Comparing Intracanalicular and Topical Steroid Use in Patients Undergoing Pterygium Surgery.

OBJECTIVE: The study received funding from Ocular Therapeutix, Inc., Bedford, MA.We undertook this study to compare the efficacy of intracanalicular dexamethasone 0.4 mg with topical prednisolone acetate (PA) 1% in controlling postoperative pain and inflammation in patients undergoing pterygium surgery. METHODS: This was an open-label, prospective, interventional, nonrandomized comparative trial. Thirty patients were assigned to one of the following groups: Group A [intracanalicular insert of 0.4 mg dexamethasone placed into upper and lower puncta during the procedure, followed by at postoperative month 1 visit institution of topical PA 1% twice daily × 2 weeks then once daily × 2 weeks] or Group B [nonintervention group with institution on postoperative day 1 topical PA 1% every 2 hours × 2 weeks then four times per day × 2 weeks then twice daily × 2 weeks then once daily × 2 weeks]. RESULTS: Fifteen cases and 15 controls were enrolled. There was no statistical difference in patient-reported pain or satisfaction between the case and control groups at 1 day; 1 week; and 1, 3, and 6 months postoperatively. There was no significant difference in time to an ocular hyperemia score of 0 between the two groups. There was no difference in the rate of corneal reepithelialization and recurrence rate (two controls). Nine eyes had transient ocular hypertension (seven cases and two controls). CONCLUSION: Intracanalicular dexamethasone 0.4 mg may reduce the medication burden for patients who need prolonged postoperative steroid therapy as is routine in the setting of pterygium surgery. It is a safe and effective alternative to PA 1% drops alone for postoperative control of pain and inflammation in pterygium surgery.

[Intralesional Injections of 5-Fluorouracil: innovative and effective treatment of Primary Pterygium]. / Inyecciones Intralesionales de 5-Fluorouracilo: tratamiento innovador y efectivo de Pterigión Primario.

OBJECTIVES: To determine the effectiveness of intralesional 5-Fluorouracil (5-FU) in symptomatic relief, astigmatism, and desire for surgery in patients with primary pterygium. METHODS: The experimental study was carried out between January and March 2020 in the Ophthalmology Unit of the Hospital del Salvador, Chile. Fourteen eyes (14 patients) were selected on the surgical waiting list and exposed to fortnightly intralesional injections of 10 mg of 5-FU. An initial evaluation was performed with OSDI for symptomatic measurement, a photographic camera and slit lamp for clinical appearance, and an auto-refractometer for astigmatism, being re-evaluated 60 days later, adding the question of whether they maintained the desire to undergo surgery. The sample was divided into groups A and B depending on whether they received two or one dose of 5-FU, respectively. RESULTS: The average age of the participants was 56.8 ± 11.1 years. Group A presented an initial OSDI of 50 ± 23.8, which, after the intervention, decreased to 21 ± 13.5 (p < 0.001). Group B had an initial OSDI of 47 ± 17.3, decreasing to 22 ± 16.2 (p < 0.005)-statistically significant changes. The degree of astigmatism had no changes. Regarding the physical aspect, there was a reduction in the size of the lesion in 2 of the 14 patients, both in group A. Two patients decided not to undergo surgery after the intervention. CONCLUSIONS: The intralesional injection of 5-FU showed a significant improvement in symptomatic relief without associated complications, generating a therapeutic alternative in patients with primary pterygium without surgical indication.

Resveratrol inhibits TGF-ß1-induced fibrotic effects in human pterygium fibroblasts.

BACKGROUND: Resveratrol is a polyphenolic phytoalexin which has the properties of anti-oxidant, anti-inflammatory and anti-fibrotic effects. The aim of this study was to investigate the anti-fibrotic effects of resveratrol in primary human pterygium fibroblasts (HPFs) and elucidate the underlying mechanisms. METHOD: Profibrotic activation was induced by transforming growth factor-beta1 (TGF-ß1). The expression of profibrotic markers, including type 1 collagen (COL1), α-smooth muscle actin (α-SMA), and fibronectin, were detected by western blot and quantitative real-time-PCR after treatment with various concentrations of resveratrol in HPFs to investigate the anti-fibrotic effects. Relative signaling pathways downstream of TGF-ß1 were detected by Western blot to assess the underlying mechanism. Cell viability and apoptosis were assessed using CCK-8 assay and flow cytometry to evaluate proliferation and drug-induced cytotoxicity. Cell migration and contractile phenotype were detected through wound healing assay and collagen gel contraction assay. RESULTS: The expression of α-SMA, FN and COL1 induced by TGF-ß1 were suppressed by treatment with resveratrol in dose-dependent manner. The Smad3, mitogen-activated protein kinase (p38 MAPK) and phosphatidylinositol-3-kinase (PI3K) / protein kinase B (AKT) pathways were activated by TGF-ß1, while resveratrol attenuated those pathways. Resveratrol also inhibited cellular proliferation, migration and contractile phenotype, and induced apoptosis in HPFs. CONCLUSIONS: Resveratrol inhibit TGF-ß1-induced myofibroblast activation and extra cellular matrix synthesis in HPFs, at least partly, by regulating the TGF-ß/Smad3, p38 MAPK and PI3K/AKT pathways.

Hydroxychloroquine treatment on SARS-CoV-2 receptor ACE2, TMPRSS2 and NRP1 expression in human primary pterygium and conjunctival cells.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen for coronavirus disease 2019 (COVID-19) pandemic. Its infection depends on the binding of spike protein to the host cell receptor angiotensin-converting enzyme 2 (ACE2), type II transmembrane serine protease (TMPRSS2) and neuropilin-1 (NRP1). Hydroxychloroquine has been applied as one of the COVID-19 treatment strategies. Here we aimed to evaluate hydroxychloroquine treatment on SARS-CoV-2 receptor expression in human primary pterygium and conjunctival cells and its potential influences. Expression of ACE2, TMPRSS2 and NRP1 proteins were found in the epithelial layer of both primary pterygium and conjunctiva tissues as well as in their isolated fibroblasts. High concentration of hydroxychloroquine treatment significantly reduced the viability of both primary pterygium and conjunctival cells. ACE2 protein expression was significantly decreased in both pterygium and conjunctival cells after hydroxychloroquine treatment. Hydroxychloroquine also reduced NRP1 protein expression in conjunctival cells. In contrast, TMPRSS2 protein expression showed slightly increased in conjunctival cells. Notably, ROS production and SOD2 expression was significantly elevated in both pterygium and conjunctival cells after hydroxychloroquine treatment. In summary, this study revealed the reduction of ACE2 and NRP1 expression by hydroxychloroquine in human primary pterygium and conjunctival fibroblasts; yet with the increase in TMPRSS2 expression and oxidative stress and decrease in cell viability. Implementation of hydroxychloroquine for COVID-19 treatment should be carefully considered with its potential side effects and in combination with TMPRSS2 inhibitor.

Development and Characterization of Curcumin-Silver Nanoparticles as a Promising Formulation to Test on Human Pterygium-Derived Keratinocytes.

Pterygium is a progressive disease of the human eye arising from sub-conjunctival tissue and extending onto the cornea. Due to its invasive growth, pterygium can reach the pupil compromising visual function. Currently available medical treatments have limited success in suppressing efficiently the disease. Previous studies have demonstrated that curcumin, polyphenol isolated from the rhizome of Curcuma longa, induces apoptosis of human pterygium fibroblasts in a dose- and time-dependent manner showing promising activity in the treatment of this ophthalmic disease. However, this molecule is not very soluble in water in either neutral or acidic pH and is only slightly more soluble in alkaline conditions, while its dissolving in organic solvents drastically reduces its potential use for biomedical applications. A nanoformulation of curcumin stabilized silver nanoparticles (Cur-AgNPs) seems an effective strategy to increase the bioavailability of curcumin without inducing toxic effects. In fact, silver nitrates have been used safely for the treatment of many ophthalmic conditions and diseases for a long time and the concentration of AgNPs in this formulation is quite low. The synthesis of this new compound was achieved through a modified Bettini's method adapted to improve the quality of the product intended for human use. Indeed, the pH of the reaction was changed to 9, the temperature of the reaction was increased from 90 °C to 100 °C and after the synthesis the Cur-AgNPs were dispersed in Borax buffer using a dialysis step to improve the biocompatibility of the formulation. This new compound will be able to deliver both components (curcumin and silver) at the same time to the affected tissue, representing an alternative and a more sophisticated strategy for the treatment of human pterygium. Further in vitro and in vivo assays will be required to validate this formulation.

Corneal Healing and Recovery of Ocular Crystallinity with a Dichloromethane Extract of Sedum dendroideum D.C. in a Novel Murine Model of Ocular Pterygium.

Pterygium is a corneal alteration that can cause visual impairment, which has been traditionally treated with the sap of Sedum dendroideum D.C. The pharmacological effect of a dichloromethane extract of S. dendroideum was demonstrated and implemented in a pterygium model on the healing process of corneal damage caused by phorbol esters. In mice of the ICR strain, a corneal lesion was caused by intravitreal injection of tetradecanoylphorbol acetate (TPA). The evolution of the corneal scarring process was monitored with vehicle, dexamethasone, and dichloromethane extract of S. dendroideum treatments by daily ophthalmic administration for fifteen days. The lesions were evaluated in situ with highlighted images of fluorescence of the lesions. Following treatment levels in eyeballs of IL-1α, TNF-α, and IL-10 cytokines were measured. The effective dose of TPA to produce a pterygium-like lesion was determined. The follow-up of the evolution of the scarring process allowed us to define that the treatment with S. dendroideum improved the experimental pterygium and had an immunomodulatory effect by decreasing TNF-α, IL-1α, and maintaining the level of IL-10 expression, without difference with respect to the healthy control. Traditional medical use of S. dendroideum sap to treat pterygium is fully justified by its compound composition.

Anti-fibrosis potential of pirarubicin via inducing apoptotic and autophagic cell death in rabbit conjunctiva.

This study investigated the potential efficacy of pirarubicin (THP) in modulating rabbit conjunctival fibrosis both in vitro and in vivo and characterized the underlying mechanisms. Primary rabbit conjunctival fibroblasts (RCF) were cultured and treated with THP or mitomycin C (MMC) for 5 min, followed by assaying for cell viability, cell cycle distribution, apoptotic and autophagic pathways. The production of reactive oxygen species (ROS) and chemotaxis of macrophages by RCF were evaluated using 2',7'-dichlorofluorescein diacetate (DCFH-DA) labeling and transwell migration assay, respectively. Limbal stem cell excision in combination with alkali burn was performed on the rabbits to establish a model of limbal deficiency and conjunctival fibro-vascular invasion. After three months, the modeled fibro-vascular tissue was excised combined with topical subconjunctival 5-min exposure to THP compared with MMC intraoperatively. The recurrence of postoperative fibrosis and the expression of apoptosis, autophagy, and inflammation markers were evaluated by immunohistochemistry. All modeled rabbits developed conjunctival fibro-vascular lesions, which were similar to human recurrent pterygium (HRP). Both THP and MMC inhibited RCF proliferation and arrested cell cycle at the G0/G1 phase. In particular, 7.5 µmol/L THP remarkably promoted RCF autophagy by upregulating the levels of Beclin 1, Atg 5/12 conjugate, and LC3B, whereas, 15 µmol/L THP significantly triggered a cascade of mitochondrial-associated RCF apoptosis. THP induced the production of ROS and enhanced the chemoattraction of macrophages by RCF. Similar to 600 µmol/L MMC, both 7.5 µmol/L and 15 µmol/L THP attenuated postoperative conjunctival fibrosis in the models; 7.5 µmol/L THP preferentially enhanced autophagy while causing fewer side effects. THP exerted its antifibrotic action by modulating autophagy in RCF, inducing cell cycle arrest, and mitochondrial-mediated apoptosis. THP at the dose of 7.5 µmol/L prevented postoperative conjunctival fibrosis in an animal model.

Targeted delivery of mitomycin C-loaded and LDL-conjugated mesoporous silica nanoparticles for inhibiting the proliferation of pterygium subconjunctival fibroblasts.

Pterygium is a degenerative disease that characterized by excessive fibrovascular proliferation. To reduce the recurrence rate, surgery is the main strategy, in combination with adjacent procedures or adjunctive therapy. One of the most common adjunctive agents, mitomycin C (MMC), is known as an alkylating agent that inhibits fibroblast proliferation but is limitedly applied in pterygium due to various complications. A previous study demonstrated that activated pterygium subconjunctival fibroblasts overexpressed low-density lipoprotein (LDL) receptors. In this study, we designed and synthesized MMC-loaded mesoporous silica nanoparticles conjugated with LDL (MMC@MSNs-LDL) to deliver MMC into activated pterygium fibroblasts in a targeted manner. The MMC loading efficiency was approximately 6%. The cell viability test (CCK-8 assay) revealed no cytotoxicity for the empty carrier MSNs at a concentration of ≤1 mg/ml after administration for 48 h in subconjunctival fibroblasts. Primary pterygium and normal human subconjunctival fibroblasts with or without stimulation by vascular endothelial growth factor (VEGF) were treated as follows: 1) 10 µg/ml MMC@MSNs-LDL for 24 h (MMC concentration: 0.6 µg/ml); 2) 0.2 mg/ml MMC for 5 min then cultured for 24 h after MMC removal; and 3) normal culture without any drug treatment. At 24 h, the anti-proliferative effect of MMC@MSNs-LDL in activated pterygium fibroblasts was similar to that of MMC (cell viability: 46.2 ± 5.5% vs 40.5 ± 1.1%, respectively, P = 0.349). Furthermore, the cytotoxicity of MMC@MSNs-LDL to normal fibroblasts with or without VEGF stimulation was significantly lower than that of traditional MMC (cell viability: 75.6 ± 4.4% vs 36.0 ± 1.5%, respectively, P < 0.001; 84.7 ± 5.5% vs 35.7 ± 1.3%, P < 0.001). The binding of fluorescently labeled MMC@MSNs-LDL in fibroblasts was assessed using confocal fluorescence microscopy. The uptake of targeted nanoparticles in fibroblasts was time dependent and saturated at 6 h. VEGF-activated pterygium fibroblasts showed more uptake of MMC@MSNs-LDL than normal fibroblasts with or without VEGF activation (both P < 0.001). Our data strongly suggest that MMC@MSNs-LDL had an effective antiproliferative role in activated pterygium fibroblasts, with reduced toxicity to normal fibroblasts compared to traditional application of MMC. LDL-mediated drug delivery might have great potential in the management of pterygium recurrence.

The in vitro anti-fibrotic effect of Pirfenidone on human pterygium fibroblasts is associated with down-regulation of autocrine TGF-ß and MMP-1.

We aimed to investigate the in vitro effect of pirfenidone (PFD) on proliferation, migration and collagen contraction of human pterygium fibroblasts (HPFs). HPFs were obtained from tissue explants during pterygium surgery. After treatment with pirfenidone, the HPFs proliferation was measured by MTT, cell cycle progression measured by flow cytometry, cell migration measured by the scratch assay, and cell contractility evaluated in fibroblast-populated collagen gels. The expression of TGF-ß1, TGF-ß2, MMP-1 and TIMP-1 were also determined with quantitative PCR, western blot and immunofluorescence staining. Results showed pirfenidone markedly inhibited HPFs proliferation with an IC50 of approximately 0.2 mg/ml. After treatment with 0.2 mg/ml pirfenidone for 24 hours, HPFs were at G0/G1 cell cycle arrest, with significantly reduced cell migration capability and collagen contraction, decreased mRNA and protein expressions of TGF-ß1, TGF-ß2 and MMP-1, and no alterations of TIMP-1 expression. Thus, we have concluded that pirfenidone at 0.2 mg/ml inhibits proliferation, migration, and collagen contraction of HPFs, which is associated with decreased expression of TGF-ß and MMP-1, and pirfenidone might represent a potentially therapeutic agent to prevent the recurrence of pterygium after surgery.

Efficacy of bevacizumab injection after pterygium excision and limbal conjunctival autograft with limbal fixation suture.

PURPOSE: To determine the efficacy of subconjunctival bevacizumab injection after pterygium excision with limbal conjunctival autograft and limbal fixation suture. METHODS: This retrospective study included a total of 150 eyes of 150 patients with primary pterygium who received three different procedures after pterygium excision, i.e., 49 eyes with limbal conjunctival graft (group A), 48 eyes with limbal conjunctival autograft with limbal fixation suture (group B), and 53 eyes with limbal conjunctival autograft with limbal fixation suture followed by bevacizumab injection (group C). Image analysis was performed using preoperative anterior segment photographs to measure parameters including relative length, relative width, relative area, and vascularity index of pterygium. Recurrence of pterygium was determined at 1 year after surgery, and outcomes were compared between the 3 groups. Risk factors related to recurrence were evaluated using univariate and multivariate analyses. RESULTS: Recurrence rates after 1 year were 18.4% (9/49), 8.3% (4/48), and 1.9% (1/53) in groups A, B, and C, respectively (P = 0.004). Multivariate analysis showed that patients in group C had significantly reduced risk of recurrence compared with those in group A (P = 0.009), whereas the risk of recurrence was not significantly different between groups A and B (P = 0.227) and groups B and C (P = 0.068), respectively. Among various parameters, higher vascularity index had significant correlation with increased risk of recurrence (P = 0.008). CONCLUSIONS: Bevacizumab injection after limbal conjunctival autograft and limbal fixation suture may effectively reduce recurrence after pterygium excision. The vascularity of pterygium was associated with a higher risk of recurrence.

[Preliminary observation on the treatment of primary pterygium with modified conjunctival transplantation and amniotic membrane transplantation combined with use of interferon eye drops].

Objective: To observe the clinical effect of modified conjunctival transplantation and amniotic membrane transplantation combined with use of interferon (IFN) alpha-2b eye drops in the treatment of primary pterygium. Methods: This was a prospective case-control study. Patients with primary pterygium were treated from June 1, 2018 to December 31, 2018 in the Department of Ophthalmology, Beijing Tongren Hospital, and they were divided into two groups (the experimental group and the control group) by the method of randomized block design. Patients in the experimental group received modified conjunctival transplantation and amniotic membrane transplantation combined with use of IFN alpha-2b eye drops, while patients in the control group received pterygium resection combined with conjunctival autograft transplantation. The pterygium type and size were observed before operation, while visual acuity, intraocular pressure and anterior segment details were recorded either. The follow-up was done at 1 week, 2 weeks, 1 month, 3 months, 6 months and 12 months after operation. The visual acuity, corneal epithelial defect, and pterygium recurrence were observed. All data in this manuscript are enumeration data, the expected frequency of pterygium type distribution in the two groups was more than 5, and the chi square test was used, fisher's exact test was used to compare the other data between the two groups. Results: Seventy patients (77 eyes) with pterygium were in this study, including 30 males and 40 females, aged from 50-70 years old. There were 35 cases (38 eyes) in the experimental group and 35 cases (39 eyes) in the control group. 12 months after operation there were 54 cases (60 eyes) including 28 cases (30 eyes) in the experimental group and 26 cases (30 eyes) in the control group with complete data. The corneal epithelium defects of 1 eye in each group was repaired within 7-14 days after operation, and the rest eyes were completely repaired within 7 days after operation. There was no significant difference in the distribution of corneal epithelial healing between the two groups (P= 1.00). There was no significant difference between the two groups in the number of eyes distribute with decreased visual acuity (2 eyes in each group), stable visual acuity (15 eyes in the experimental group and 23 eyes in the control group), and improved visual acuity (13 eyes in the experimental group and 5 eyes in the control group) (P=0.053). There was no recurrence in the two groups at 12 months after surgery, and there was no significant difference between the two groups in the number of patients with conjunctival hyperplasia of grades 1, 2 and 3 (P=0.405). Conclusions: Modified conjunctival transplantation and amniotic membrane transplantation combined with use of IFN alpha-2b eye drops got low recurrence rate for primary pterygium and less damage to the healthy conjunctival tissue. This combined treatment strategy provides a new choice for the treatment of pterygium. (Chin J Ophthalmol, 2020, 56: 768-773).

[Antiangiogenic therapy in the surgical treatment of pterygium]. / Antiangiogennaya terapiya v khirurgicheskom lechenii pterigiuma.

PURPOSE: To evaluate the effectiveness and safety of adjuvant anti-VEGF therapy in the surgical treatment of pterygium, and to determine the indications for its use. MATERIAL AND METHODS: The study included 67 patients (69 eyes) with grade II-IV pterygium. Patients age was 58.8±12.6 years on average. Best corrected visual acuity (BCVA) varied between 0.01 and 1.0 (0.77±0.24). The patients were divided into 3 groups. The first group included 19 patients (19 eyes) with grade II-III pterygium who underwent «bare sclera¼ surgery and used aflibercept as adjuvant therapy. The second group included 21 patients (21 eyes) with grade II-IV pterygium who underwent auto conjunctival grafting surgery with no adjuvant therapy. The third group included 27 patients (29 eyes) with grade II-IV pterygium who had it removed in combination with single-time peripheral lamellar keratoplasty (PLK) and underwent adjuvant aflibercept therapy. RESULTS: Among patients who underwent pterygium excision with adjuvant antiangiogenic therapy there were 5 cases (26%) of relapse during the observation period (23.38±8.96 months), among patients after pterygium excision with auto conjunctival plastic surgery - also 5 cases (24%) of relapse, and among patients who underwent LKP combined with anti-VEGF therapy there was only 1 case (3%) of relapse. Astigmatism has decreased by 0.24±0.5 (p=0.052) in the first group, by 1.21±1.0 (p<0.05) in the second group, and by 1.64±1.54 (p<0.05) in the third group compared with pre-surgical values, thus increasing average BCVA in all 3 patient groups by 0.1±0.13, 0.07±0.11 and 0.15±0.15, respectively. CONCLUSION: The use of anti-VEGF agents as adjuvant therapy in the surgical treatment of pterygium is a safe method of reducing postoperative inflammation, fibrovascular proliferation and, subsequently, the amount of relapses.

Evaluation of antimitotic and antiangiogenic effect of preoperative subconjunctival application of mitomycin C in primary pterygium: a randomized trial.

PURPOSE: To evaluate the influence of preoperative mitomycin C (MMC) on the proliferative behavior of fibroblasts and fibrovascular tissue derived from the primary pterygium using the immunohistochemical method (Ki67 and CD34). DESIGN: Randomized clinical trial. SUBJECTS, PARTICIPANTS AND/OR CONTROLS: Sixty-five patients with primary pterygium were randomly selected and divided into one of three groups. The control group had 29 patients that were only submitted to pterygium removal. The group that received the MMC injection a month before surgery had 16 patients, and the group that received the MMC 2 weeks before surgery had 20 patients. Each patient only had one eye operated on. METHODS: Sixty-five patients were selected to undergo pterygium excision surgery. We randomly placed the patients into three groups: one without MMC (n = 29), one with MMC application 1 month before surgery (n = 16) and another with MMC application 2 weeks before surgery (n = 20). Subconjunctival injection was applied with 0.1 ml of 0.02% MMC in the pterygium body, and patients were followed for 2 years. MAIN OUTCOME MEASURES: Proliferative behavior of fibroblasts and fibrovascular tissue using the immunohistochemical method (Ki67 and CD34) comparing the three groups. RESULTS: Of the total 29 patients (44.6%) in the control group (without MMC application), 11 cases had recurrence (37.9%), of which seven (63.6%) were within 3 months of follow-up and four (36.3%) within 6 months of follow-up. The mean proliferation index of the recurrent cases was 4.5%, and of the cases without recurrence, it was 6.1%. There were 16 patients (24.6%) in the MMC application group 1 month before surgery, in which one case (6.25%) recurred at 6 months. In the group with MMC application 2 weeks before surgery, of the total of 20 patients (30.7%), there was one case of recurrence (5%) at 6 months. The proliferation index of the group that had MMC administered and did not have a recurrence was 7.2%, and in the group with recurrence, it was 6.4%. The CD34-labeled cell count was 5.8% among cases with recurrence and 5.6% in cases without recurrence. No side effects of MMC application were reported during the study follow-up period. CONCLUSION: MMC was efficient to reduce the recurrence index despite the absence of a direct relation with its antimitotic and antiangiogenic effect in the samples that were analyzed.

Conjunctival Autograft Combined With Either Preoperative Mitomycin C Injection or Intraoperative Local Mitomycin C Over the Medial Rectus Muscle Tendon in Primary Pterygium Surgery.

PURPOSE: To evaluate and compare the recurrence rate and complications of conjunctival autograft (CAG) combined with preoperative mitomycin C (MMC) injection versus CAG with intraoperative local MMC over the medial rectus muscle tendon in primary pterygium. STUDY DESIGN: Randomized prospective study. METHODS: This study included 108 eyes of 108 patients with primary fleshy or growing pterygium. All patients were from rural areas and less than 50 years old. Fifty-three patients were treated with injection of 0.1 mL of 0.15 mg/mL MMC into the body of pterygium followed 1 day later by pterygium excision and CAG (group I), and 55 patients were treated with pterygium excision and local application of 0.2 mg/mL MMC for 2 min over the medial rectus tendon followed by CAG (group II). The minimum follow-up period was 18 months. RESULTS: Two patients from group I and one patient from group II did not complete the follow-up period and were excluded. There were no statistically significant differences between the two groups regarding age, sex, laterality, or follow-up period. Recurrence occurred in 2 eyes in group I (3.92%) and 1 eye in group II (1.85%); (P=0.52). All recurrences occurred in male patients of less than 30 years of age. No significant complications were encountered in both groups. CONCLUSIONS: Both preoperative MMC injection followed 1 day later by pterygium excision with CAG, and pterygium excision and intraoperative local application of MMC on the medial rectus tendon are successful in treating primary pterygium with low recurrence rate and few complications.

Cyclosporine A inhibits TGF-ß2-induced myofibroblasts of primary cultured human pterygium fibroblasts.

Cyclosporine A (CsA), an immunomodulatory drug, and is increasingly used to treat moderate dry eye syndrome and ocular surface inflammation. However, any inhibitory effect on differentiation of fibroblasts to myofibroblasts remains unclear. Here, we show that the inhibitory effect of CsA on transforming growth factor-beta2 (TGF-ß2)-induced myofibroblasts in primary cultured human pterygium fibroblasts. CsA significantly decreased mRNA and protein expression of myofibroblast-related markers including α-SMA, laminin, and fibronectin. These findings were supported by the results from immunofluorescence staining. Taken together, these results indicate the therapeutic potential of CsA against pterygium progression. Further studies are necessary to elucidate the precise intracellular signal mechanism responsible for CsA-induced downregulation of myofibroblast markers in pterygium fibroblasts.

Inhibitory effects of rosmarinic acid on pterygium epithelial cells through redox imbalance and induction of extrinsic and intrinsic apoptosis.

Pterygium is a common tumor-like ocular disease, which may be related to exposure to chronic ultraviolet (UV) radiation. Although the standard treatment for pterygium is surgical intervention, the recurrence rate of pterygium is high when no effective inhibitory drug is used after surgery. Rosmarinic acid (RA) is a polyphenol antioxidant with many biological activities, including anti-UV and anti-tumor properties. This study aimed to examine the inhibitory effects of RA on pterygium epithelial cells (PECs). Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay was used to examine the cell cytotoxicity of PECs after RA treatment. A fluorescent probe, DCFH-DA (2',7'-dichlorofluorescin diacetate), was stained with PECs to measure intracellular reactive oxygen species (ROS) levels. Antioxidant activity assays were used to measure the levels of superoxide dismutase (SOD) and catalase (CAT) in PECs. Western blot analysis was used to determine the protein expression of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), quinone acceptor oxidoreductase 1 (NQO1), and apoptosis-associated proteins. RA significantly reduced the cell viability of the PECs. Treatment with RA remarkably increased the Nrf2 protein expression levels in the nucleus, HO-1 and NQO1 protein expression levels, and the activities of SOD and CAT. As a result, intracellular ROS levels in PECs were decreased. Additionally, the induction of extrinsic apoptosis on PECs by RA was associated with increasing expressions levels of Fas, Fas-associated protein with death domain (FADD), tumor necrosis factor-alpha (TNF-α), and caspase 8 protein. Moreover, the induction of intrinsic apoptotic cell death in PECs was confirmed through upregulation of cytochrome c, Bax, caspase 9, and caspase 3 and downregulation of Bcl-2 and pro-caspase 3. Our study demonstrated that RA could inhibit the viability of PECs through regulation of extrinsic and intrinsic apoptosis pathways. Therefore, RA may have potential as a therapeutic medication for pterygium.

Anti-fibrotic, anti-VEGF or radiotherapy treatments as adjuvants for pterygium excision: a systematic review and network meta-analysis.

BACKGROUND: Anti-fibrotic, anti-VEGF (vascular endothelial growth factor) medications, or radiotherapy, as adjuvant for pterygium surgical procedure, has been suggested for reducing recurrence, but difficulties may be experienced in deciding which treatment to use. The purpose of this study was to compare the efficacies of these different adjuvants for preventing recurrence following pterygium surgery. METHODS: We conducted a systematic review to identify randomized controlled trials of patients with primary or recurrent pterygium who received anti-fibrotic, anti-VEGF medication, or radiotherapy as adjuvants in combination with surgical procedure. The surgical procedure contained bare sclera technique or petrygium excision combination with tissue grafting. The primary outcome of this study was recurrence. Direct-comparison and Bayesian network meta-analyses were performed to assess direct and indirect evidence of efficacy. RESULTS: We obtained data from 34 randomized controlled trials, representing a total of 2483 patients. Adjuvants included bevacizumab, 5-FU (5-fluorouracil), MMC (mitomycin C), and ß-RT (beta-radiotherapy). Compared with placebo, we found distinguishable improvement in recurrence with bevacizumab (odds ratio [OR] 0.38, 95% confidence interval [CI] 0.18-0.80), MMC (0.12, 95% CI 0.06-0.21), and ß-RT (0.17, 95% CI 0.04-0.69), but not with 5-FU (0.41, 95% CI 0.12-1.39). MMC significantly reduced recurrence when compared to bevacizumab (0.31, 95% CI 0.13-0.77) and 5-FU (0.28, 95% CI 0.08-0.99). The probability of having the most recurrences after excision was lowest for MMC, followed by bevacizumab and ß-RT. Similar results were found in subgroup analyses, including for primary pterygium, and the patients receiving bare sclera technique or conjunctival autograft. CONCLUSIONS: Adjuvants such as MMC, bevacizumab, and ß-RT could effectively prevent recurrence following pterygium excision. However, their efficacy and acceptability require further clarification in future randomized controlled trials.

Subtenon Injections of Ranibizumab Arrest Growth in Early Recurrent Pterygium.

IMPORTANCE: Currently the only treatment for recurrent pterygium is surgery. This is a phase 1 trial investigating ranibizumab as a medical treatment for recurrent pterygium. OBJECTIVE: To assess the safety and efficacy of subtenon Ranibizimab for recurrent pterygia. DESIGN: Subjects with recurrent pterygium received subtenon ranibizumab and were followed for 1 year. Safety parameters were measured. Photographs were taken and quantitatively analyzed to measure the short-term (2 months) and long-term (5-26 months) response to treatment. SETTING: University of New Mexico Eye Clinic. PARTICIPANTS: Eight subjects with recurrent pterygia. INTERVENTIONS: Subtenon delivery of 0.5 to 2 mg of ranibizumab, at day 0, month 1, and month 2. MAIN OUTCOME MEASURES: Safety parameters included visual acuity, intraocular pressure, and assessment of ocular surface. Efficacy was assessed by comparing photographs taken at day 0 with a short-term follow-up photograph taken at month 2 and a long-term follow-up image taken at the final patient visit (range 5-26 months). Quantitative analysis of photographs was performed to measure vascularity in the treated zone. RESULTS: Four subjects had an arrest of pterygium growth with a visual reduction in vascularity and a quantitative reduction in the area of vascularization (average vascularized area in short-term follow-up images was 51% of the baseline photos at day 0, and in the long-term photos was 36% of day 0). The other four subjects had a less marked reduction in their vascularity in the short-term photos (69% of their baseline photos). This resulted in two subjects withdrawing from the study early. Long-term quantitative analysis for the two remaining "nonresponders," who completed the study, showed an average vascularized area that was 71% of that in their baseline photos. The long-term photos in these subjects did not appear to have a clinically relevant difference from the short-term photos. CONCLUSIONS: In half of the subjects, subtenon ranibizumab appeared to arrest growth. Although the response is variable, this may warrant the drug's use when attempting to control growth of recurrent pterygia, and may prevent consecutive surgery for some patients.

The effect of gatifloxacin 0.3% or moxifloxacin 0.5% on corneal healing, ocular tolerability and toxicity following pterygium surgery.

PURPOSE: To compare the rate of corneal epithelial healing and ocular tolerability following pterygium surgery between gatifloxacin and moxifloxacin. METHODS: In this double masked, prospective, controlled study 40 patients were randomized to receive prophylactic topical gatifloxacin 0.3% or moxifloxacin 0.5% following pterygium surgery. Patients were examined on days 1, 3, 7 and 21 post-operatively or until complete corneal epithelial healing. The primary outcome measure was the area of corneal epithelial defect during the post-operative period. Patients graded post-operative ocular pain, foreign body sensation, tearing, general burning sensation and burning sensation post-antibiotic drops instillation on a scale of 1-5. Conjunctival hyperemia and superficial punctate keratopathy (SPK) were measured on a scale of 0-3. RESULTS: No significant differences between groups were found in terms of corneal epithelial defect percentage over time (p = 0.989) and there was no significant difference between groups on each of the post-operative days. No significant differences were noted in terms of post-operative ocular pain, foreign body sensation, tearing, general burning sensation, burning sensation post-antibiotic drops instillation, conjunctival hyperemia and SPK. CONCLUSIONS: Gatifloxacin and moxifloxacin showed equivalent results in terms of corneal epithelial healing and ocular tolerability following pterygium surgery. This study suggests that there was no apparent added epithelial toxicity due to the presence of benzalkonium chloride in the gatifloxacin preparation when compared to moxifloxacin.

Comparison of primary versus recurrent pterygium after intralesional 5-Fluorouracil.

OBJECTIVE: To compare the mean change in corneal astigmatism and clinical appearance after intralesional injection of 5-Fluorouracil in primary and recurrent pterygia. METHODS: The quasi-experimental study was conducted at the Armed Forces Institute of Ophthalmology, Rawalpindi, Pakistan, from June 2014 to April 2015. The patients were categorised into two groups. Group1 named GP comprised primary pterygia patients, while those of recurrent pterygia were in Group 2 named GR. All the patients were treated with 0.1ml intralesional 5-Fluorouracil 5mg weekly injections for 04 weeks. Ophthalmic clinical evaluation included uncorrected distant visual acuity, keratometery and slit lamp examination was performed before and 04 weeks after the treatment. RESULTS: There were 86 eyes of 64 patients in the study. Mean uncorrected distant visual acuity of patients was 0.12±0.13 in GP and 0.26±0.17 in GR. Mean astigmatism before treatment was 1.75±1.08 in GP and 2.92±2.28 in GR. Same parameters 04 weeks after last injection were 1.66±1.17 and 2.64±1.78 in GP and GR respectively. All eyes had a statistically significant change in clinical appearance. CONCLUSIONS: Intralesional 5-Fluorouracil injection improved cosmesis of primary as well as recurrent pterygia, but did not have statistically significant effect on corneal astigmatism.