The role of HPV in the etiopathogenesis of pterygium and the relationship with recurrence.

PURPOSE: The primary aim of this study was to determine the prevalence of HPV in pterygium with polymerase chain reaction (PCR) testing and to investigate the relationship with clinicopathological factors. A secondary aim was to evaluate the relationship between HPV and the recurrence of pterygium. METHODS: The study included 60 patients. PCR analysis was used to determine the presence of HPV. All the patients were followed up in respect of the development of recurrence. Analyses were performed of patient age, pterygium site, specimen and pterygium size, histopathological findings, HPV status, operation technique and postoperative follow-up findings. In the HPV-positive patients, the relationship between HPV subtypes and other factors was evaluated. To determine the risk factors affecting recurrence rates, multivariate Cox regression analysis was applied subsequent to univariate analysis. In the Cox regression model, HPV status, age, sex, specimen size, size and site of pterygium were included among factors that may affect recurrences rates. RESULTS: Of the total 60 patients, the HPV-PCR test result could not be analysed in 14 because of an insufficient sample. Of the 46 patients with sufficient material for HPV-PCR analysis, the HPV-PCR result was positive in 15 (32.6%). The HPV subtype most often determined was type 16. No statistically significant relationship was determined between HPV positivity and HPV subtype and age or sex. Recurrence was determined in 10% of all the patients. Of the cases determined with recurrence, 66.7% were HPV positive. According to Kaplan-Meier analysis, the recurrence rates in HPV-positive and HPV-negative patients were 26.7% and 6.5%, respectively. A statistically significant difference was found between two groups in terms of recurrence rates (p: 0.046). According to the results of multivariate Cox regression analysis, though not statistically significant, the risk of recurrence was increased 6.18 times in HPV-positive patients with pterygium compared to HPV-negative ones. CONCLUSION: HPV infection may have a role in the development of pterygium and recurrence, but may not be sufficient alone. HPV probably has a role in the development of pterygium by acting together with several co-factors in the multi-stage process.

[Transplantation of the Bowman's layer in combined treatment of recurrent pterygium]. / Transplantatsiya boumenova sloya v kombinirovannom lechenii retsidiviruyushchego pterigiuma.

Pterygium is among the most frequent indications for extraocular ophthalmic surgery. The main method of pterygium treatment - its excision - is often combined with transplantation, non-transplantation, medication and other methods. However, the frequency of pterygium recurrence can exceed 35%, and the cosmetic and refraction outcomes satisfy neither the patient, nor the surgeon. PURPOSE: The study analyses the technical capability and feasibility for transplantation of the Bowman's layer in the treatment of recurrent pterygium. MATERIAL AND METHODS: The transplantation of the Bowmen's layer was performed according to the developed technique on 7 eyes with recurrent pterygium (7 patients aged 34 to 63 years). The combined surgery technique consisted of pterygium resection, laser ablation, autoconjunctival plasty, exposure to a cytostatic drug, non-suture transplantation of the Bowman's layer. Maximum length of the follow-up was 36 months. Analysis involved data from refractometry, visometry (without correction and with spectacle correction), and optical coherence tomography of the retina. RESULTS: There were no complications in any of the studied cases. The cornea and the transplant retained transparency throughout the entire follow-up duration. 36 months after surgery mean spectacle-corrected visual acuity amounted to 0.86±0.2, topographic astigmatism - 1.48±1.4 diopters. Recurrence of pterygium was not observed. All patients were satisfied with the cosmetic outcomes of the treatment. CONCLUSION: Non-suture transplantation of the Bowmen's layer recovers normal anatomy, physiology and transparency of the cornea after repeat surgical intervention for pterygium. No pterygium recurrences were observed throughout the entire follow-up after treatment with the proposed combined technique.

Prevalence and associated factors for pterygium in a Chinese rural population with type 2 diabetes in a cross-sectional study: Jiangsu Diabetic Eye Disease Study (JDEDS).

PURPOSE: To investigate the pterygium prevalence and evaluate risk factors of pterygium in rural type 2 diabetic (D2M) patients aged 50 years and above in Funing Country, Jiangsu Province, China. METHODS: A cross-sectional ophthalmic survey was conducted in type 2 diabetes mellitus (D2M) patients aged ≥ 50 years in Funing County, Jiangsu Province, China, which was named Jiangsu Diabetic Eye Disease Study (JDEDS). All participants underwent a comprehensive questionnaire and ocular examination. Pterygium was diagnosed by slit lamp examination. The risk factors associated with pterygium were evaluated with logistic regression models. RESULTS: The prevalence of pterygium was 22.37% (n = 427) and 95% confidence interval (CI) (20.50-24.24%) in D2M patients aged 50 years and above in JDEDS. The prevalence of pterygium was 18.32% (95% CI 15.33-21.32%) in men and 24.43% (95% CI 22.06-26.80%) in women. Women had a higher prevalence than men (p = 0.001). Multivariate analysis showed, for male participants with D2M, pterygium was independently associated with increasing age [70-79 years: OR and 95% CI 2.49(1.20-5.18), p = 0.014; ≥ 80 years: 4.84(2.04-11.47), p < 0.001], while cigarette smoking was the protective factors, especially in current smoker [OR and 95% CI 0.79(0.67-0.92); p = 0.003]. For female participants with D2M, age [60-69 years OR and 95% CI 1.68(1.07-2.62), p = 0.023; 70-79 years: 2.62(1.69-4.06), p < 0.001; ≥ 80 years:3.24(1.70-5.90), p < 0.001], hypertension [OR and 95% CI 1.40(1.05-1.87), p = 0.024], BMI 24-27.9 [OR and 95% CI 1.20(1.00-1.44), p = 0.047], higher HbA1c [(5.6-7.9) % OR and 95% CI 1.42(1.10-1.82), p = 0.006; (8.0-9.9) %: 1.32(1.10-1.58), p = 0.003] were risk factors. CONCLUSIONS: D2M patients aged over 50 years has a high prevalence of pterygium in JDEDS. The pterygium prevalence is higher in female D2M participants. Diabetes and related factors may be risk factors of pterygium in female D2M patients. Further studies are needed to explore the gender difference in the pathogenesis of pterygium in D2M subjects.

Consecutive dosing of UVB irradiation induces loss of ABCB5 expression and activation of EMT and fibrosis proteins in limbal epithelial cells similar to pterygium epithelium.

Pterygium pathogenesis is often attributed to a population of altered limbal stem cells, which initiate corneal invasion and drive the hyperproliferation and fibrosis associated with the disease. These cells are thought to undergo epithelial to mesenchymal transition (EMT) and to contribute to subepithelial stromal fibrosis. In this study, the presence of the novel limbal stem cell marker ABCB5 in clusters of basal epithelial pterygium cells co-expressing with P63α and P40 is reported. ABCB5-positive pterygium cells also express EMT-associated fibrosis markers including vimentin and α-SMA while their ß-catenin expression is reduced. By using a novel in vitro model of two-dose UV-induced EMT activation on limbal epithelial cells, we could observe the dysregulation of EMT-related proteins including an increase of vimentin and α-SMA as well as downregulation of ß-catenin in epithelial cells correlating to downregulation of ABCB5. The sequential irradiation of limbal fibroblasts also induced an increase in vimentin and α-SMA. Taken together, these data demonstrate for the first time the expression of ABCB5 in pterygium stem cell activity and EMT-related events while the involvement of limbal stem cells in pterygium pathogenesis is exhibited via sequential irradiation of limbal epithelial cells. The later in vitro approach can be used to further study the involvement of limbal epithelium UV-induced EMT in pterygium pathogenesis and help identify novel treatments against pterygium growth and recurrence.

Ocular health among industrial workers: a prevalence study of foreign body injury, refractive error, dry eye, pterygium and pingueculae.

BACKGROUND: Workplaces play a critical role in developing ocular diseases, owing to the risk of accidents. This study aimed to evaluate the ocular health of industrial workers by determining the prevalence of foreign body injury, refractive error, dry eye, and pterygium/pingueculae, as well as the factors influencing these diseases. METHODS: This study involved on-site examinations of workers from an industrial area hosting marble processing factories and metal sectors. Data such as refractive error, foreign body injury-related corneal nephelium, pterygium/pingueculae presence, and Schirmer test-assisted dry eye evaluation were all collected. RESULTS: The average age of workers was 35.78±10.05 years, with a female-to-male ratio of 20:220. The majority of workers had completed primary school (56.3%), smoked >1 cigarette/day (57.6%), and did not use any assistive devices for bodily functions (88.3%). On average, working hours/week were 55.07±8.79, and working years were 5.99±7.00. Dry eyes were found in 31 (22%), and 35 (34%) marble and metal workers, respectively (p=0.042). 11 (7.9%) marble workers and 29 (28%) metal workers had foreign body ocular injury-related corneal nephelium (p=0.0001). Furthermore, pterygium/pingueculae were revealed in 17 marble workers (12.3%) and three metal workers (3%) (p=0.009). CONCLUSIONS: Ocular health is essential, and routine ocular health screening in industrial workers, as well as workplace safety measures, should be implemented to prevent potential occupational accidents.

The association of sun exposure, ultraviolet radiation effects and other risk factors for pterygium (the SURE RISK for pterygium study) in geographically diverse adult (≥40 years) rural populations of India -3rd report of the ICMR-EYE SEE study group.

PURPOSE: To determine the prevalence and risk factors for pterygium in geographically diverse regions of India. METHODS: A population-based, cross-sectional multicentric study was conducted in adults aged ≥40 years in plains, hilly and coastal regions of India. All participants underwent a detailed questionnaire-based assessment for sun exposure, usage of sun protective measures, exposure to indoor smoke, and smoking. Detailed ocular and systemic examinations were performed. Pterygium was diagnosed and graded clinically by slit-lamp examination. Association of pterygium with sociodemographic, ophthalmological, and systemic parameters was assessed. Physical environmental parameters for the study period were estimated. RESULTS: Of the 12,021 eligible subjects, 9735 (81% response rate) participated in the study. The prevalence of pterygium in any eye was 13.2% (95% CI: 12.5%-13.9%), and bilateral pterygium was 6.7% (95% CI: 6.2-7.2). The prevalence increased with age (<0.001) irrespective of sex and was highest in those aged 60-69 years (15.8%). The prevalence was highest in coastal (20.3%), followed by plains (11.2%) and hilly regions (9.1%). On multi-logistic regression, pterygium was positively associated with coastal location (P<0.001), illiteracy (P = 0.037), increasing lifetime sun exposure (P<0.001), and negatively associated with BMI ≥25 kg/m2 (P = 0.009). CONCLUSION: Pterygium prevalence is high in the rural Indian population. The association of pterygium with several potentially modifiable risk factors reflects its multifactorial etiology and provides targets for preventive measures.

[Conjunctival Degeneration and Neoplasia]. / Bindehautdegenerationen und -neoplasien.

Conjunctival tumors result from gain of tissue, which can be either degenerative or neoplastic, but also inflammatory. In this article, degenerative (pterygium and pinguecula) as well as benign and malignant neoplastic conjunctival changes (epithelial, melanocytic and vascular tumors, choristomas as well as metastases) are discussed with regard to pathogenesis, symptoms, diagnostics and current status of treatment.

Expression of p16 in pterygium and its relation with epithelial dysplasia and possible etiologic role of HPV.

Context: p16 is an important tumor suppressor gene and responsible for regulating the cell cycle. Diffuse positivity with p16 in the cervix and head/neck carcinomas can be regarded as a surrogate marker of the presence of high-risk human papillomavirus (HPV). Aim: The aim of our study was to search the existence of p16 expression in pterygium. We also analyzed the association of p16 expression with epithelial dysplasia and HPV expression. Subjects and Methods: The study enrolled 75 cases of pterygium. The conjunctival tissues of 10 patients excised by the strabismus surgery were used as control group. All of the slides were stained with p16 via the immunohistochemical method. Results: 49 (65%) of pterygiums showed low-grade epithelial dysplasia. None of the control groups showed dysplasia. Positive expression of p16 in patient group was significantly higher (P < 0.001). Staining percentage (SP) of p16 was between 0 and 26% in pterygium; mean SP was 5.1%. There was no staining in the control group. A total of 59 (72%) pterygium cases were positive with p16. Appoximately 42 of 49 (85%) cases with dysplasia showed p16 staining. There was a significant relation between dysplasia and positive expression of p16 (P < 0.001). Conclusions: P16 is significantly expressed in pterygium and correlated with epithelial dysplasia. Furthermore, the existence of p16 expression suggests that HPV is a possible ethiological factor in pterygium. We think that examination of p16 expression and analysis of HPV DNA in p16 positive cases can help us to understand the etiopathogenesis of the disease better.

Exérese de pterígio em paciente pós-LASIK com técnica de air bubble / Pterygium surgery with air bubble technique in a post-LASIK patient

RESUMO O pterígio é uma das doenças que mais acomete a superfície ocular, principalmente em regiões próximas ao Equador. Ocorre principalmente em adultos jovens, podendo ocasionar sintomas, danos estéticos e ópticos. Relata-se um caso de exérese de pterígio classificado pela extensão corneana em grau II e, pela vascularização, em grau 2 de Tan, com cirurgia prévia de LASIK, a partir de uma nova técnica, a técnica de Moscovici, a qual fundamenta-se na dissecção com bolha de ar, com a finalidade de separar o epitélio conjuntival do estroma profundo e da Tenon, com maior facilidade e rapidez e para obter enxertos finos.

ABSTRACT Pterygium is one of the diseases that most affect the ocular surface, especially in regions close to the equator. It mainly affects young adults and can cause symptoms, as well as aesthetic and optical impairment. We report a case of pterygium excision classified by grade II corneal extension and Tan grade 2 vascularization with previous laser in situ keratomileusis (LASIK) surgery, using a new technique, the Moscovici technique, which is based on dissection with an air bubble to separate easier and faster the conjunctival epithelium from the deep stroma and the Tenon, obtaining thinner grafts.

Conjunctival Expression of Toll-Like Receptor 3 Plays a Pathogenic Role in the Formation of Ultraviolet Light-Induced Pterygium.

Purpose: Toll-like receptor 3 (TLR3), as a damage-associated molecular pattern sensor, can detect self-RNA released from necrotic cells induced by ultraviolet B (UVB) radiation exposure. Pterygium formation is believed to be a tumorigenesis-like process induced by UVB exposure. In this study, we aimed to investigate the expression pattern of TLR3 in pterygium specimens and cultured pterygial epithelial cells (PECs). Methods: Human pterygium and ipsilateral pterygium-free conjunctiva from the same patients were used in this study. The expression of TLR3 and nuclear factor-kappa B (NF-κB) was investigated in these specimens. PECs were exposed to UVB radiation to determine the effect of UVB on the expression of TLR3 and the activation of NF-κB. Results: The immunofluorescence study showed stronger TLR3 expression in superficial epithelial cells in the pterygial epithelium in comparison with the normal conjunctival epithelium. The expression of TLR3 decreased in intensity from the superficial epithelium toward the basal cell layer, implying a correlation between UVB exposure and TLR3 expression. Differential TLR3 expression patterns in pterygial and conjunctival tissues were also found in quantitative PCR analyses. PECs after UVB irradiation had higher protein levels of TLR3 and phospho-NF-κB than those of the PECs without irradiation. Immunofluorescence studies showed that UVB irradiation induced the nuclear translocation of NF-κB in the PECs. In PECs with the targeted TLR3 gene silencing, the expression of phospho-NF-κB was not induced by UVB irradiation. Conclusions: Our results indicate that UVB exposure, TLR3 expression, and NF-κB activation may be a critical sequence that leads to the formation of pterygium.

Pterygium in Onitsha, Nigeria.

OBJECTIVE: To determine the pattern and risk factors of pterygium in adults at the Guinness Eye Centre Onitsha, Nigeria. MATERIALS AND METHODS: Consecutive adults aged ≥30 years with pterygium were studied. Each patient had comprehensive ocular examination including visual acuity, anterior segment, and adnexal assessment and fundoscopy. The pterygium was graded in terms of severity and type. RESULTS: A total of 156 patients with pterygium participated; 92 (59%) females versus 64 (41%) males (F:M =3:2). The age range was 30-65 years; mean: 43.9 ± 8.4 years. The majority of the study population (36.5%) was of the age group 40-49 years. The subjects were predominately traders 78 (50%) and 93 (59.6%) of the pterygium patients were outdoor workers. Bivariate analysis indicated that those involved in outdoor work were six times at greater risk of developing pterygium than indoor workers (P = 0.001; OR = 6.2). Out of the 156 pterygium patients seen, 107 (68.6%) of them complained of associated symptoms. Redness of the eye was the commonest symptom reported by 79 (50.9%) cases while 8 (5.1%) cases complained of burning sensation. There was a preponderance of nasal pterygia with temporal pterygia being the least. Blinding pterygium was seen in three eyes (1.3%). CONCLUSION: Pterygium is a common disorder presenting at eye clinics. Outdoor workers are at a greater risk of developing pterygium. Thus, health education is of great importance.

Association among pterygium, cataracts, and cumulative ocular ultraviolet exposure: A cross-sectional study in Han people in China and Taiwan.

PURPOSE: Pterygium is an ocular surface disorder mainly caused by ultraviolet (UV) light exposure. This study explored the relationships between six cataract types with pterygium and UV exposure. METHODS: We have previously studied cataracts in residents of three regions in China and Taiwan with different UV intensities. From that study, we identified 1,547 subjects with information on the presence or absence of pterygium. Pterygium severity was graded by corneal progress rate. Cataracts were graded by classification systems as three main types (cortical, nuclear, posterior subcapsular) and three subtypes (retrodots, waterclefts, fiber folds) with high prevalence in middle-aged and elderly people. We calculated the cumulative ocular UV exposure (COUV) based on subject data and National Aeronautics and Space Administration data on UV intensities and used logistic regression to calculate odds ratios for the associations of COUV, cataract, and pterygium. RESULTS: We found an overall pterygium prevalence of 23.3%, with significant variation among the three regions. Four cataract types (cortical, nuclear, posterior subcapsular, and retrodots) were significantly associated with the presence of pterygium. CONCLUSIONS: There was a significant association between COUV and pterygium, indicating that COUV is associated with the risk of pterygium development and that pterygium is useful as an index of UV exposure. Furthermore, the type of cataract in eyes with pterygium may indicate the level of UV exposure.

Reproductive risk factors of pterygium in postmenopausal women: a nationwide study in the Republic of Korea.

This study is to elucidate the associations between female reproductive factors and pterygium. A total of 1,339,969 postmenopausal women in a retrospective cohort of Korean National Health Insurance Service data on ages 40 and above in 2009 was included. Cox proportional hazards regression was conducted to assess the hazard ratio (HR) for pterygium according to reproductive factors. Late menarche, early menopause, short reproductive period, increasing parity (≥ 2 children), breastfeeding (≥ 6 months), and no use of hormone replacement therapy (HRT) or oral contraceptive (OC) were significantly associated with risk of pterygium. In multivariate analysis, the HR for pterygium was 1.764 (95% confidence interval [CI], 1.529-2.035) for menarche age ≥ 17 years (reference: menarche age < 12 years). The HR of menopause age ≥ 55 years was 0.782 (95% CI, 0.724-0.845) (reference: menopause age < 40 years). The HR of parity ≥ 2 was 1.261 (95% CI, 1.148-1.385) (reference: nulliparity). The HR of breastfeeding ≥ 1 year was 1.663 (95% CI, 1.564-1.768) (reference: no breastfeeding). The HRs of HRT and OC use for any length of time were lower than those for the non-user groups (reference). Reproductive factors that increase estrogen exposure have protective effects against pterygium in females.

Pterigión dorsal y onicólisis asociados a un penfigoide ampolloso / Dorsal Pterygium and Onycholysis Associated With Bullous Pemphigoid

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Frequency of conjunctival epithelial dysplasia in patients with pterygium.

PURPOSE: To determine the frequency of ocular squamous surface neoplasia associated with pterygium in an ophthalmology reference center in Central Mexico. METHODS: We reviewed histopathological reports and slides of all patients who underwent pterygium surgery from 2014 to 2016 at the Instituto Mexicano de Oftalmologia in Queretaro (Mexico). RESULTS: We studied 177 biopsy samples; 66% were from women, and the median age was 52 years. We found ocular squamous surface neoplasias in 11.29% (n=20) of the samples. One biopsy sample revealed a poorly differentiated keratinizing and infiltrating carcinoma. CONCLUSIONS: The prevalence of ocular squamous surface neoplasia in our region appears to be high. Countrywide studies are necessary to determine the true prevalence of ocular squamous surface neoplasia in Mexico and to examine related risk factors.

Frequency of conjunctival epithelial dysplasia in patients with pterygium / Incidência de displasia do epitélio conjuntival em pacientes com diagnóstico de pterígio

ABSTRACT Purpose: To determine the frequency of ocular squamous surface neoplasia associated with pterygium in an ophthalmology reference center in Central Mexico. Methods: We reviewed histopathological reports and slides of all patients who underwent pterygium surgery from 2014 to 2016 at the Instituto Mexicano de Oftalmologia in Queretaro (Mexico). Results: We studied 177 biopsy samples; 66% were from women, and the median age was 52 years. We found ocular squamous surface neoplasias in 11.29% (n=20) of the samples. One biopsy sample revealed a poorly differentiated keratinizing and infiltrating carcinoma. Conclusions: The prevalence of ocular squamous surface neoplasia in our region appears to be high. Countrywide studies are necessary to determine the true prevalence of ocular squamous surface neoplasia in Mexico and to examine related risk factors.

RESUMO Objetivo: Determinar a frequência de neoplasia escamosa da superfície ocular associada ao pterígio com apresentação clínica, em um centro de referência em Oftalmologia da região central do México. Métodos: Revisamos os laudos histopatológicos e as lâminas de biópsia de todos os pacientes que foram submetidos à cirurgia de pterígio de 2014 a 2016 no Instituto Mexicano de Oftalmologia, na cidade de Querétaro. Resultados: Estudamos 177 amostras de biópsia; 66% eram de pacientes do sexo feminino, sendo a mediana da idade de 52 anos. Encontramos neoplasia escamosa da superfície ocular em 11,29% (n=20). Uma amostra de biópsia mostrou um carcinoma queratinizante infiltrativo pouco diferenciado. Conclusões: A prevalência da neoplasia escamosa da superfície ocular nessa região parece ser maior do que a indicada por outras pesquisas. Mais estudos de âmbito nacional são necessários para determinar a verdadeira prevalência da neoplasia escamosa da superfície ocular no México e examinar os fatores de risco relacionados.

Optical Analysis and Reappraisal of the Peripheral Light Focusing Theory of Nasal Pterygia Formation.

Purpose: Pterygia are much more common nasally than temporally. Ultraviolet (UV) radiation is a major risk factor. Coroneo proposed that the nasal preference is caused by the "peripheral light focusing effect," (PLF), in which UV at an oblique angle passes through temporal cornea and is concentrated on and damages nasal limbal stem cells. This study evaluates whether the PLF is sufficient to explain the nasal preference. Methods: Whereas Coroneo and colleagues derived the maximum PLF intensity gain (UV concentration factor) as a function of incident angle (i.e., different nasal limbal positions were used for different incident angles) the current analysis derived intensity gain at a fixed position such at the nasal corneo-limbal junction (CLJ). This provided a measure of the total PLF irradiation at this position, which was compared to total direct irradiation of nasal and temporal limbus at the corresponding positions (e.g., CLJs). In Part 1, analysis was performed like that of Coroneo, using horizontally incident UV; in Part 2, the analysis was extended to include incident rays above and below the horizontal. Results: In both part 1 and part 2 of the study, the limbal UV irradiation of the nasal limbus from the PLF was not sufficient to explain the strong nasal location preference of pterygia. Conclusions: The analysis calls into question the PLF explanation of nasal location preference. Other explanations of the nasal preference, and of pterygium pathogenesis, should be considered, such as temporal to nasal tear flow carrying substances such as cytokines to the nasal limbus.