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Background: Conjunctival sporotrichosis is a rare fungal infection, typically presenting as granulomatous lesions. Its manifestations can be atypical, particularly in immunosuppressed patients. Here, we present a rare case of a Mooren’s ulcer patient with bulbar conjunctival Sporotrichosis presenting as a salmon-pink tumor. Case presentation: A 61-year-old with a history of Mooren’s ulcer and corneal transplantation was diagnosed with conjunctival Sporotrichosis in the left eye. Slit-lamp examination showed conjunctival congestion and edema with a salmon-pink appearance, accompanied by nodules looking like “bread crumbs” scattered under the conjunctiva. After partial tumor resection, histopathology and immunofluorescence staining suggested fungal infection with squamous epithelial hyperplasia. Microbiological testing (DNA) confirmed Sporothrix schenckii as the pathogen. The conjunctival mass resolved without recurrence after local and systemic anti-fungal medicine treatment. Despite the progression of Mooren’s ulcers, which further dissolved and perforated during treatment, aggressive management helped the patient retain some vision. Conclusion: Immunosuppression, such as steroids and tacrolimus eyedrops, may predispose patients to opportunistic infections like sporotrichosis. Oral itraconazole, combined with subconjunctival and topical antifungal therapy, effectively treat severe Sporothrix conjunctivitis. Future studies should explore the balance between antifungal and immunosuppressive therapies to manage coexisting conditions like Mooren’s ulcer while curing fungal infections. [ABSTRACT FROM AUTHOR]

Background/Aim: Diabetic retinopathy (DR), a complication of diabetes, causes damage to retinal blood vessels and can lead to vision impairment. Persistent high blood glucose levels contribute to this damage, and despite ongoing research, effective treatment options for DR remain limited. Dimethyl sulfoxide (DMSO) has shown anti-inflammatory and antioxidant properties in both in vivo and in vitro studies; however, its potential as an anti-inflammatory agent in the context of DR has not yet been explored. This study aimed to assess the effects of subconjunctival injection of DMSO on the progression of DR. Materials and Methods: DR was induced in rats using intraperitoneal injections of streptozotocin (55 mg/kg), confirmed by measuring blood glucose levels and electroretinography (ERG). The rats were divided into five groups: a normal control group (CON), a DR control group receiving PBS injections (DMSO 0), and three DR groups receiving different concentrations of DMSO (98%, 50%, and 10%). Retinal function was evaluated using ERG at weeks 10 and 14, and histological analysis at week 16. Results: The DMSO 50 group had significantly higher B-wave amplitude in ERG compared to the DMSO 0 group (p<0.05). Flicker response amplitudes were also significantly greater in the DMSO 50 and DMSO 10 groups compared to DMSO 0 (p<0.05). Histological examination revealed thinner retinal layers in the DMSO 0 group compared to the CON group, while the DMSO-treated groups showed improved retinal thickness. Conclusion: Subconjunctival injection of 50% DMSO appears to improve retinal function in a rat model of DR. [ABSTRACT FROM AUTHOR]

Simple Summary: Spontaneous chronic corneal epithelial defects are characterized by corneal epithelial dysmaturation and a superficial stromal hyalinized acellular zone that leads to poor attachment between the epithelium and anterior stroma. The conventional treatment of spontaneous chronic corneal epithelial defects involves topical therapy combined with corneal debridement. In cases that fail to achieve corneal healing via corneal debridement, surgical interventions under general anesthesia are required. Mesenchymal stem cells have been used for cell therapy of various corneal diseases in companion animals. In this study, the single use of a subconjunctival injection of canine adipose-derived mesenchymal stem cells provided satisfactory corneal outcomes in canine spontaneous chronic corneal epithelial defects that were nonresponsive to diamond burr debridement. Spontaneous chronic corneal epithelial defects (SCCEDs) are characterized by nonadherent corneal epithelium leading to poor attachment to the corneal stroma. The objective of this study was to characterize corneal outcomes concurrently with the quantification of tumor necrosis factor-alpha (TNF-α) and vascular endothelial growth factor-A (VEGF-A) in tear fluid after the subconjunctival injection of canine adipose-derived mesenchymal stem cells (cAD-MSCs) in canine SCCEDs. Ten eyes with SCCEDs, which were nonresponsive to two rounds of diamond burr debridement, were included in this study. All eyes received a single subconjunctival injection of 1 × 106 cAD-MSCs. Ophthalmic examinations were performed before treatment and on day 7, 14, and 21 after treatment. Tear samples were collected for the quantification of TNF-α and VEGF-A concentrations by a canine multiplex immunoassay. Nine out of ten eyes revealed complete healing by day 21. The mean healing time was 10.89 ± 1.7 days. All eyes showed a decreased degree of ocular discomfort, in accordance with the degree of corneal characteristics. The concentrations of VEGF-A significantly reduced from pre-treatment (4334.91 ± 1275.92 pg/mL) to day 21 post-treatment (3064.61 ± 1028.66 pg/mL). No significant difference in TNF-α concentration was observed before/after treatment. In conclusion, the single use of a subconjunctival injection of cAD-MSCs could be used as an alternative treatment for canine SCCEDs. [ABSTRACT FROM AUTHOR]

Corneal ulcers represent an anxious problem in animals and humans. The alkali burn corneal ulcer is severe and may be associated with damage to most of the corneal structure. The healing of the corneal ulcer is mainly complicated by the impairment of vision. The striving to find a new therapy that promotes the healing of corneal injuries with the maintenance of the power of vision is the main aim of most studies. The current study was conducted to evaluate the effect of hesperidin with or without olive oil after its deposition under the bulbar conjunctiva on the healing of induced alkali burn corneal ulcers. For carrying out the study, 18 New Zealand albino rabbits were included. They were divided into three equal groups. Group I (control) received 0.5 ml of normal saline 0.9% under the bulbar conjunctiva 5 times at one-week intervals. Group II (H) received 0.5 ml of hesperidin nanovesicles subconjunctivally 5 times at one-week intervals. Group III (HO) received 0.5 ml of nanovesicles of hesperidin with olive oil under the bulbar conjunctiva 5 times one week apart. The right eye of animals was subjected to induction of corneal ulcer using 1% NaOH before the commencement of treatment. The left eye was used as a negative control one. The animals were examined clinically (lacrimation, neovascularization, pus formation, corneal perforation, measurement of corneal ulcer), and with fluorescein test staining every week just before each treatment. The animals were examined on days 1, 8, 15, 22, 29, 36 post corneal ulcer induction. At the end of the experiment, the treated and nontreated eye samples were collected for histopathological and electron microscopy examination. The results showed an improvement in the total clinical score in groups H and HO especially in the fifth week, while the control group displayed increasing in the inflammatory process of the injured eye throughout the time of experiment. There was a significant difference between both of H and HO groups and the control group in the third, fourth, and fifth weeks. The results of the histopathological and electron microscopy revealed the superiority of hesperidin with olive oil over hesperidin alone in promoting the healing of corneal ulcers (p= 0.045). The current study concluded that the subconjunctival injection of hesperidin with or without olive oil has a beneficial and promoting effect in the healing and regeneration of alkali burn corneal ulcers in rabbits. Moreover, subconjunctival injections can ensure long-term drug maintenance compared to topical methods, which in turn saves time and effort. [ABSTRACT FROM AUTHOR]

Abstract Background T helper 2 (Th2) cells are thought to play critical roles in allergic conjunctivitis (AC). They release inflammatory cytokines to promote an allergic response in AC. Due to individual heterogeneity and long-term chronic management, current therapies do not always effectively control AC. Mesenchymal stem cells (MSCs) have been shown to be effective in treating allergy-related disorders, but it is unclear how exactly the Th2-mediated allergic response is attenuated. This study aims to elucidate the therapeutic effect and mechanism of the human umbilical cord MSCs (hUCMSCs) in a mouse model of experimental AC (EAC). Methods A mouse EAC model was established by inoculating short ragweed (SRW) pollen. After the SRW pollen challenge, the mice received a single subconjunctival or tail vein injection of 2 × 106 hUCMSCs, or subconjunctival injection of hUCMSCs conditioned medium (hUCMSC-CM), and dexamethasone eye drops was used as positive control; subsequent scratching behavior and clinical symptoms were assessed. Immunostaining and flow cytometry were carried out to show allergic reactions and the activation of CD4 + T cell subsets in the conjunctiva and cervical lymph nodes (CLNs). Gene expression was determined by RNA-seq and further verified by qRT-PCR and Western blot. Co-culture assays were performed to explore the regulatory role of hUCMSCs in the differentiation of CD4 + naive T cells (Th0) into Th2 cells. Results Subconjunctival administration of hUCMSCs resulted in fewer instances of scratching and lower inflammation scores in EAC mice compared to the tail vein delivery, hUCMSC-CM and control groups. Subconjunctival administration of hUCMSCs reduced the number of activated mast cells and infiltrated eosinophils in the conjunctiva, as well as decreased the number of Th2 cells in CLNs. After pretreatment with EAC mouse serum in vitro to mimic the in vivo milieu, hUCMSCs were able to inhibit the differentiation of Th0 into Th2 cells. Further evidence demonstrated that repression of Th2 cell differentiation by hUCMSCs is mediated by CRISPLD2 through downregulation of STAT6 phosphorylation. Additionally, hUMCSCs were able to promote the differentiation of Th0 cells into regulatory T cells in CLNs of EAC mice. Conclusions Subconjunctival injection of hUCMSCs suppressed the Th2-allergic response and alleviated clinical symptoms. This study provides not only a potential therapeutic target for the treatment of AC but also other T cell-mediated diseases.

Background: Diabetic retinopathy (DR) is a vision-threatening complication that affects virtually all diabetic patients. Various treatments have been attempted, but they have many side effects and limitations. Alternatively, stem cell therapy is being actively researched, but it faces challenges due to a low cell survival rate. In this study, stem cells were pretreated with sirolimus, which is known to promote cell differentiation and enhance the survival rate. Additionally, the subconjunctival route was employed to reduce complications following intravitreal injections. Methods: Diabetes mellitus was induced by intraperitoneal injection of 55 mg/kg of streptozotocin (STZ), and DR was confirmed at 10 weeks after DM induction through electroretinogram (ERG). The rats were divided into four groups: intact control group (INT), diabetic retinopathy group (DR), DR group with subconjunctival MSC injection (DR-MSC), and DR group with subconjunctival sirolimus-pretreated MSC injection (DR-MSC-S). The effects of transplantation were evaluated using ERG and histological examinations. Results: The ERG results showed that the DR-MSC-S group did not significantly differ from the INT in b-wave amplitude and exhibited significantly higher values than the DR-MSC and DR groups (p < 0.01). The flicker amplitude results showed that the DR-MSC and DR-MSC-S groups had significantly higher values than the DR group (p < 0.01). Histological examination revealed that the retinal layers were thinner in the DR-induced groups compared to the INT group, with the DR-MSC-S group showing the thickest retinal layers among them. Conclusions: Subconjunctival injection of sirolimus-pretreated MSCs can enhance retinal function and mitigate histological changes in the STZ-induced DR rat model. [ABSTRACT FROM AUTHOR]

AIM: To investigate the effectiveness and safety of subconjunctival injection of conbercept in the treatment of corneal neovascularization (CNV). METHODS: The data on 10 consecutively recruited patients with CNV who received a subconjunctival conbercept (1 mg) once, and measured the area, length, and diameter of neovascularization before and after (1d, 1, 2wk, and 1mo) treatment as well as the occurrence of systemic and ocular complications after treatment were analyzed. RESULTS: There was a statistically significant reduction in the area of CNV one day after treatment (mean±SD: 38.46±11.36 mm2), compared with before treatment (42.46±12.80 mm2, P

Diabetic retinopathy (DR) is a microvascular complication associated with vascular endothelial growth factor (VEGF) overexpression. Therapeutic delivery to the retina is a challenging phenomenon due to ocular biological barriers. Sorafenib tosylate (ST) is a lipophilic drug with low molecular weight, making it ineffective at bypassing the blood–retinal barrier (BRB) to reach the target site. Cubosomes are potential nanocarriers for encapsulating and releasing such drugs in a sustained manner. The present research aimed to compare the effects of sorafenib-tosylate-loaded cubosome nanocarriers (ST-CUBs) and a sorafenib tosylate suspension (ST-Suspension) via subconjunctival route in an experimental DR model. In this research, ST-CUBs were prepared using the melt dispersion emulsification technique. The distribution of prepared nanoparticles into the posterior eye segments was studied with confocal microscopy. The ST-CUBs were introduced into rats' left eye via subconjunctival injection (SCJ) and compared with ST-Suspension to estimate the single-dose pharmacokinetic profile. Streptozotocin (STZ)-induced diabetic albino rats were treated with ST-CUBs and ST-Suspension through the SCJ route once a week for 28 days to measure the inhibitory effect of ST on the diabetic retina using histopathology and immunohistochemistry (IHC) examinations. Confocal microscopy and pharmacokinetic studies showed an improved concentration of ST from ST-CUBs in the retina. In the DR model, ST-CUB treatment using the SCJ route exhibited decreased expression levels of VEGF, pro-inflammatory cytokines, and adhesion molecules compared to ST-Suspension. From the noted research findings, it was concluded that the CUBs potentially enhanced the ST bioavailability. The study outcomes established that the developed nanocarriers were ideal for delivering the ST-CUBs via the SCJ route to target the retina for facilitated DR management. [ABSTRACT FROM AUTHOR]

Background: T helper 2 (Th2) cells are thought to play critical roles in allergic conjunctivitis (AC). They release inflammatory cytokines to promote an allergic response in AC. Due to individual heterogeneity and long-term chronic management, current therapies do not always effectively control AC. Mesenchymal stem cells (MSCs) have been shown to be effective in treating allergy-related disorders, but it is unclear how exactly the Th2-mediated allergic response is attenuated. This study aims to elucidate the therapeutic effect and mechanism of the human umbilical cord MSCs (hUCMSCs) in a mouse model of experimental AC (EAC). Methods: A mouse EAC model was established by inoculating short ragweed (SRW) pollen. After the SRW pollen challenge, the mice received a single subconjunctival or tail vein injection of 2 × 106 hUCMSCs, or subconjunctival injection of hUCMSCs conditioned medium (hUCMSC-CM), and dexamethasone eye drops was used as positive control; subsequent scratching behavior and clinical symptoms were assessed. Immunostaining and flow cytometry were carried out to show allergic reactions and the activation of CD4 + T cell subsets in the conjunctiva and cervical lymph nodes (CLNs). Gene expression was determined by RNA-seq and further verified by qRT-PCR and Western blot. Co-culture assays were performed to explore the regulatory role of hUCMSCs in the differentiation of CD4 + naive T cells (Th0) into Th2 cells. Results: Subconjunctival administration of hUCMSCs resulted in fewer instances of scratching and lower inflammation scores in EAC mice compared to the tail vein delivery, hUCMSC-CM and control groups. Subconjunctival administration of hUCMSCs reduced the number of activated mast cells and infiltrated eosinophils in the conjunctiva, as well as decreased the number of Th2 cells in CLNs. After pretreatment with EAC mouse serum in vitro to mimic the in vivo milieu, hUCMSCs were able to inhibit the differentiation of Th0 into Th2 cells. Further evidence demonstrated that repression of Th2 cell differentiation by hUCMSCs is mediated by CRISPLD2 through downregulation of STAT6 phosphorylation. Additionally, hUMCSCs were able to promote the differentiation of Th0 cells into regulatory T cells in CLNs of EAC mice. Conclusions: Subconjunctival injection of hUCMSCs suppressed the Th2-allergic response and alleviated clinical symptoms. This study provides not only a potential therapeutic target for the treatment of AC but also other T cell-mediated diseases. [ABSTRACT FROM AUTHOR]

AIM: To systematically evaluate the effectiveness and safety of subconjunctival and intravitreal injection of triamcinolone acetonide(TA)in the treatment of macular edema secondary to non-infectious uveitis.METHODS: Databases, including Wanfang database, CNKI, VIP database, CBM, PubMed, Embase, Cochrane Library and Web of Science, were searched from the establishment to May 2022. A clinical randomized controlled trial(RCT)of TA for the treatment of non-infectious uveitis secondary to macular edema was included, with subconjunctival injection of TA in the trial group and intravitreal injection of triamcinolone acetonide(IVTA)in the control group. Review Manager 5.4 and Stata15 were used for Meta-analysis of the postoperative best corrected visual acuity(BCVA), central macular thickness(CMT), overall efficiency and adverse effects. Odds ratio(OR), weighted mean(MD)and 95% confidence interval(CI)were applied to evaluate.RESULTS: A total of 8 studies were included. The Meta-analysis showed that subconjunctival injection of TA was better than the IVTA group in improving BCVA(MD=0.81, 95%CI: 0.60～1.01, P

Background: Recurrence, which is indicated by the expansion of fibrovascular tissue past the limbus and onto the cornea, is the main worry in pterygium surgery. Several techniques have been put forth to slow the pace of recurrence. Pterygium recurrences typically occur within the first three months following surgery. Objective: To evaluate the efficacy of a protocol based on applying two 2.5 mg/ml bevacizumab injections, before and after surgery, as adjuvant therapy of surgical pterygium excision to assess its role in preventing the recurrence of pterygium. Patients and Methods: A randomized control study was conducted on 84 patients. Complete ophthalmic examinations were performed on all patients, including the following: history, visual acuity, slit lamp examination, intraocular pressure (IOP) measurement, fundus examination, and Refraction by Auto refractometer. Results: The recurrence rate was significantly lower in the group that underwent pre- and postoperative bevacizumab injection. Moreover, we observed improvements in dimensions and vascularization of pterygium one week after the first subconjunctival injection. In our study, there were some postoperative complications; most of them in the pretreated group were related to pterygium surgery, such as subconjunctival hemorrhage, photophobia, and conjunctival injection. All of these complications occurred in both groups, but with the use of bevacizumab the field was less vascular, and the subconjunctival hemorrhage was less remarkable in the pretreated group than in the control group. Conclusion: Dimensions and vascularization of pterygium significantly decreased one week after the first subconjunctival bevacizumab injection. The recurrence rate was significantly decreased in the group that underwent pre- and postoperative bevacizumab injection. [ABSTRACT FROM AUTHOR]

Background: Diabetic retinopathy (DR) is a vision-threatening complication that affects virtually all diabetic patients. Various treatments have been attempted, but they have many side effects and limitations. Alternatively, stem cell therapy is being actively researched, but it faces challenges due to a low cell survival rate. In this study, stem cells were pretreated with sirolimus, which is known to promote cell differentiation and enhance the survival rate. Additionally, the subconjunctival route was employed to reduce complications following intravitreal injections. Methods: Diabetes mellitus was induced by intraperitoneal injection of 55 mg/kg of streptozotocin (STZ), and DR was confirmed at 10 weeks after DM induction through electroretinogram (ERG). The rats were divided into four groups: intact control group (INT), diabetic retinopathy group (DR), DR group with subconjunctival MSC injection (DR-MSC), and DR group with subconjunctival sirolimus-pretreated MSC injection (DR-MSC-S). The effects of transplantation were evaluated using ERG and histological examinations. Results: The ERG results showed that the DR-MSC-S group did not significantly differ from the INT in b-wave amplitude and exhibited significantly higher values than the DR-MSC and DR groups (p < 0.01). The flicker amplitude results showed that the DR-MSC and DR-MSC-S groups had significantly higher values than the DR group (p < 0.01). Histological examination revealed that the retinal layers were thinner in the DR-induced groups compared to the INT group, with the DR-MSC-S group showing the thickest retinal layers among them. Conclusions: Subconjunctival injection of sirolimus-pretreated MSCs can enhance retinal function and mitigate histological changes in the STZ-induced DR rat model.

Purpose: To describe a novel approach of subconjunctival injection of mitomycin C (MMC) at the end of trabeculectomy and compare it with intraTenon MMC injection.Methods: This pilot study included 40 eyes of 40 patients with uncontrolled primary and secondary glaucoma. Patients below18 years and failed trabeculectomy were excluded. Patients were randomly allocated into groups A and B (20 patients each). Group A patients received subconjunctival MMC injection in the superonasal quadrant at the end of standard trabeculectomy. Group B received an intraTenon MMC injection before the initial conjunctival incision. Outcome measures included intra-ocular pressure (IOP) reduction, bleb morphology, and complication rates. The complete success was defined as an IOP of ≤21 mmHg without antiglaucoma drugs.Results: The mean preoperative IOP of 46.00 ± 11.2 mmHg in group A and 43.05 ± 10.3 mmHg in group B reduced to 12.00 ± 2.41 mmHg (P ≤ 0.001) in group A and 13.65 ± 2.76 mmHg in group B (P ≤ 0.001) at last follow-up. Complete success was 95% and 75% in groups A and B, respectively, 19 months after surgery. Avascular microcystic blebs (70% of group A and 45% of group B) were more common than avascular white blebs (15% in group A and 35% in group B). No intraoperative complications were seen. Postoperative wound leak, hypotony, choroidal detachment, or endophthalmitis were not encountered in any group.Conclusion: A novel approach of subconjunctival MMC application during trabeculectomy is reported. Both approaches appear to be highly effective in reducing IOP in primary and secondary glaucoma with similar safety profiles and bleb morphology. Subconjunctival MMC yielded a greater success rate (95%) compared to the intraTenon MMC group (75%). [ABSTRACT FROM AUTHOR]

Background/aim: Diabetic retinopathy (DR), a complication of diabetes, causes damage to retinal blood vessels and can lead to vision impairment. Persistent high blood glucose levels contribute to this damage, and despite ongoing research, effective treatment options for DR remain limited. Dimethyl sulfoxide (DMSO) has shown anti-inflammatory and antioxidant properties in both in vivo and in vitro studies; however, its potential as an anti-inflammatory agent in the context of DR has not yet been explored. This study aimed to assess the effects of subconjunctival injection of DMSO on the progression of DR., Materials and Methods: DR was induced in rats using intraperitoneal injections of streptozotocin (55 mg/kg), confirmed by measuring blood glucose levels and electroretinography (ERG). The rats were divided into five groups: a normal control group (CON), a DR control group receiving PBS injections (DMSO 0), and three DR groups receiving different concentrations of DMSO (98%, 50%, and 10%). Retinal function was evaluated using ERG at weeks 10 and 14, and histological analysis at week 16., Results: The DMSO 50 group had significantly higher B-wave amplitude in ERG compared to the DMSO 0 group (p<0.05). Flicker response amplitudes were also significantly greater in the DMSO 50 and DMSO 10 groups compared to DMSO 0 (p<0.05). Histological examination revealed thinner retinal layers in the DMSO 0 group compared to the CON group, while the DMSO-treated groups showed improved retinal thickness., Conclusion: Subconjunctival injection of 50% DMSO appears to improve retinal function in a rat model of DR., (Copyright © 2025, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

الملخص: أهداف البحث: الظفرة هي كتلة العين الخارجية الليفية الوعائية التي تنمو من الملتحمة إلى القرنية. لم يتم التحقيق في تأثير الحقن تحت الملتحمة لتريامسينولون وبيفاسيزوماب بشكل كاف في جميع أنحاء العالم. تهدف هذه الدراسة إلى تحليل تعبير انترلوكين-١ بعد حقن تريامسينولون بيفاسيزوماب تحت الملتحمة. طرق البحث: تم تقسيم جميع المرضى بصورة عشوائية إلى ثلاث مجموعات. كل ٥ عيون في مجموعة تريامسينولون ومجموعة بيفاسيزوماب ومجموعة الدواء الوهمي. تم حقن جميع الأشخاص تحت الملتحمة قبل أسبوع واحد من الجراحة، ثم أجريت الجراحة بتقنية الطعم الذاتي. تضمنت مقاييس النتائج الرئيسية تغييرات في تعبير انترلوكين-١ حمض ريبونيوكليك المرسال بين مجموعة تريامسينولون، بيفاسيزوماب، ومجموعات الدواء الوهمي. النتائج: تم الانتهاء من جميع العينات بعد شهر واحد من المتابعة. كانت التغيرات في مستويات الدم لتعبير انترلوكين-١ حمض ريبونيوكليك المرسال في مجموعة بيفاسيزوماب ٤.٨١ ± ٠.٥٢، وكانت مجموعة تريامسينولون ٣.٤٠ ± ٢.٦٣، وكانت مجموعة الدواء الوهمي ١.٠٨± ١.٤٨، على التوالي. في المقارنة بين المجموعات، كان هناك تأثير معنوي بين مجموعة بيفاسيزوماب ومجموعة الدواء الوهمي، ٣.٧٣ ± ١.١٢، مع عدم وجود تأثير معنوي في مجموعة تريامسينولون، ١.٤٠± ١.١٢. الاستنتاجات: كان الحقن تحت الملتحمة بيفاسيزوماب وتريامسينولون قبل الجراحة فعالا في قمع الالتهاب في الظفرة. Abstract: Objectives: Pterygium is a fibrovascular external ocular mass that grows from the conjunctiva into the cornea. The effect of subconjunctival injection of triamcinolone and bevacizumab has been inadequately investigated worldwide. This study aims to analyse the expression of IL-1 after the injection of triamcinolone and bevacizumab subconjunctiva. Methods: All patients are randomized into three groups: the triamcinolone, bevacizumab group, and placebo groups, with 5 patients in each in group. All subjects are injected subconjunctivally one week before surgery, and then surgery is performed with the autograft technique. The main outcome measures include changes in the IL-1 mRNA expression between the triamcinolone, bevacizumab, and placebo groups. Results: All samples are completed after one month of follow-up. The changes in blood levels of mRNA IL-1 expression are as follows: 4.81 ± 0.52 in the bevacizumab group, 3.40 ± 2.63 in the triamcinolone group, and 1.08 ± 1.48 in the placebo group (p = 0.04). In the comparison between groups, there is a significant effect between the bevacizumab and placebo groups, 3.73 ± 1.12 (p = 0.00), with no significant effect in the triamcinolone group, 1.40 ± 1.12 (p = 0.06). Conclusion: The subconjunctival injection of bevacizumab and triamcinolone before surgery is effective in suppressing inflammation in pterygium.

AIM: To evaluate the clinical effects of subconjunctival injection of vitamin C in the treatment of corneal ulcer by using Meta-analysis.METHODS: Using “vitamin C” and “corneal ulcer” as keywords, the randomized controlled trials(RCT)of subconjunctival injection of vitamin C in Embase, Cochrane library, Pubmed, CNKI and Wanfang database in the treatment of corneal ulcer was searched. Relevant reference published before February 2021. The risk bias tool provided by the Cochrane cooperation scale was used to assess the risk bias of included studies of RCTs. The publication bias of the included studies were assessed by the Egger's test with Stata software. Meta-analysis was performed with RevMan 5.3.RESULTS: A total of 32 eligible articles were included, all of which were Chinese literatures, with a total of 4 514 patients. The control group was treated with routine treatment, and the experimental group was treated with subconjunctival injection of vitamin C combined with routine treatment. The Meta-analysis showed that the experimental group was better than control group(OR=4.61, 95%CI:3.70, 5.74). The recurrence rate was lower than control group(OR=0.24, 95%CI: 0.18, 0.31). The cure time in experimental group was shorter than control group(MD= -6.29, 95%CI: -7.08, -5.51), 32 studies do not adequately report adverse drug reactions(ADR). Egger's test was performed on the total effective rate, recurrence rate and cure time. The results showed that there was publication bias in the total effective rate and cure time. Trim and fill method showed that the publication bias did not affect the results.CONCLUSION: Subconjunctival injection of vitamin C is feasible in the treatment of corneal ulcer. The clinical effect, cure time and recurrence rate were better than routine treatment. However, due to the low intensity of the included research evidence, more multicenter, randomized double-blind clinical trials are needed to improve the evidence intensity of vitamin C in the treatment of corneal ulcer.

Posterior eye diseases, such as age-related macular degeneration and diabetic retinopathy, are difficult to treat due to ineffective drug delivery to affected areas. Intravitreal injection is the primary method for posterior eye drug delivery; however, it is usually accompanied by complications. Therefore, an effective and non-invasive method is required. Self-assembling nanoparticles (NPs) made from gelatin-epigallocatechin gallate (EGCG) were synthesized (GE) and surface-decorated with hyaluronic acid (HA) for drug delivery to the retinal/choroidal area. Different HA concentrations were used to prepare NPs with negative (GEH−) or positive (GEH+) surface charges. The size/zeta potential and morphology of the NPs were characterized by a dynamic light scattering (DLS) system and transmission electron microscope (TEM). The size/zeta potential of GEH+ NPs was 253.4 nm and 9.2 mV. The GEH− NPs were 390.0 nm and −35.9 mV, respectively. The cytotoxicity was tested by adult human retinal pigment epithelial cells (ARPE-19), with the results revealing that variant NPs were non-toxicity at 0.2–50 µg/mL of EGCG, and that the highest amount of GEH+ NPs was accumulated in cells examined by flowcytometry. Topical delivery (eye drops) and subconjunctival injection (SCI) methods were used to evaluate the efficiency of NP delivery to the posterior eyes in a mouse model. Whole eyeball cryosections were used to trace the location of fluorescent NPs in the eyes. The area of fluorescent signal obtained in the posterior eyes treated with GEH+ NPs in both methods (eye drops: 6.89% and SCI: 14.55%) was the greatest when compared with other groups, especially higher than free dye solution (2.79%). In summary, GEH+ NPs can be transported to the retina by eye drops and SCI; in particular, eye drops are a noninvasive method. Furthermore, GEH+ NPs, characterized by a positive surface and HA decoration, could facilitate drug delivery to the posterior eye as a useful drug carrier. [ABSTRACT FROM AUTHOR]

Abstract Mesenchymal stem cells (MSCs) have unique and beneficial properties and are currently used to treat a broad variety of diseases. These properties include the potential for differentiation into other cell types, secretion of different trophic factors that promote a regenerative microenvironment, anti-inflammatory actions, selective migration to damaged tissues, and non-immunogenicity. MSCs are effective for the treatment of ocular surface diseases such as dry eye, corneal burns, and limbal stem cell deficiency (LSCD), both in experimental models and in humans. LSCD is a pathological condition in which damage occurs to the limbal epithelial stem cells, or their niche, that are responsible for the continuous regeneration of the corneal epithelium. If LSCD is extensive and/or severe, it usually causes corneal epithelial defects, ulceration, and conjunctival overgrowth of the cornea. These changes can result in neovascularization and corneal opacity, severe inflammation, pain, and visual loss. The effectiveness of MSCs to reduce corneal opacity, neovascularization, and inflammation has been widely studied in different experimental models of LSCD and in some clinical trials; however, the methodological disparity used in the different studies makes it hard to compare outcomes among them. In this regard, the MSC route of administration used to treat LSCD and other ocular surface diseases is an important factor. It should be efficient, minimally invasive, and safe. So far, intravenous and intraperitoneal injections, topical administration, and MSC transplantation using carrier substrata like amniotic membrane (AM), fibrin, or synthetic biopolymers have been the most commonly used administration routes in experimental models. However, systemic administration carries the risk of potential side effects and transplantation requires surgical procedures that could complicate the process. Alternatively, subconjunctival injection is a minimally invasive and straightforward technique frequently used in ophthalmology. It enables performance of local treatments using high cell doses. In this review, we provide an overview of the current status of MSC administration by subconjunctival injection, analyzing the convenience, safety, and efficacy for treatment of corneal failure due to LSCD in different experimental models. We also provide a summary of the clinical trials that have been completed, are in progress, or being planned.

Yuzhao Sun, Rui Hua Department of Ophthalmology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, People’s Republic of ChinaCorrespondence: Rui HuaDepartment of Ophthalmology, The First Affiliated Hospital of China Medical University, No. 155 Nanjingbei Street, Heping District, Shenyang, Liaoning 110001, People’s Republic of ChinaTel +86-13-840583355Fax +86-24-83282630Email woodshua@126.comPurpose: To investigate the effectiveness and safety of subconjunctival/perilesional 5-fluorouracil injections on ocular surface squamous neoplasia (OSSN) during a 3-year follow-up period.Patients and Methods: We followed up six patients with intraepithelial OSSN (in one eye each) that had regressed after subconjunctival/perilesional 5-fluorouracil injections. Conjunctival fluorescein angiography (FA) and indocyanine green angiography (ICGA), as well as anterior segment optical coherence tomography (AS-OCT), were performed to evaluate the OSSN status 3 years after initiation of treatment.Results: The mean age of patients (five males, one female) at baseline was 62.3± 11.6 years. The mean number of 5-fluorouracil injections was 17.0± 8.6, with a mean treatment duration of 13.0± 7.4 weeks. At the final visit, both intratumoral and conjunctival feeding vessels had disappeared on ICGA and FA, with no neovascularization-related leakage, in accordance with the results of AS-OCT. The period from complete tumor regression to final visit according to AS-OCT was 32.5± 4.2 months, which was longer than that according to ICGA (31.3± 3.2 months, p=0.034). The final best-corrected visual acuity was similar to that at baseline (p=0.128). No side effects were observed in any of the eyes.Conclusion: Subconjunctival/perilesional 5-fluorouracil injections are an effective and safe treatment for OSSN. Future studies with a larger sample size are warranted for confirmation of our findings, as well as investigation into the reasons for residual areas of non-perfusion in the conjunctiva.Keywords: ocular surface squamous neoplasia, subconjunctival injection, 5-fluorouracil, long-term follow-up, conjunctival angiography, optical coherence tomography

AIM: To evaluate the efficacy and safety of subconjunctival triamcinolone acetonide (TA) injections for treating uveitic macular edema (UME). METHODS: This retrospective case series study included patients with UME who received subconjunctival TA injections with a minimum follow-up period of 6mo. The main outcome measure was central macular thickness (CMT). The secondary outcome measures included best-corrected visual acuity (BCVA), recurrence rate and intraocular pressure (IOP). RESULTS: In total, 65 patients (80 eyes), mainly including idiopathic uveitis in 33 patients (50.77%) and Vogt-Koyanagi-Harada (VKH) syndrome in 19 patients (29.23%), were enrolled in this study. The mean CMT decreased from 457.6±173.0 μm at baseline to 325.9±176.8, 302.7±148.2, 332.2±177.3 and 270.6±121.6 μm at 1-, 2-, 3- and 6-months postinjection, respectively (all P

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Purpose: To investigate the effects of subconjunctival bevacizumab, ranibizumab, and aflibercept in an experimental corneal neovascularization model. Materials and methods: The eyes of 24 rats were chemically cauterized and randomly divided into four groups: bevacizumab group (0.05 mL/1.25 mg bevacizumab), ranibizumab group (0.05 mL/0.5 mg ranibizumab), aflibercept group (0.05 mL/1.25 mg aflibercept), and control group (0.05 mL saline solution). Plasma vascular endothelial growth factor (VEGF) levels were among the major measurement outcomes to assess corneal neovascularization. The collected plasmas were analyzed using the SIGMA RAB0511 Rat VEGF Elisa kit. The PCR technique and VEGF amplification procedures were used for molecular analysis. Each cornea was removed and histologically examined on day 21. Corneal images were evaluated by image analyzer software. Results: In the post-injection period, the number of major corneal arteries decreased significantly in the injection groups when compared to the control group (p = 0.037), but no statistically significant differences were noted among the injection groups (p > 0.05). The aflibercept group had the lowest area of neovascularization. Immunohistochemical staining revealed substantially lower VEGF percentages in neovascularized arteries of the injection groups than the control group (p = 0.015). In TUNEL staining, the mean TUNEL value (number/1hpf) was substantially greater in the control group than in the injection groups, but the mean TUNEL values were similar between the injection groups (p = 0.019, p > 0.05, respectively). No statistically significant differences were observed between the groups in terms of corneal surface area with increased cellularity, edema, and inflammation (p = 0.263). The mean plasma VEGF concentration in the control group was statistically greater than those in the injection groups (p = 0.001). Conclusion: Subconjunctival bevacizumab, ranibizumab, and aflibercept crossed the blood and seemed to be effective in inhibiting corneal neovascularization without causing epitheliopathy in an experimental rat model compared to the controls. However, no significant results were noted between these three anti-VEGF molecules. [ABSTRACT FROM AUTHOR]

Nitrogen mustard (NM) is a potent vesicating chemical warfare agent that is primarily absorbed through skin, inhalation, or ocular surface. Ocular exposure of NM can cause acute to chronic keratopathy which can eventually lead to blindness. There is a current lack of effective countermeasures against ocular exposure of NM despite their imperative need. Herein, we aim to explore the sustained effect of Dexamethasone sodium phosphate (DSP)-loaded polymeric nanoparticles (PLGA-DSP-NP) following a single subconjunctival injection in the management and prevention of corneal injury progression upon exposure to NM. DSP is an FDA approved corticosteroid with proven anti-inflammatory properties. We formulated PLGA-DSP-NP with zinc chelation ion bridging method using PLGA polymer, with particles of approximately 250 nm and a drug loading of 6.5 wt%. Under in vitro sink conditions, PLGA-DSP-NP exhibited a sustained drug release for two weeks. Notably, in NM injured cornea, a single subconjunctival (SCT) injection of PLGA-DSP-NP outperformed DSP eyedrops (0.1%), DSP solution, placebo NP, and saline, significantly mitigating corneal neovascularization, ulceration, and opacity for the two weeks study period. Through PLGA-DSP-NP injection, sustained DSP release hindered inflammatory cytokine recruitment, angiogenic factors, and endothelial cell proliferation in the cornea. This strategy presents a promising localized corticosteroid delivery system to effectively combat NM-induced corneal injury, offering insights into managing vesicant exposure. [Display omitted] • Nitrogen mustard exposure causes corneal ulceration, opacity, and neovascularization. • Nitrogen mustard exposure upregulates multiple inflammatory and angiogenic cytokines in the cornea. • A single subconjunctival (SCT) injection of PLGA-DSP-NP prevents the progression of NM-induced corneal injury. [ABSTRACT FROM AUTHOR]

Rat limbal niche cells (LNCs) have been proven to induce transdifferentiation of oral mucosal epithelial cells (OMECs) into corneal epithelial-like cells termed transdifferentiated oral mucosal epithelial cells (T-OMECs). This investigation aimed to evaluate the effect of subconjunctival T-OMEC injections on alkali-induced limbal stem cell deficiency (LSCD) in rats. LNCs were cocultured with OMECs in the Transwell system to obtain T-OMECs, with NIH-3T3 cells serving as a control. Subconjunctival injection of single T-OMEC or OMEC suspension was performed immediately after corneal alkali injury. T-OMECs were prelabeled with the fluorescent dye CM-DiI in vitro and tracked in vivo. Corneal epithelial defect, opacity, and neovascularization were quantitatively analyzed. The degree of corneal epithelial defect (from day 1 onward), opacity (from day 5 onward), and neovascularization (from day 2 onward) was significantly less in the T-OMEC group than in the OMEC group. Cytokeratin 12 (CK12), pigment epithelium–derived factor, and soluble fms-like tyrosine kinase-1 were expressed at a higher rate following T-OMEC injection. Some CM-DiI-labeled cells were found to be coexpressed with CK12, Pax6, and ΔNp63α in the corneal epithelium after subconjunctival injection. Subconjunctival injection of T-OMECs prevents conjunctival invasion and maintains a normal corneal phenotype, which might be a novel strategy in the treatment of LSCD: [ABSTRACT FROM AUTHOR]

Aims: To compare the long-term safety and efficacy of subconjunctival injection mitomycin C(MMC) with conventional sponge applied MMC during trabeculectomy., Methods and Material: Retrospective analysis of 98 eyes of 90 patients who underwent trabeculectomy with Mitomycin C were divided into two groups, group 1- sponge (n = 52) and group 2- Injection(n = 46). Follow-up data were collected on day one, day 15, one month, three months, six months, one year, two years and three years. Data from baseline and follow-up visits were analyzed and compared to study the significant difference in intraocular pressure (IOP), number of antiglaucoma medications (AGM) and best corrected visual acuity (BCVA) . P -value of <0.05 was considered statistically significant., Results: Mean preop IOP was 34.61 ± 13.3 mmHg in group one and 33.07 ± 9.6 mmHg in group two, which reduced to 11.43 ± 3.2 and 11.59 ± 3.2 mmHg at three years ( p  < 0.001 in both groups) with no significant difference between the groups. Mean number of preoperative AGM was 2.28 ± 0.8 and 2.42 ± 0.7 in group one and two respectively which reduced to 1.19 ± 1.1( p  = 0.405) and 0.88 ± 0.9( p  = 0.001) at three years. Complete and overall success rates (complete + qualified) were 59.3% and 78.9% in group one and 60.9% and 80.4% in group two at three years. No statistically significant difference was found in complication rates, post-operative interventions, and final visual outcome in both groups., Conclusions: Subconjunctival Injection MMC was a safe and effective alternative to sponge application with comparable long term surgical outcomes., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Corneal neovascularization (CNV) is one of the major causes of severe disorders in ocular surface. Subconjunctival administration provides a localized and effective delivery of anti-angiogenic agents to inhibit neovascularization. In the present study, the ABA triblock copolymer of poly(D,L-lactic-co-glycolic acid)-block-poly(ethylene glycol)-block-poly(D,L-lactic-co-glycolic acid) (PLGA-PEG-PLGA) was used as a sustained drug delivery carrier for metformin (MET) and levofloxacin hydrochloride (LFH). Both drugs and PLGA-PEG-PLGA copolymers could be easily dissolved in water at low or room temperature and the mixed solution could form a drug-loaded thermosensitive hydrogel in terms of body temperature response. The in vitro release investigation displayed a sustained release of MET and LFH from the formulation for one month. The in vivo efficacy of subconjunctival injection of the MET + LFH loaded thermosensitive hydrogel in inhibiting CNV was evaluated on a mouse model of corneal alkali burn. Compared with the single administration of MET or LFH loaded thermosensitive hydrogel, the MET + LFH loaded thermosensitive hydrogel remarkably inhibited the formation of CNV. The sustained release of MET and an antibiotic (LFH) provides synergistic therapeutic outcome. As a result, the co-delivery of MET and LFH using PLGA-PEG-PLGA thermosensitive hydrogel by subconjunctival injection has great potential for ocular anti-angiogenic therapy.

Xianfang Rong,1–5 Yinghong Ji,1–5 Xiangjia Zhu,1–5 Jin Yang,1–5 Dongjin Qian,1–5 Xiaofen Mo,1–5 Yi Lu1–5 1Department of Ophthalmology and The Eye Institute, Eye and Ear, Nose, and Throat Hospital, Fudan University, Shanghai, China; 2The Key Laboratory of Myopia, Ministry of Health, Shanghai, China; 3Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China; 4Key National Health Committee Key Laboratory of Myopia, Fudan University, Shanghai, China; 5Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China Background: To pursuit effective sustained release systems for insulin to treat diabetic retinopathy (DR), a novel insulin delivering system was developed via loading onto chitosan nanoparticles/poly(lactic-co-glycolic acid)-poly(ethylene glycol)-poly(lactic-co-glycolic acid) hydrogel (ICNPH). Methods and materials: Examinations including electroretinography, HE staining, transmission electron microscopy, terminal deoxynucleotidyl transferased UTP nick-end labeling, immunofluorescence, Western blot, and real-time polymerase chain reaction were performed to evaluate the neuroprotective efficacy of ICNPH on DR by a single subconjunctival injection. Results: Compared with the insulin, blank, and sham treatment groups, subconjunctival injection of ICNPH significantly reduced the decrease of scotopic B-wave amplitude, alleviated retinal micro- and ultrastructural changes, and reduced retinal cell apoptosis caused in DR rats. Meanwhile, a significant reduction of vascular endothelial growth factor and glial fibrillary acidic protein expression as well as a remarkable increase in Occludin expression was also found in retinas in ICNPH group compared with the sham treatment group. Conclusion: The results indicate that ICNPH has sufficient neuroprotective effect on retinas through subconjunctival injection in DR rats and facilitates controlled insulin delivery. It might be one of the therapeutic strategies for DR in the near future. Keywords: ICNPH, diabetic retinopathy, subconjunctival injection, insulin delivery, thermosensitive hydrogel, PLGA-PEG-PLGA hydrogel

Mesenchymal stem cells (MSCs) have unique and beneficial properties and are currently used to treat a broad variety of diseases. These properties include the potential for differentiation into other cell types, secretion of different trophic factors that promote a regenerative microenvironment, anti-inflammatory actions, selective migration to damaged tissues, and non-immunogenicity. MSCs are effective for the treatment of ocular surface diseases such as dry eye, corneal burns, and limbal stem cell deficiency (LSCD), both in experimental models and in humans. LSCD is a pathological condition in which damage occurs to the limbal epithelial stem cells, or their niche, that are responsible for the continuous regeneration of the corneal epithelium. If LSCD is extensive and/or severe, it usually causes corneal epithelial defects, ulceration, and conjunctival overgrowth of the cornea. These changes can result in neovascularization and corneal opacity, severe inflammation, pain, and visual loss. The effectiveness of MSCs to reduce corneal opacity, neovascularization, and inflammation has been widely studied in different experimental models of LSCD and in some clinical trials; however, the methodological disparity used in the different studies makes it hard to compare outcomes among them. In this regard, the MSC route of administration used to treat LSCD and other ocular surface diseases is an important factor. It should be efficient, minimally invasive, and safe. So far, intravenous and intraperitoneal injections, topical administration, and MSC transplantation using carrier substrata like amniotic membrane (AM), fibrin, or synthetic biopolymers have been the most commonly used administration routes in experimental models. However, systemic administration carries the risk of potential side effects and transplantation requires surgical procedures that could complicate the process. Alternatively, subconjunctival injection is a minimally invasive and straightforward technique frequently used in ophthalmology. It enables performance of local treatments using high cell doses. In this review, we provide an overview of the current status of MSC administration by subconjunctival injection, analyzing the convenience, safety, and efficacy for treatment of corneal failure due to LSCD in different experimental models. We also provide a summary of the clinical trials that have been completed, are in progress, or being planned. [ABSTRACT FROM AUTHOR]

Corneal neovascularization (NV) predisposes patients to compromised corneal transparency and visional acuity. Sunitinib malate (Sunb-malate) targeting against multiple receptor tyrosine kinases, exerts potent antiangiogenesis. However, the rapid clearance of Sunb-malate eye drops administered through topical instillation limits its therapeutic efficacy and poses a challenge for potential patient compliance. Sunb-malate, the water-soluble form of sunitinib, was shown to have higher intraocular penetration through transscleral diffusion following subconjunctival (SCT) injection in comparison to its sunitinib free base formulation. However, it is difficult to load highly water-soluble drugs and achieve sustained drug release. We developed Sunb-malate loaded poly(D,L-lactic- co -glycolic acid) (PLGA) microspheres (Sunb-malate MS) with a particle size of approximately 15 μm and a drug loading of 7 wt%. Sunb-malate MS sustained the drug release for 30 days under the in vitro infinite sink condition. Subconjunctival (SCT) injection of Sunb-malate MS provided a prolonged ocular drug retention and did not cause ocular toxicity at a dose of 150 μg of active agent. Sunb-malate MS following SCT injection more effectively suppressed the suture-induced corneal NV than either Sunb-malate free drug or the placebo MS. Local sustained release of Sunb-malate through the SCT injection of Sunb-malate MS mitigated the proliferation of vascular endothelial cells and the recruitment of mural cells into the cornea. Moreover, the gene upregulation of proangiogenic factors induced by the pathological process was greatly neutralized by SCT injection of Sunb-malate MS. Our findings provide a sustained release platform for local delivery of tyrosine kinase inhibitors to treat corneal NV. Unlabelled Image [ABSTRACT FROM AUTHOR]

A neurodegenerative disorder, glaucoma is a leading cause of blindness in the world. The conventional treatment strategies do not allow the significant penetration of the drug in the cornea. Therefore, we prepare a brinzolamide (Brz) loaded core-shell nanoparticles (NPs) to enhance the coronial penetration of the drug and thus treating the glaucoma. The shell of the NPs was composed of phosphatidylserine (PS; 1,2-diacyl-sn-glycero-3-phospho-L-serine), whereas the core of the NPs contains the Brz encapsulated in brinzolamide–phosphatidylserine–polymer poly-(DL-lactic acid-co-glycolic acid)–phosphatidylserine (Brz-PS-PLGA). The synthesis of Brz-PS-PLGA was achieved by using a coaxial electrospray process (CEP), which allows the preparation of the particles in a single step. The size of Brz-PS-PLGA with PS shell and brinzolamide–poly (lactic-co-glycolic) acid (Brz-PLGA) without shell was 571 ± 27.02 nm and 456 ± 19.17 nm, respectively. The charges on the surface of Brz-PS-PLGA and Brz-PLGA were (-) 27.45 ± 2.98 mV and (-) 19.47 ± 2.83 mV. The transmission electron microscopy images clearly reveal the PS shell as a light black layer over the dark black PLGA core. The CEP allows the high encapsulation of Brz in Brz-PS-PLGA where percentage of entrapment efficiency for Brz-PS-PLGA was 88.13 ± 6.43%. The release study conducted in a simulated tear fluid revealed the sustained release patterns of Brz from Brz-PS-PLGA and these were nontoxic to the cells as revealed by the cytotoxicity studies. Further, the Brz-PS-PLGA enhanced the coronial penetration of Brz and was capable of significantly reducing the intraocular pressure (IOP) after administration to the rabbit eye in comparison to the Brz-PLGA and free Brz. The results clearly suggest that the PS coating significantly enhances the capability of the particles in reducing IOP. [ABSTRACT FROM AUTHOR]

[Display omitted] Neovascularization contributes to various posterior eye segment diseases such as age-related macular degeneration and diabetic retinopathy. RNA nanoparticles were demonstrated previously to enter the corneal and retinal cells after subconjunctival injection for ocular delivery. In the present study, antiangiogenic aptamers (anti-vascular endothelial growth factor (VEGF) and anti-angiopoietin-2 (Ang2) aptamers) were conjugated to RNA nanoparticles. The objectives were to investigate the clearance and distribution of these angiogenesis-inhibiting RNA nanoparticles after subconjunctival injection in vivo and their antiangiogenic effects for inhibiting ocular neovascularization in vitro. The results in the whole-body fluorescence imaging study showed that the clearance of RNA nanoparticles was size-dependent with no significant differences between RNA nanoparticles with and without the aptamers except for pRNA-3WJ. The distribution study of RNA nanoparticles by confocal microscopy of the dissected eye tissues in vivo indicated cell internalization of the larger RNA nanoparticles in the retina and retinal pigment epithelium after subconjunctival injection, and the larger nanoparticles with aptamers showed higher levels of cell internalization than those without. In the cell proliferation assay in vitro , RNA nanoparticles with multiple aptamers had higher antiangiogenic effects. With both longer retention time and high antiangiogenic effect, SQR-VEGF-Ang2 could be a promising RNA nanoparticle for posterior eye delivery. [ABSTRACT FROM AUTHOR]

AIM:To verify the safety application of MIL60 in the treatment of corneal neovascularization both in vivo and in vitro. METHODS: We observed the biological characteristics of human corneal epithelial cells. The cell proliferation was analyzed using CCK-8 assay, which also used to test the toxicity of MIL60 and the solvent on cultured human corneal epithelial(HCE). FACs was used to analyze the apoptosis of HCE after treated with MIL60. Also we evaluated the effect of subconjunctival injection of MIL60 on corneal epithelial healing model in normal rat and rats with epithelium defect through slit lamp-microscopy, Draize scores and histopathology way. RESULTS: The proliferation speed of HCE in three groups was the same. MIL60 did no harm on the proliferation of HCE and the apoptosis of HCE, and has no effect on corneal epithelial healing and other parts of the ocular in rats without inflammation cells infiltration. CONCLUSION: When given subconjunctival injection, Mil60 does no harm to the proliferation and apoptosis of HCE, and is safe with ocular application.

Corneal neovascularization (CNV) is one of the major causes of severe disorders in ocular surface. Subconjunctival administration provides a localized and effective delivery of anti-angiogenic agents to inhibit neovascularization. In the present study, the ABA triblock copolymer of poly(D,L-lactic-co-glycolic acid)-block-poly(ethylene glycol)-block-poly(D,L-lactic-co-glycolic acid) (PLGA-PEG-PLGA) was used as a sustained drug delivery carrier for metformin (MET) and levofloxacin hydrochloride (LFH). Both drugs and PLGA-PEG-PLGA copolymers could be easily dissolved in water at low or room temperature and the mixed solution could form a drug-loaded thermosensitive hydrogel in terms of body temperature response. The in vitro release investigation displayed a sustained release of MET and LFH from the formulation for one month. The in vivo efficacy of subconjunctival injection of the MET + LFH loaded thermosensitive hydrogel in inhibiting CNV was evaluated on a mouse model of corneal alkali burn. Compared with the single administration of MET or LFH loaded thermosensitive hydrogel, the MET + LFH loaded thermosensitive hydrogel remarkably inhibited the formation of CNV. The sustained release of MET and an antibiotic (LFH) provides synergistic therapeutic outcome. As a result, the co-delivery of MET and LFH using PLGA-PEG-PLGA thermosensitive hydrogel by subconjunctival injection has great potential for ocular anti-angiogenic therapy. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the safety of subconjunctival injection of doxycycline in rabbit eyes. Methods: Eight white New Zealand rabbits were selected. Different concentrations of 250 micrograms (μg), 500 μg, 1000 μg, and 2000 μg in 0.1 ml were prepared for subconjunctival injection. Each concentration was injected into the two eyes of each rabbit. For each dose, dextrose was injected in one contralateral eye and the other fellow eye remained non-injected. All rabbits underwent ocular examination in the 1st, 3rd, and 30th day after injection. The rabbits were sacrificed 30 days after injections and the histopathological examination was performed. Results: No obvious change was detected in all four groups from the 1st day to the 3rd day after injection in terms of tearing, hyperaemia, and chemosis. There was no visible sign of inflammation or necrosis, and also no histological change in both clinical and histopathological examinations. Conclusion: Subconjunctival injection of doxycycline with different dosages of 250 to 2000 ug in 0.1cc in rabbit eyes was safe and no clinical or histological changes were observed after one month. [ABSTRACT FROM AUTHOR]

Challenges of ophthalmic drug delivery arise from not only the limited solubility of hydrophobic therapeutics, but also the restricted permeability and fast clearance of drugs due to the complex anatomy and physiology of the eyes. Biodegradable thermosensitive polymer, poly(dl-lactide-co-glycolide-b–ethylene glycol-b-dl-lactide-co-glycolide) (PLGA-PEG-PLGA) is a desirable ophthalmic drug delivery system because it can be formulated into injectable solution which forms gel in situ to provide prolonged drug release. In this study, excellent biocompatibility of blank PLGA-PEG-PLGA (1800-1500-1800) thermogel was demonstrated with insignificant difference from saline noted in rat eye enucleation test, in vivo inflammation test upon topical instillation, and subconjunctival injection. After subconjunctival injection, thermogel formulations loaded with hydrophilic (rhodamine B) or hydrophobic (coumarin 6) fluorescent dyes were retained up to 4 weeks in eye tissues and significantly higher level was detected than rhodamine B solution or coumarin 6 suspension in weeks 3 and 4. Moreover, in vivo whole body imaging showed that dye-loaded (sulfo-cyanine 7 NHS ester, Cy7; or cyanine 7.5 alkyne, Cy7.5) thermogels had longer retention at the injection site and retarded release to other body parts than dye solutions. Generally, the release rate of hydrophobic dyes (coumarin 6 and Cy7.5) was much slower than that of the hydrophilic dyes (rhodamine B and Cy7) from the thermogel. In summary, the thermogel was safe for ophthalmic drug delivery and could deliver both hydrophobic and hydrophilic compounds for sustained drug release into eye tissues with single subconjunctival injection for better patient compliance and reduced risks on repeated injection. [ABSTRACT FROM AUTHOR]

Abstract: Importance: The effect of subconjunctival Bevacizumab injection on the outcome of Ahmed glaucoma valve (AGV) implantation. Background: Evaluation of efficacy and safety of subconjunctival Bevacizumab injection adjunctive to AGV implantation. Design: Prospective and randomized clinical trial. Participants: Fifty eyes of 50 patients with diagnosis of glaucoma that were candidate for AGV surgery were included. Methods: In 25 eyes, conventional AGV surgery (group 1) and in 25 eyes AGV surgery with subconjunctival Bevacizumab (group 2) was performed by block randomization Main Outcome Measures: The primary outcome measure was surgical success. Outcome measures were compared at postoperative month 3, 6 and 12. Results: Mean age of patients was 58.76 ± 12.11 and 51.36 ± 15.44 years in group 1 and 2 respectively (P = 0.06). Mean intraocular pressure (IOP) at baseline was 24.88 ± 7.62 mmHg in group 1 and 27.52 ± 8.57 mmHg in group 2 which decreased to15.4 ± 4.4 mmHg in group 1 and 13.42 ± 2.9 mmHg in group 2 (P < 0.00) at last follow up. Surgical success was defined in two level: postoperative IOP ≤ 21 mmHg with at least 20% reduction in IOP (Criterion A), either with no medication (complete success) or with no more than two medications (qualified success) and criterion B with the same definition but the IOP ≤ 18 mmHg The cumulative success according to criterion A and B was 77.8%, 72.2% in group 1 and 89.5% in group 2, respectively, at the end of follow‐up. Conclusions and Relevance: Subconjunctival injection of Bevacizumab adjunctive to AGV implantation leads to higher success rate compared with AGV alone in one year follow‐up. [ABSTRACT FROM AUTHOR]

AIM:To evaluate the clinical effect of subconjunctival injection of triamcinolone acetonide in patients with macular edema secondary to uveitis. METHODS:Sixty-eight patients(82 eyes)with macular edema secondary to uveitis selected in our hospital from October 2014 to October 2015 were assigned into control group and experimental group according to random number table method, with 34 cases(41 eyes)in each group. Patients in the control group were treated by intraocular injection of triamcinolone acetonide, and patients in the experimental group were given subconjunctival injection of triamcinolone acetonide. Clinical effect, central macular thickness and adverse reactions in the two groups were compared. RESULTS:There was no significant difference on the central macular thickness and best corrected visual acuity between the two groups before treatment(P>0.05). Central macular thickness in the experimental group after treatment(214.26±65.54 μm)was significantly lower than that in the control group after treatment(256.47±84.52 μm,PPPPCONCLUSION:Subconjunctival injection of triamcinolone acetonide exerts obvious effect in uveitis patients with macular edema, effectively improves visual acuity, alleviates macular edema and reduces the incidence of intraocular pressure increasing, conjunctival hemorrhage and other adverse reactions, which is safe and effective, thus has potential application.

Nanoparticles fabricated from the biodegradable and biocompatible polymer, polylactic-co-glycolic acid (PLGA), could be a promising system for targeting ocular drug delivery. The objective of this work was to investigate the possibility of encapsulating brinzolamide in PLGA nanoparticles in order to be applied as a subconjunctival injection that could represent a starting point for developing new therapeutic strategies against increase in ocular pressure. The brinzolamide-loaded PLGA nanoparticles were fabricated using emulsion-diffusion-evaporation method with varying concentrations of Tween 80 or poloxamer 188 (Plx) in aqueous and organic phases. The nanoparticles were characterized in terms of particle size and size distribution, entrapment efficiency and in- vitro drug release pattern as well as DSC and X-ray analysis. Nanoparticles prepared using Tween 80 in the aqueous phase showed higher encapsulation efficiency and smaller particle size-values compared to those prepared using Plx. Furthermore, the addition of Plx 188 or Brij 97 to the organic phase in the formulation containing Tween 80 in the aqueous phase led to an increase in the particle diameter-values of the obtained nanoparticles. The nanoparticles had the capacity to release the brinzolamide in a biphasic release profile. The nanoparticles were spherical in shape and the drug was entraped in the nanoparticles in an amorphous form. Selected nanoparticles, injected subconjunctivally in normotensive Albino rabbits, were able to reduce the IOP for up to 10 days. Nanoparticles loaded with brinzolamide with lower particle size were able to reduce the IOP for longer period compared to those with higher particle size. Histopathological studies for the anterior cross sections of the rabbits' eyes revealed that the tested nanoparticles were compatible with the ocular tissue. The overall results support that PLGA nanoparticles, applied as subconjunctival injection, can be considered as a promising carrier for ocular brinzolamide delivery with targeting delivery of the drug to the eye tissues. [ABSTRACT FROM AUTHOR]

Objective Corneal ulcers are commonly encountered in pinnipeds. Prolonged oral antibiotics and topical ophthalmic solutions may not be practical to administer, and novel treatment techniques are desired. Thermodynamic gels are a potential solution because they hold antimicrobials at the site of injection, slowly releasing drug. This study investigated the clinical efficacy of antibiotic-impregnated poloxamer gel in management of corneal ulceration. Animal studied Twenty-six California sea lions undergoing rehabilitation at The Marine Mammal Center. Procedures A poloxamer gel mixed with 2% enrofloxacin was subconjunctivally injected in the treatment group. Control animals received oral doxycycline. Systemic anti-inflammatories and analgesics were administered as needed. Corneal examinations under general anesthesia were repeated weekly, and included sampling for bacterial culture and corneal cytology, collection of high-quality corneal images, and treatment administration until the ulcers were healed. Results There was no gross or histologic evidence of a localized tissue reaction to the gel administration in the conjunctiva, and no evidence of systemic reaction to therapy in animals that died due to unrelated causes during the study period ( n = 17). In animals that experienced a superficial corneal ulcer involving only epithelium or superficial stroma ( n = 12), all lesions resolved completely, in both treatment and control groups. Of those animals with deeper or more complex ulcers involving keratomalacia or descemetoceles ( n = 15), four demonstrated complete lesion resolution (all four received gel treatment). Conclusions This study demonstrates that subconjunctival antibiotic poloxamer gel administration is a safe and effective alternative therapeutic option to traditional treatments for superficial corneal ulceration in pinnipeds. [ABSTRACT FROM AUTHOR]

Objective: To study the efficacy of Conbercept for the treatment of corneal neovascularization (NV) in a rabbit model., Methods: NV was induced by placing sutures. Eight rabbits were used as a control. The other 136 rabbits were randomly divided into two equal groups, and 68 rabbits in each group were divided into four subgroups and given different treatments. Time-course photographs, histological examination, and enzyme-linked immunoassay ELISA analysis for vascular endothelial growth factor were performed at weeks 1, 2, and 3 after injection placement., Results: At weeks 1, 2, and 3 after injection placement, there was less expression of corneal NV and VEGF in the conbercept-treated groups than in the saline-treated control groups and less corneal NV and VEGF were expressed in the early treatment group than in the late treatment group. At weeks 2 and 3 after injection, there were fewer corneal NV (length and area) in the early intrastromal injection group with conbercept than in the early subconjunctival injection group with conbercept and a smaller diameter of corneal NV than in the late intrastromal injection group treated with conbercept. Histological examination showed a smaller diameter of corneal NV in all eyes in conbercept-treated groups 1 w after injection than before injection. Treatment with subconjunctival injection with conbercept led to a larger diameter at weeks 2 and 3 than at week 1., Conclusions: Subconjunctival and intrastromal administrations of conbercept effectively inhibit corneal NV in rabbits, and the latter has the better effect. The effect is the best in the group with cornea intrastromal injection of conbercept 1 w after suture. Early administration of conbercept may successfully inhibit corneal NV in an animal model.

AIM:To compare the efficacies of subconjunctival bevacizumab, ranibizumab, and pegaptanib sodium injections for the inhibition of corneal neovascularization in an experimental rat model.METHODS:Sixteen corneas of 16 rats were chemically cauterized and randomized into four groups:bevacizumab group that treated with 0.05mL/1.25mg bevacizumab, ranibizumab group that treated with 0.05mL/0.5mg ranibizumab, pegaptanib group that treated with 0.05mL/0.15mg pegaptanib sodium, and control group that treated with 0.05mL saline solution. Digital photographs of the corneas were taken and analyzed using an image analysis software program. All corneas were excised and examined histologically on the 15th day.RESULTS: Each treatment group had significantly less neovascularized corneal areas and fewer blood vessels than the control group (all P0.05). CONCLUSION:Subconjunctival bevacizumab, ranibizumab, and pegaptanib sodium were effective with no corneal epitheliopathy for inhibiting corneal neovascularization after corneal burn in rats. Bevacizumab was more effective than ranibizumab and pegaptanib sodium