh: 2940 nm, Pulse length: 100–400 μsec,frequency: 250 Hz. Average laser power in accordance to the fiber tip diameter: 0.85 W(range 0.8–0.92 W). Complete ocular exams, including IOP measurements, were performed on 1, 7, 14, and 23 days postoperatively. Three rabbits were sacrificed on days 1, 14, and 23, and histological examinations were performed on all nine eyes. Results All procedures resulted in a functional medium-large superior bleb without significant complications. The bleb was sustained in all rabbits by day 14 and in one of the three rabbits that reached the last follow-up at 23 days. No cases of postoperative hypotony were observed. There was a transient significant reduction in mean IOP on postoperative days 5 and 7 (P = 0.028). Histopathological analysis revealed a patent full-thickness scleral tunnel with only a minor degree of surrounding coagulation necrosis. Conclusions The Ab-Interno laser sclerostomy procedure is potentially safe and effective based on initial experience in an in-vivo rabbit animal model.

Ion-Complex Microcrystal Formulation Provides Sustained Delivery of a Multimodal Kinase Inhibitor from the Subconjunctival Space for Protection of Retinal Ganglion Cells

Glaucoma is the leading cause of irreversible blindness worldwide. Elevated intraocular pressure (IOP) is one of the major risk factors for glaucoma onset and progression, and available pharmaceutical interventions are exclusively targeted at IOP lowering. However, degeneration of retinal ganglion cells (RGCs) may continue to progress despite extensive lowering of IOP. A complementary strategy to IOP reduction is the use of neuroprotective agents that interrupt the process of cell death by mechanisms independent of IOP. Here, we describe an ion complexation approach for formulating microcrystals containing ~50% loading of a protein kinase inhibitor, sunitinib, to enhance survival of RGCs with subconjunctival injection. A single subconjunctival injection of sunitinib-pamoate complex (SPC) microcrystals provided 20 weeks of sustained retina drug levels, leading to neuroprotection in a rat model of optic nerve injury. Furthermore, subconjunctival injection of SPC microcrystals also led to therapeutic effects in a rat model of corneal neovascularization. Importantly, therapeutically relevant retina drug concentrations were achieved with subconjunctival injection of SPC microcrystals in pigs. For a chronic disease such as glaucoma, a formulation that provides sustained therapeutic effects to complement IOP lowering therapies could provide improved disease management and promote patient quality of life.

A Brief Review on the Prevalence, Diagnosis Prevention of Infectious Bovine Keratoconjuctivitis

This seminar review is aimed to provide information about the IBK which results in ocular pain and loss of vision that would result in the reduction of the market price of the affected animal. Infectious Bovine Keratoconjuctivitis (IBK) or ‘pink eye’ is a common and highly contagious ocular disease. The disease is caused by the bacteria family Moraxellaceae, genus Moraxella and species Moraxella bovis. M. bovis is a gram-negative rod. The occurrence and distribution of the disease are worldwide and the persistence of the disease from year to year is by means of infected animals, which can act as carriers. Transmission is unusual in the absence of flies and occurs generally in their presence. A number of factors such as tall grass, weeds, dust, face flies and ultraviolet radiation, and other stress factors contribute to the disease occurrence. The pathogenesis of IBK is likely associated with collagenase release from epithelial cells, fibroblasts, and neutrophils. Hydrolytic enzymes of M. bovis possess the ability to degrade lipids, mucopolysaccharides, and matrix proteins, which may contribute to corneal ulceration. The first signs of pinkeye are characterized by excessive tearing, blinking, photophobia, and swelling of the eyelids and conjunctiva. As the disease progresses, the ocular discharge becomes purulent. The disease is usually diagnosed with clinical signs like excessive lacrimation and culturing of the bacteria from ocular exudates. IBK is differentially diagnosed from M. bovis, Pasteurella multocida, IBRT, and Thelaziasis. Drugs may be delivered to the eye in several ways: subconjunctival injection, topical application, and systemic administration to treat the diseases. Vaccination and fly control are some of the prevention and control measures. This disease is economically very important which causes severe ocular disorder in cattle which may result in the suffering of the animal from pain and loss of vision thereby economic loss due to bodyweight loss by the stress from pain, inability to feed properly, and the blindness that reduces the price of sale. Therefore, it is recommended that the susceptible cattle should be housed to avoid exposure to UV radiation and the populations of face flies should be controlled to minimize the incidence and transmission of IBK.

Subconjunctival administration of low-dose murine allogeneic mesenchymal stromal cells promotes corneal allograft survival in mice

Background Systemic administration of mesenchymal stromal cells (MSCs) has been efficacious in many inflammatory disease settings; however, little data are available on the potential immunomodulatory effects following local MSC administration in the context of corneal transplantation. The purpose of this study was to assess the potential of subconjunctival injection of MSCs to promote corneal allograft survival. Methods MSCs were isolated from female C57BL/6 (H-2k) or Balb/c (H-2d) mice and extensively characterized. An allogeneic mouse corneal transplant model was used with Balb/c mice as recipients of C57BL/6 grafts. A dose-finding study starting with 5 × 105 MSCs injected subconjunctivally at day − 7 was tested first followed by a more clinically translatable low-dose single or dual injection strategy on day − 1 and day + 1 before/after transplantation. Graft transparency served as the primary indicator of transplant rejection while neovascularization was also recorded. Lymphocytes (from draining lymph nodes) and splenocytes were isolated from treatment groups on day 2 post-transplantation and characterized by flow cytometry and qRT-PCR. Results Both high- and low-dose injection of allogeneic MSCs on day − 7 led to 100% graft survival over the observation period. Moreover, low-dose dual subconjunctival injection of 5 × 104 allogeneic MSCs on day − 1 or day + 1 led to 100% allograft survival in transplant recipients (n = 7). We also demonstrate that single administration of allogeneic MSCs on either day − 1 or day + 1 promotes rejection-free graft survival in 100% (n = 8) and 86% (n = 7) of transplanted mice, respectively. Early time point ex vivo analysis suggests modulation of innate immune responses towards anti-inflammatory, pro-repair responses by local MSC administration. Conclusion This work demonstrates that low-dose subconjunctival injection of allogeneic MSCs successfully promotes corneal allograft survival and may contribute to refining future MSC immunotherapies for prevention of corneal allograft rejection.

Development of Triamcinolone Acetonide-Loaded Microemulsion as a Prospective Ophthalmic Delivery System for Treatment of Uveitis: In Vitro and In Vivo Evaluation

Treatment of uveitis (i.e., inflammation of the uvea) is challenging due to lack of convenient ophthalmic dosage forms. This work is aimed to determine the efficiency of triamcinolone acetonide (TA)-loaded microemulsion as an ophthalmic delivery system for the treatment of uveitis. Water titration method was used to construct different pseudo-ternary phase diagrams. Twelve microemulsion formulations were prepared using oleic acid, Cremophor EL, and propylene glycol. Among all tested formulations, Formulation F3, composed of oil: surfactant-co-surfactant (1:1): water (15:35:50% w/w, respectively), was found to be stable and showed acceptable pH, viscosity, conductivity, droplet size (211 ± 1.4 nm), and zeta potential (−25 ± 1.7 mV) and almost complete in vitro drug release within 24 h. The in vivo performance of the optimized formulation was evaluated in experimentally uveitis-induced rabbit model and compared with a commercial TA suspension (i.e., Kenacort®-A) either topically or by subconjunctival injection. Ocular inflammation was evaluated by clinical examination, white blood cell count, protein content measurement, and histopathological examination. The developed TA-loaded microemulsion showed superior therapeutic efficiency in the treatment of uveitis with high patient compliance compared to commercial suspension. Hence, it could be considered as a potential ocular treatment option in controlling of uveitis.

Corneal Ulcer in Dogs and Cats: Novel Clinical Application of Regenerative Therapy Using Subconjunctival Injection of Autologous Platelet-Rich Plasma

Background: Corneal ulcer could be a major source of distress in small animals, with many contributing agents. In recent years, few studies evaluated the efficacy of platelet-rich plasma (PRP) in healing corneal ulcers.Aim: This study aimed to assess the ability of subconjunctival injection of autologous PRP in the treatment of corneal ulcers in dogs and cats as well as estimate the expression of matrix metalloproteinase (MMP)-2, MMP-9, and oxidative stress biomarkers in these patients.Methods: A total number of 28 animals (16 cats and 12 dogs) were enrolled in this study. Each animal was subjected to clinical, neurologic, and ophthalmic examinations where the type of ulcer was documented. Tear samples were collected for evaluation of oxidative biomarkers and MMPs; conjunctival swabs were taken to identify the involved organism. PRP was prepared from each animal and given as subconjunctival injection; numbers of injections were done according to case response. Clinical follow-up was done and documented for each case.Results: In cat patients, female and Persian cats were most affected; unilateral and superficial ulcers were most recorded. In male dogs, unilateral, and superficial ulcers were most recorded. FHV-1 was most identified in cats, while Staphylococcus aureus was most identified in dogs. Numbers of injections needed to achieve healing were recorded, with 50% of dogs needing two injections with 1-week intervals and 50% of cats needed three injections with 1-week intervals. Alterations in both oxidative biomarkers and MMPs were recorded in affected animals.Conclusion: The use of autologous PRP as a subconjunctival injection in treating corneal ulcers in dogs and cats is effective. The number of injections is the case and corneal ulcer type-dependent.Clinical Significance: Autologous PRP as a subconjunctival injection in treating corneal ulcer is a relatively cheap, safe method and can be done in the clinical setting.