Efficacy of bevacizumab in the treatment of pterygium: An updated meta-analysis of randomized controlled trials.

Recurrence is the most common problem following pterygium surgery. Whether bevacizumab can prevent pterygium recurrence is controversial. To address this point, we carried out a meta-analysis of randomized controlled trials evaluating the efficacy and safety of bevacizumab in the treatment of pterygium. We searched the PubMed, EMBASE, Cochrane Library, Web of Science, Chinese Biomedical Literature, China National Knowledge Infrastructure, and Wan fang databases up to September 20, 2020 for relevant articles. We used the Cochrane assessment tool to evaluate the methodologic quality of the included studies, and calculated the relative risk (RR) and 95% confidence interval (CI) of the reported recurrence and complication rates. A total of 17 studies including 1124 patients with 1144 eyes were included in the meta-analysis. The combined results showed that bevacizumab significantly reduced the recurrence rate of pterygium after surgery (RR = 0.652, 95% CI: 0.504-0.845, Z = 3.24, P = 0.001) and was not significantly associated with the occurrence of postoperative complications compared to control treatments (RR = 0.832, 95% CI: 0.604-1.145, Z = 1.13, P = 0.259). A subgroup analysis showed that the rate of pterygium recurrence was significantly lower with bevacizumab than in the control group at a dose of 2.5 mg (RR = 0.47, 95% CI: 0.24-0.91) administered by subconjunctival injection (RR = 0.54, 95% CI: 0.39-0.75) after a follow-up time of ≤ 6 months (RR = 0.63, 95% CI: 0.45-0.88). Thus, bevacizumab can reduce the risk of pterygium recurrence after surgery, and does not differ from placebo or other drug treatments in terms of the risk of complications.

Activation of LncRNA FOXD2-AS1 by H3K27 acetylation regulates VEGF-A expression by sponging miR-205-5p in recurrent pterygium.

LncRNA FOXD2-AS1 is abnormally expressed in many diseases. However, the molecular mechanisms whereby FOXD2-AS1 is involved in recurrent pterygium remain unknown. Here, qRT-PCR was performed to quantify FOXD2-AS1 expression, while CCK-8, flow cytometer and neoplasm xenograft assays were used to investigate its function. Dual-luciferase reporter, RIP and RNA pull-down assays were conducted to address the relationship between FOXD2-AS1, miR-205-5p and VEGF-A, while ChIP assays were used to detect H3K27 acetylation at the FOXD2-AS1 promoter. FOXD2-AS1 expression was up-regulated in recurrent pterygium tissues. Moreover, a high FOXD2-AS1 expression was associated with advanced stages, increased microvessel density and shorter recurrent-free survival. In addition, ROC analysis showed that FOXD2-AS1 is a valid predictor of recurrent pterygium. Furthermore, we show that FOXD2-AS1 induced proliferation and inhibited apoptosis in a cell line derived from recurrent pterygia (HPF-R) at least partially through the regulation of the miR-205-VEGF pathway. In addition, the up-regulation of FOXD2-AS1 was attributed to the H3K27 acetylation at the promoter region. In conclusion, FOXD2-AS1 is activated via its H3K27 acetylation and regulates VEGF-A expression by sponging miR-205-5p in recurrent pterygium. Our results may provide a basis for the development of new therapeutic targets and biomarkers for recurrent pterygium.

Clinical profile of pterygium in patients seeking eye care in India: electronic medical records-driven big data analytics report III.

OBJECTIVE: To describe the clinical profile of pterygium in patients presenting to a multi-tier ophthalmology hospital network in India. METHODS: This cross-sectional hospital-based study included 1,610,843 new patients presenting between 2010 and 2019. Patients with a clinical diagnosis of pterygium in at least one eye were included as cases. The data were collected using an electronic medical record system. Multiple logistic regression analysis with odds ratios (OR) was performed to identify the associated risk factors. RESULTS: Overall, 168,807 (10.5%) new patients were diagnosed with pterygium, of which 43,692 (26%) patients complained about the lesion. The prevalence rates were 0.7% in children and 12.6% in adults. Majority of patients were female (54.5%) and had unilateral (57%) affliction. Among the 241,631 affected eyes, the pterygia were primary in 99.6%, nasally located in 94%, and were grade I-II in 84.8%. Four in 5 eyes did not have any cylindrical refractive error, and 44% had coexistent cataract. Pterygium surgery was indicated in 10.3% eyes. Female sex (OR 1.37), increasing age (OR 19.5), rural residence (OR 1.21), agriculture work (OR 2.19), manual labor (OR 2.05), low socioeconomic status (OR 2.14) and geographical location closer to the equator (OR 3.4) were identified as the risk factors for developing pterygium. CONCLUSION: About one-tenth of individuals seeking eye care in India have pterygium in at least one eye. It rarely impacts vision, is commonly unilateral and nasal and usually does not require surgery. It is associated with increasing age, females, outdoor work, low income and geographical location closer to the equator.

Fifteen-year results of a randomized controlled trial comparing 0.02% mitomycin C, limbal conjunctival autograft, and combined mitomycin C with limbal conjunctival autograft in recurrent pterygium surgery.

PURPOSE: To compare the long-term outcomes of recurrent pterygium surgery between three different techniques. METHODS: We performed a 15-year follow-up study of a randomized controlled study on surgical management of recurrent pterygium. Group 1 received limbal conjunctival autograft (LCAU); group 2 received intraoperative mitomycin C (MMC) 0.02% for 5 min; and group 3 received combined LCAU + MMC 0.02% for 5 min. Consecutive patients enrolled in the original study (from April 2001 to March 2003) were invited back for a detailed clinical examination to document the long-term outcomes. The main outcome measures included the recurrence rate, residual conjunctival bed status, and complications from any of the surgical methods. RESULTS: Sixty-two patients were recruited in the original study. Eight patients had passed away and 12 patients were uncontactable or not responded. One patient who had bilateral operations refused to return for follow-up and one eye had insufficient data for analysis. Finally, 40 eyes of 40 patients were included for analyses. One eye developed a recurrence over 15 years and none required a tertiary pterygium operation. The patient received LCAU for a temporal recurrent pterygium developed a 2.2-mm recurrence. CONCLUSIONS: All three techniques yielded favorable outcomes for patients with recurrent pterygium. The use of LCAU was associated with better cosmetic outcome.

Interferon Alpha-2b Eye Drops Prevent Recurrence of Pterygium After the Bare Sclera Technique: A Single-Center, Sequential, and Controlled Study.

PURPOSE: To investigate the efficacy and safety of interferon (IFN) alpha-2b eye drops in preventing pterygium recurrence after the bare sclera technique. METHODS: Sixty eyes in 53 patients who underwent treatment for primary pterygium (the length of corneal invasion ranged from 2 to 4 mm) were enrolled in this prospective study. All patients were divided in chronological sequence into 2 groups. The control group included the first 30 eyes, whereas the treatment group included the next 30 eyes. After treatment with the bare sclera technique, levofloxacin and 0.1% fluorometholone eye drops were used 4 times a day for 3 months after surgical excision in both groups. In addition, IFN alpha-2b eye drops were applied in the treatment group 4 times a day for 3 months. Throughout an 18-month follow-up period, all patients in both groups were examined 1 day, 10 days, 1 month, 3 months, 6 months, 12 months, and 18 months after surgery. The main outcome measures were pterygium recurrence, conjunctival redness and thickness, and neovascularization and complications (ie, delayed conjunctival healing, persistent corneal epithelial defection, conjunctival granuloma, and scleral melting and necrosis). RESULTS: The recurrence rates in the control group and the treatment group at the end of the sixth month were 29.2% and 3.7%, respectively, and the rates were significantly different between the 2 groups (P = 0.019). Up to 12 months after surgeries, the recurrence rate was 33.3% in the control group and 7.4% in the treatment group, and the difference between the 2 groups was statistically significant (P = 0.048). The rates at the end of 18 months were the same. During the follow-up period, no complications were observed except for 1 conjunctival granuloma (in the treatment group) and 2 corneal epithelial defects (one in the control group and the other in the treatment group). CONCLUSIONS: Administration of IFN alpha-2b eye drops after the bare sclera technique appear safe and effective in reducing the recurrence of pterygium.

Signaling roadmap to epithelial-mesenchymal transition in pterygium, TWIST1 centralized.

Pterygium as a complex disease shares common features with other malignant cells in its onset recurrence and especially epithelial-mesenchymal transition (EMT) transition. Although using different approaches including conjunctival autografts, amniotic membrane, radiotherapy, mitomycin C (MMC) has shown promising insights in the inhibition of pterygium recurrence, it needs to be investigated in more details in molecular pathways to present adjuvant target therapy. In this study, we aimed to evaluate the expression of and then illustrate the role of signaling pathways on EMT in pterygium. Using real-time polymerase chain reaction, the twist-related protein 1 (TWIST1) expression was compared in primary pterygium and normal conjunctiva. This study assessed the mRNA expression, as well as the association between the clinicopathological indices and the gene expression level. The expression level of TWIST1 was overexpressed in 36% of our cohort ( n = 76). There was a significant positive correlation between recurrence with grade T, grade V and a significant negative correlation with growth activity. Our vast literature review on different signaling pathways in pterygium showed that EMT has centralization role in recurrence of this disease. Our data confirmed that EMT is important in the recurrence of pterygium samples and different signaling pathways end up activating the EMT markers. It is suggested to evaluate the environmental factors and their correlation with molecular markers to select favorable treatment for this kind of diseases.

Barriers between community screening for visual problems and treatments in a tertiary center.

OBJECTIVE: To evaluate the effectiveness of mobile ophthalmic unit screenings and to investigate barriers between community care and resolution of the problem at a tertiary center. METHODS: This prospective study evaluated a convenience sample from 10 municipalities in São Paulo State, Brazil. Patients were assessed in the municipality by a mobile ophthalmic unit and underwent a complete ophthalmic consultation. Patients were referred as warranted to a tertiary hospital. RESULTS: The mobile ophthalmic unit screened 1,928 individuals and 714 (37%) were referred. The mean age of the referred patients was 57.12 (SD = 19.5) years with best corrected visual acuity of 0.37 (SD = 0.36) logMAR. Forty-seven (6.6%) patients were blind and 185 (26.5%) were visually impaired. Cataracts (44.7%) and pterygium (14.7%) accounted for most referrals. Of those referred, 67.1% presented to the tertiary center. The diagnosis by the mobile ophthalmic unit corresponded to the one by the tertiary center in 88.5% of the cases. There were a significantly higher number of blind and visually impaired persons among those who presented to the hospital. There was a significantly greater attendance among patients living in more distant municipalities from the reference center with a higher number of inhabitants and a greater number of ophthalmologists in the cities of origin (p < 0.05, all comparisons). Complete treatment was performed in 65.6% of patients, and loss to follow-up was the main cause of incomplete treatment in 50.7% of patients. A total of 313 cataract surgeries were performed, which reduced the number of blind patients from 20 to 2 and of visually impaired individuals from 87 to 2 (p < 0.001). CONCLUSIONS: Only 37% of the patients assessed by a mobile ophthalmic unit required referral to a tertiary hospital. Among the referred patients, 67.1% presented to the hospital, and complete resolution after treatment was approximately 65.5%. There was a significant improvement in visual acuity and a reduction in the prevalence of blindness and visual impairment postoperatively.

Adjuvant Use of Cyclosporine A in the Treatment of Primary Pterygium: A Systematic Review and Meta-Analysis.

PURPOSE: To evaluate the efficacy and tolerability of cyclosporine A (CsA) as an adjuvant treatment for primary pterygium. METHODS: A comprehensive literature search from 7 databases (EMBASE, ISI Web of Science, PubMed, and the Cochrane Library for studies published in English and VIP, Wan Fang, and CNKI for studies published in Chinese). For the recurrence rate, pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effects model. Tolerability estimates were measured by OR for adverse events. RESULTS: A total of 7 studies meeting the inclusion criteria were included in this meta-analysis. Compared with the group with adjunctive CsA usage, the control group (no adjuvant use of CsA) showed a significantly increased risk of pterygium recurrence (OR = 2.71; 95% CI, 1.62-4.54). No obvious heterogeneity was detected in the included studies. Subgroup analysis showed that adjuvant use of CsA with pterygium excision alone resulted in a significantly lower frequency of recurrence than was seen in the group without adjuvant use of CsA (OR = 3.16; 95% CI, 1.18-8.84). However, there is no significant difference in pterygium recurrence between the subgroup (CsA + pterygium excision + limbal conjunctival autograft or flap rotation) and the subgroup without adjunctive CsA usage (pterygium excision + limbal conjunctival autograft or flap rotation). CONCLUSIONS: This meta-analysis suggests that adjuvant use of CsA can significantly reduce the risk of pterygium recurrence compared with pterygium excision alone, whereas adjuvant use of CsA may not reduce the risk of pterygium recurrence in terms of pterygium excision + limbal conjunctival autograft or conjunctival flap rotation.

Bayesian multivariate meta-analysis of multiple factors.

In medical sciences, a disease condition is typically associated with multiple risk and protective factors. Although many studies report results of multiple factors, nearly all meta-analyses separately synthesize the association between each factor and the disease condition of interest. The collected studies usually report different subsets of factors, and the results from separate analyses on multiple factors may not be comparable because each analysis may use different subpopulation. This may impact on selecting most important factors to design a multifactor intervention program. This article proposes a new concept, multivariate meta-analysis of multiple factors (MVMA-MF), to synthesize all available factors simultaneously. By borrowing information across factors, MVMA-MF can improve statistical efficiency and reduce biases compared with separate analyses when factors were missing not at random. As within-study correlations between factors are commonly unavailable from published articles, we use a Bayesian hybrid model to perform MVMA-MF, which effectively accounts for both within- and between-study correlations. The performance of MVMA-MF and the conventional methods are compared using simulations and an application to a pterygium dataset consisting of 29 studies on 8 risk factors.

Barriers between community screening for visual problems and treatments in a tertiary center

ABSTRACT OBJECTIVE To evaluate the effectiveness of mobile ophthalmic unit screenings and to investigate barriers between community care and resolution of the problem at a tertiary center. METHODS This prospective study evaluated a convenience sample from 10 municipalities in São Paulo State, Brazil. Patients were assessed in the municipality by a mobile ophthalmic unit and underwent a complete ophthalmic consultation. Patients were referred as warranted to a tertiary hospital. RESULTS The mobile ophthalmic unit screened 1,928 individuals and 714 (37%) were referred. The mean age of the referred patients was 57.12 (SD = 19.5) years with best corrected visual acuity of 0.37 (SD = 0.36) logMAR. Forty-seven (6.6%) patients were blind and 185 (26.5%) were visually impaired. Cataracts (44.7%) and pterygium (14.7%) accounted for most referrals. Of those referred, 67.1% presented to the tertiary center. The diagnosis by the mobile ophthalmic unit corresponded to the one by the tertiary center in 88.5% of the cases. There were a significantly higher number of blind and visually impaired persons among those who presented to the hospital. There was a significantly greater attendance among patients living in more distant municipalities from the reference center with a higher number of inhabitants and a greater number of ophthalmologists in the cities of origin (p < 0.05, all comparisons). Complete treatment was performed in 65.6% of patients, and loss to follow-up was the main cause of incomplete treatment in 50.7% of patients. A total of 313 cataract surgeries were performed, which reduced the number of blind patients from 20 to 2 and of visually impaired individuals from 87 to 2 (p < 0.001). CONCLUSIONS Only 37% of the patients assessed by a mobile ophthalmic unit required referral to a tertiary hospital. Among the referred patients, 67.1% presented to the hospital, and complete resolution after treatment was approximately 65.5%. There was a significant improvement in visual acuity and a reduction in the prevalence of blindness and visual impairment postoperatively.

[Pterygium: etiology, pathogenesis, treatment]. / Pterigium: étiologiia, patogenez, lechenie.

Pterygium is a degenerative condition characterized by fibrovascular outgrowth of conjunctiva over the cornea. Many theories exist that try to explain its pathogenesis. The current belief is that this disease is multifactorial with ultraviolet radiation being the most important trigger. Attention is also paid to such factors as tear film changes, cytokines and growth factors disbalance, immunologic disturbances, genetic mutations, and viral infections. Modern classifications consider the rate of fibrovascular growth, its progressive potential, and histological features. In the beginning pterygium is usually asymptomatic, however, dry eye manifestations may be present, such as burning, itching, and/or tearing. As the lesion grows toward the optical zone, visual acuity gets compromised, and thus, surgical treatment is required. Because of recurrences and repeated surgeries, the growth of the lesion may become more aggressive and cause irregular astigmatism. Comprehensive surgery of pterygium is aimed at not only removing the lesion, but also preventing recurrences. Advisable are modified bare sclera techniques with subsequent transposition of the conjunctival flap, conjunctival autotransplantation, amniotic membrane transplantation, and peripheral lamellar keratoplasty (in cases of significant ingrowth). In some cases, antirecurrent adjuvant therapy may be considered that involves the use of mitomycin C, 5-fluoruracil, and VEGF inhibitors. However, the search for the best treatment for pterygium, i.e. an easy to perform, cosmetically-friendly method associated with minimal risk of recurrences and/or complications, remains an interest of modern ophthalmology.

Cultivation and characterization of pterygium as an ex vivo study model for disease and therapy.

PURPOSE: Development of ex vivo model to study pathogenesis, inflammation and treatment modalities for pterygium. METHODS: Pterygium obtained from surgery was cultivated (3 months). Gravitational attachment method using viscoelastic facilitated adherence of graft and outgrowing cells. Medium contained serum as the only growth supplement with no use of scaffolds. Surface profiling of the multi-layered cells for hematopoietic- and mesenchymal stem cell markers was performed. Examination of cells by immunohistochemistry using pluripotency, oxidative stress, stemness, migration and proliferation, epithelial and secretory markers was performed. The effect of anti-proliferative agent Mitomycin C upon secretion of pro-inflammatory cytokines IL-6 and IL-8 was assessed. RESULTS: Cells showed high expression of migration- (CXCR4), secretory- (MUC1, MUC4) and oxidative damage- (8-OHdG) markers, and low expression of hypoxia- (HIF-1α) and proliferation- (Ki-67) markers. Moderate and low expression of the pluripotency markers (Vimentin and ΔNp63) was present, respectively, while the putative markers of stemness (Sox2, Oct4, ABCG-2) and epithelial cell markers- (CK19, CK8-18) were weak. The surface marker profile of the outgrowing cells revealed high expression of the hematopoietic marker CD47, mesenchymal markers CD90 and CD73, minor or less positivity for the hematopoietic marker CD34, mesenchymal marker CD105, progenitor marker CD117 and attachment protein markers while low levels of IL-6 and IL-8 secretion ex vivo, were inhibited upon Mitomycin C treatment. CONCLUSION: Ex vivo tissue engineered pterygium consists of a mixture of cells of different lineage origin, suitable for use as a disease model for studying pathogenesis ex vivo, while opening possibilities for new treatment and prevention modalities.

Developments and current approaches in the treatment of pterygium.

PURPOSE: To assess and compare the studies conducted in the literature with recurrence rates and the summary of the justified treatment approaches be presented. METHOD: Pterygium, a fibrovascular tissue that proceeds from the bulbar conjunctiva towards the cornea, is quite a commonly seen ocular surface deterioration. The treatment is performed through a surgical excision, and the frequent recurrence of this disorder, despite the developments of today, is the major problem experienced in the wake of the surgery. There are various treatment methods applied for the prevention of recurrence; yet, there is no definite view as to what treatment is the most effective one. Since the recurrent pterygium cases are more aggressive than the primary pterygium, it is of great importance to determine the treatment method in which recurrence rate is the lowest. In different studies seen in the literature, there is difficulty in comparing the results due to the fact that the follow-up periods, recurrence criteria and the doses and durations of the medications administered differ from one another. CONCLUSION: When the literature is reviewed, the bare sclera technique is not used due to the high rate of recurrence, whereas successful results can be achieved through the conjunctival autograft technique. Lower recurrence rates have been reported along with the administration of mitomycin C, 5-FU and other agents that were used as an adjuvant treatment.

Parche escleral en manejo de escleritis necrosante con inflamación. Informe de un caso / Scleral patch graft in the management of necrotising scleritis with inflammation. A case report

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5-Fluorouracil vs avastin as adjunct to conjunctival autograft in the surgical treatment of pterygium.

BACKGROUND: The use of adjunct antimetabolite therapy along with conjunctiva autograft has been shown to be effective in preventing pterygium recurrence. There has however been fewer reports on the effect of anti-vascular endothelial growth factor on pterygium recurrence. OBJECTIVE: To compare 5-fluorouracil with conjunctival autograft with bevacizumab (avastin) used along with autograft in the surgical treatment of pterygium. METHODS: A randomized controlled prospective study of outcome of pterygium treatment using 5-fluorouracil with conjunctiva autograft as adjuvant treatment compared avastin with conjunctiva autograft. RESULTS: A total of 70 eyes of 70 patients were recruited into the study with a mean age of 51.49 (±14.36) years. Thirty-five patients each were randomized into the 5-fluorouracil treatment group and into the avastin treatment group respectively. The mean follow-up was 18.35 months (18.44 for the 5-FU and 18.26 for the avastin group). Post operative, pterygium recurrence was observed in 1/27 (3.7%) eyes treated with 5-fluorouracil and 1/26 (3.9%) eyes of the avastin group. Both recurrences were observed at 1 year of follow-up and they were both female patients aged 46 and 52 years, respectively. CONCLUSIONS: Both 5-fluorouracil and avastin are comparably effective as adjunct to conjunctival autograft. However, cost, availability, and convenience are other considerations with use of avastin.

A randomized controlled prospective study to assess the role of subconjunctival bevacizumab in primary pterygium surgery in Indian patients.

BACKGROUND: Pterygium is an ocular surface disorder with prevalence rates ranges from 0.3% to 29% in different parts of the world. Vascular endothelial growth factor (VEGF) has been detected in increased amounts in pterygium epithelium, compared with normal conjunctiva. Bevacizumab is a recombinant, humanized anti-VEGF antibody suggested as a possible adjunctive therapy for pterygium excision that appears to have a role in prevention of recurrence. We conducted this study to evaluate the role of subconjunctival bevacizumab in primary pterygium surgery in Indian patients. METHODS: In this randomized prospective clinical study, the patients were randomized into two groups of 30 patients each. Study group received 1.25 mg/0.05 ml subconjunctival bevacizumab 1 week before pterygium surgery with conjunctival autograft. Control group received 1.25 mg (0.05 ml) subconjunctival normal saline 1 week prior to pterygium surgery with conjunctival autograft. Patients were followed up at day 1, day 7, 1 month and 3 months. The main outcome measures were morphology of pterygium after injection, intra-operative ease, recurrence of pterygia, and any complications. RESULTS: After giving bevacizumab, there was statistically significant improvement in grade, color intensity, size of pterygium, and symptoms of patients. Intra-operatively, less bleeding was observed by the surgeon. No statistically significant difference regarding reduction in astigmatism, improvement of visual acuity, and complications were observed in two groups. Recurrence was noted in five patients (8.33%) in total study population at the end of 3 months. It was present in two patients (6.67%) in Group A and three patients (10%) in Group B. CONCLUSION: Single preoperative administration of subconjunctival injection bevacizumab given 1 week before the pterygium excision with conjunctival autograft decreases the vascularity of newly formed blood vessels, hence may decrease recurrence rate though not in our study.

Monitoring corneal densities following primary pterygium excision with adjuvant topical mitomycin-C application--an observational study of corneal scar changes.

PURPOSE: Corneal densitometry is an inherent feature of the Pentacam device. We aim to assess the changes in corneal scar density with serial Scheimpflug images following primary pterygium excision with topical application of mitomycin-C. METHODS: We recruited patients who underwent primary, single-headed pterygium excision with topical adjuvant mitomycin-C. Scheimpflug images were taken at postoperative weeks 1, 4, and 12, and all patients received topical corticosteroid and antibiotic treatment for at least 4 weeks postoperatively. Corneal scar densities were generated by the software for analysis. Secondary outcome measures included intraocular pressures and pterygium recurrence at the end of 12 weeks. Changes in corneal densities between weeks 12, 4, and 1 were calculated. RESULTS: We recruited 31 eyes of 31 patients, of whom 16 were male patients and 15 were female patients, with 19 left and 12 right eyes. Mean age at operation was 62.0 ± 9.4 years. Mean reduction in density of the anterior 120 µm of cornea was -3.07 [95% confidence interval (CI), -6.600 to 0.460] and -3.455 (95% CI, -6.787 to -0.122) at postoperative 4 and 12 weeks, respectively, and mean reduction percentage was -4.7% (95% CI, -10.7% to 1.3%) and -6.3% (95% CI, -11.8% to -0.7%), respectively. No steroid response or pterygium recurrence was reported. CONCLUSIONS: Corneal densitometry is an objective measure to detect scar changes in zones and layers. The overall reduction of density was evident at 12 weeks postoperatively. These results might serve as baseline figures for future studies in assessing modulation of corneal scars over time.

Randomized trial comparing multilayer amniotic membrane transplantation with scleral and corneal grafts for the treatment of scleral thinning after pterygium surgery associated with beta therapy.

PURPOSE: The aim of this study was to compare the use of multilayer amniotic membrane transplantation (AMT) with lamellar corneal transplantation (LCT) and lamellar scleral transplantation (LST) for the treatment of scleral thinning after pterygium surgery associated with beta therapy. METHODS: Twenty-six eyes from 26 different patients with scleral thinning as a consequence of beta therapy after pterygium surgery were evaluated at the Federal University of São Paulo, Brazil. Ophthalmologic examination and ultrasound biomicroscopy were performed to assess scleral thinning before the transplant surgery and then repeated at 30, 90, and 180 days after surgery. An increase in scleral thickness, epithelialization of the ocular surface, and preservation of the ocular globe were the main outcome measures. RESULTS: Irrespective of the surgical technique used (AMT, LCT, or LST), no clinical or statistical changes in corrected distance visual acuity were found in any of the patients during this study. The median preoperative scleral thickness was similar in all 3 groups: AMT = 0.45 mm, LST = 0.48 mm, and LCT = 0.52 mm (P = 0.257); however, 6 months after surgery, the median thickness in the AMT group (0.19) was significantly less than that of the LCT group (0.57) (P = 0.27) or the LST group (0.76) (P = 0.19). Epithelialization occurred in all the patients. CONCLUSIONS: LCT was the best option for the structural treatment of scleral thinning, followed by LST with a conjunctival flap. A high rate of reabsorption was found with AMT, which was the least effective of the 3 therapeutic options and should not be used for this condition.

S100A proteins as molecular targets in the ocular surface inflammatory diseases.

The S100 proteins are calcium-binding proteins that are exclusively expressed in vertebrates, where they interact with enzymes, cytoskeletal proteins, receptors, transcription factors, and nucleic acids to regulate proliferation, differentiation, apoptosis, inflammation, cell migration, energy metabolism, and Ca(2+) homeostasis. In this review, we focus on the S100A8 and S100A9 members of the family that are involved in the regulation of neutrophil chemotaxis and inflammation related to ocular surface diseases such as dry eye, meibomian gland dysfunction, pterygium, and corneal neovascularization. In our previous studies, we have found that the levels of S100A8 and S100A9 were elevated in these inflammatory ocular diseases. For instance, S100A8 and A9 were found to be upregulated in pterygium tissues at both transcript and protein levels. These findings are consistent with the role of S100A8 and S100A9 proteins in activating the innate immune system in the eye via Toll-like receptors (TLRs) and altering the immune tolerance of the eye-associated lymphoid system. Recently, use of S100A8-targeting antibody has shown promising results in targeting corneal neovascularization. Injection of S100A8 has been shown to inhibit eosinophilic infiltration and thus may have potential therapeutic implications in allergic diseases.