The role of anterior segment optical coherence tomography in the evaluation of the pterygium.

BACKGROUND: To evaluate the ability of anterior segment optical coherence tomography (AS-OCT) to visualize the anatomic features of the pterygium and its invasion of the corneal layers. METHODS: Seventy-five eyes of 54 patients diagnosed with pterygium were included. All subjects underwent complete ophthalmologic examinations, including AS-OCT. The limbus-apex distance, vertical height at the limbus, invasion of the Bowman's and stromal layers, and other morphologic structures of the pterygium tissue were analyzed. RESULTS: The mean age of the patients was 49.67 ± 16.49 (20-85) years. The mean apex-limbus distance was 2548.37 ± 1026.32 (933-4597) µm, and the mean vertical height at the limbus was 4843.89 ± 1374.10 (1740-7784) µm. A space was observed beneath the pterygium tissue in 44 (58.67%) eyes. The mean width and height of this space were 1756.33 ± 560.22 (1009-3095) µm and 231.70 ± 85.88 (109-465) µm, respectively. Invasion of the Bowman's layer was apparent in 74 (98.67%) eyes, and invasion of the stromal layer was detected in 33 (44%) eyes. A hyperreflective layer was observed beneath the epithelial layer at the edge of the pterygium apex in 31 (41.33%) eyes. In 24 (92.31%) of the 26 advanced pterygium cases and 20 (40.82%) of the 49 early pterygium cases, a subpterygium space was found beneath the lesion (p = 0.0001). CONCLUSION: AS-OCT enables measurement of the actual size and thickness of pterygia, assessment of invasion of the Bowman's and stromal layers of the cornea, and evaluation of the pterygium structure. Over half of the eyes exhibited space beneath the pterygium.

Prevalence of co-existent neoplasia in clinically diagnosed pterygia in a UK population.

INTRODUCTION: Ocular surface squamous neoplasia (OSSN) and pterygia share risk factors and co-exist in only a minority of cases. Reported rates of OSSN in specimens sent as pterygium for histopathological analysis vary between 0% and nearly 10%, with the highest rates reported in countries with high levels of ultraviolet light exposure. As there is a paucity of data in European populations, the aim of this study was to report the prevalence of co-existent OSSN or other neoplastic disease in clinically suspected pterygium specimens sent to a specialist ophthalmic pathology service in London, United Kingdom. METHODS: We performed a retrospective review of sequential histopathology records of patients with excised tissue submitted as suspected "pterygium" between 1997 and 2021. RESULTS: In total, 2061 specimens of pterygia were received during the 24-year period, with a prevalence of neoplasia in those specimens of 0.6% (n = 12). On detailed review of the medical records of these patients, half (n = 6) had the pre-operative clinical suspicion of possible OSSN. Of those cases without clinical suspicion pre-operatively, one was diagnosed with invasive squamous cell carcinoma of the conjunctiva. CONCLUSION: In this study, rates of unexpected diagnoses are reassuringly low. These results may challenge accepted dogma, and influence future guidance for the indications for submitting non-suspicious pterygia for histopathological analysis.

Effects of chemokine receptor CCR7 in the pathophysiology and clinical features of the immuno-inflammatory response in primary pterygium.

OBJECTIVE: Chemokine receptor 7 (CCR7) has been considered a critical biomarker in inflammation and the immune response; however, little is known about CCR7 in pterygia. This study aimed to investigate whether CCR7 participates in the pathogenesis of primary pterygia and how CCR7 affects the progression of pterygia. METHODS: This was an experimental study. Slip-lamp photographs of 85 pterygium patients were used to measure the width, extent, and area of pterygia with computer software. Pterygium blood vessels and general ocular redness were quantitatively analyzed with a specific algorithm. The expression of CCR7 and its ligands C-C motif ligand 19 (CCL19) and C-C motif ligand 21 (CCL21) in control conjunctivae and excised pterygia collected during surgery were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and immunofluorescence staining. The phenotype of CCR7-expressing cells was identified by costaining for major histocompatibility complex II (MHC II), CD11b or CD11c. RESULTS: The CCR7 level was significantly increased by 9.6-fold in pterygia compared with control conjunctivae (p = 0.008). The higher the expression of CCR7 was, the more blood vessels appeared in pterygia (r = 0.437, p = 0.002) and the more general ocular redness was (r = 0.51, p < 0.001) in pterygium patients. CCR7 was significantly associated with pterygium extent (r = 0.286, p = 0.048). In addition, we found that CCR7 colocalized with CD11b, CD11c or MHC II in dendritic cells, and immunofluorescence staining showed that CCR7-CCL21 is a potential chemokine axis in pterygium. CONCLUSIONS: This work verified that CCR7 impacts the extent of primary pterygia invading the cornea and inflammation at the ocular surface, which may provide a possibility for a further in-depth understanding of the immunological mechanism in pterygia.

Impact of pterygium on central corneal thickness measured by optical coherence tomography in older adults.

PURPOSE: To measure the central corneal thickness (CCT) using anterior segment optical coherence tomography (AS-OCT) in older adults with and without pterygium from the Brazilian Amazon Region Eye Survey (BARES). METHODS: BARES is a population-based epidemiological cross-sectional study conducted in Parintins city. Participants were residents ≥45 years of age identified through a door-to-door interview. Eligible participants were invited for a comprehensive eye exam. Pterygium occurrence and severity were assessed by ophthalmologists through slit-lamp examination considering its location (nasal or/and temporal) and severity (lesion with extension <3 mm, ≥3 mm not reaching the pupillary margin or ≥3 mm reaching the pupillary margin). CCTs were obtained and measurements from the more severely affected eye were included. Images were analyzed offline by masked observers. RESULTS: A total of 671 subjects, 533 (79.4%) with pterygium in at least one eye and 138 (20.6%) without pterygium in either eye, were examined. The mean CCT evaluated by multiple linear regression and adjusted for demographic variables and pterygium severity was 521 ± 34 µm (median = 521; range = 304-665). Decreased CCT was significantly associated with age and pterygium severity. Individuals aged 65-74 years had CCT 7 µm thinner than those aged 45-54 years (p = 0.044), individuals aged 75 years and older had CCT 15 µm thinner than those aged 45-54 years (p = 0.001), and eyes with severe pterygium had CCT 33 µm thinner than eyes without pterygium (p < 0.001). CONCLUSIONS: The CCT analysis in this population-based sample shows that a thinner cornea is associated with pterygium severity and older age.

Impairment of autophagy promotes human conjunctival fibrosis and pterygium occurrence via enhancing the SQSTM1-NF-κB signaling pathway.

Pterygium is a common ocular disease with a high recurrence rate, characterized by hyperplasia of subconjunctival fibrovascular tissue. Autophagy, an important process to maintain cellular homeostasis, participates in the pathogenic fibrosis of different organs. However, the exact role of autophagy in pterygium pathogenesis remains unknown. Here, we found that autophagic activity was decreased in human pterygium tissues compared with adjacent normal conjunctival tissues. The in vitro model of fibrosis was successfully established using human primary conjunctival fibroblasts (ConFB) treated with transforming growth factor-ß1 (TGF-ß1), evidenced by increased fibrotic level and strong proliferative and invasive capabilities. The autophagic activity was suppressed during TGF-ß1- or ultraviolet-induced fibrosis of ConFB. Activating autophagy dramatically retarded the fibrotic progress of ConFB, while blocking autophagy exacerbated this process. Furthermore, SQSTM1, the main cargo receptor of selective autophagy, was found to significantly promote the fibrosis of ConFB through activating the PKCι-NF-κB signaling pathway. Knockdown of SQSTM1, PKCι, or p65 in ConFB delayed TGF-ß1-induced fibrosis. Overexpression of SQSTM1 drastically abrogated the inhibitory effect of rapamycin or serum starvation on TGF-ß1-induced fibrosis. Collectively, our data suggested that autophagy impairment of human ConFB facilitates fibrosis via activating the SQSTM1-PKCι-NF-κB signaling cascades. This work was contributory to elucidating the mechanism of autophagy underlying pterygium occurrence.

Anterior segment optical coherence tomography in ocular surface tumours and simulating lesions.

This study aims to systematically review the reported literature on the use of anterior segment optical coherence tomography (AS-OCT) in ocular surface tumours and simulating lesions. A systematic literature search was done using PubMed, Scopus, and Web of Science databases between January 2002 and December 2021. On AS-OCT, ocular surface squamous neoplasia typically demonstrate epithelial thickening, epithelial hyperreflectivity, and an abrupt transition between normal and abnormal epithelium. Conjunctival nevi usually show mildly hyperreflective epithelium of normal thickness, internal hyperreflectivity, and intralesional cysts which is the hallmark of this tumour. Primary acquired melanosis presents with normal thickness epithelium, basal epithelial hyperreflectivity, and absence of cysts. Conjunctival melanoma demonstrates hyperreflective normal/thickened epithelium, hyperreflective basal epithelium, internal hyperreflectivity, and absence of intralesional cysts. Conjunctival lymphoma shows homogenous, low-medium reflective subepithelial lesions with smooth borders, and dot-like infiltrates. Benign reactive lymphoid hyperplasia findings are similar to lymphoma but the infiltrates are more hyperreflective compared to lymphoma. Pterygium shows thickened conjunctival epithelium, epithelial hyperreflectivity, and subepithelial wedge-shaped hyperreflective tissue separated from the overlying epithelium by a cleavage plane. Pinguecula demonstrates mildly thickened epithelium and similar findings with pterygium but does not extend beyond the corneal limbus. This review shows that AS-OCT, as a noninvasive tool, has potential uses in the differential diagnosis of ocular surface tumours and simulating lesions. Major limitations of AS-OCT include limited visualization of the posterior border of thick, keratinized, and pigmented tumours and lack of assessment of large conjunctival tumours in a single cut.

Changes in TRPV1 Expression as Well as Substance P and Vasoactive Intestinal Peptide Levels Are Associated with Recurrence of Pterygium.

Pterygium, a disease of the ocular surface, is characterized by the proliferation and invasion of fibrovascular tissue. Chronic inflammation contributes to pterygium occurrence. Sensory neuropeptides of TRPV1-positive nerve fibers are involved in inflammation and corneal wound healing. The possible association between TRPV1 in nerve fibers and neuropeptides such as Substance P (SP) and Vasoactive Intestinal Peptide (VIP) in the recurrence of pterygium has not been examined before. The pterygia from 64 patients were used to determine changes in SP and VIP levels using 10 min acetic-acid extraction that yielded mainly neuronal peptides. There was a sufficient amount of pterygium tissues from the 35 patients for further immunohistochemical analysis of TRPV1 and S100, which is a glial marker to visualize nerve fibers. SP and VIP levels increased markedly in cases with primary and secondary recurrences, and there was a close correlation between SP and VIP levels. TRPV1 expression increased in the epithelium, while stromal expression decreased in recurrences. Nerve fibers were demonstrated mainly in the stroma, and serial sections confirmed the localization of TRPV1 with the nerve fibers. These results together with previous findings demonstrated that the increased epithelial expression of TRPV1 in recurrent pterygia might be involved in the pathogenesis, and the inhibition of epithelial TRPV1 activity may prevent recurrence.

Histopathology-based diagnosis of Mooren's ulcer concealed beneath the pterygium on eye.

Mooren's ulcer (MU) is a chronic and painful ulcerative keratitis that is difficult to diagnose, especially when concealed beneath the pterygium, which is a common, benign, wedge-shaped, fleshy tissue growth of the conjunctiva extending onto the cornea. The coexistence of MU and pterygium is extremely rare. A 41-year-old man presented with a 2-month history of unprovoked redness, pain, and blurred vision in the right eye. Corneal epithelial defects around the pterygium head were noted upon slit-lamp examination and fluorescein staining. The patient was initially misdiagnosed with a corneal epithelial defect and pterygium. The initial treatments with anti-inflammatory and corneal epithelial growth promotion tear agents failed. Anterior segment optical coherence tomography (AS-OCT) showed corneal stromal lysis thinning, and in vivo confocal microscopy (IVCM) revealed marked inflammatory cell infiltration and stromal degeneration. We suspected the pathology was an immune-related or tumor-related corneal ulcer. The MU concealed beneath the pterygium was diagnosed by histopathological examination of a biopsy specimen that presented typical localized loss of the corneal epithelium and Bowman's layer, stromal degeneration, and inflammatory cell infiltration. Finally, we performed lamellar keratoplasty (LKP) combined with pterygium excision surgery. The patient recovered with no complications or recurrence during the 1-year follow-up period. Few cases of MU concealed beneath the pterygium have been reported. It is beneficial to rule out the pathological changes concealed beneath the pterygium, combined with multiple means of examination such as slit-lamp examination, AS-OCT, and IVCM. A histopathological examination should be performed to establish a diagnosis.

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.

[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.

Case Report of Conjunctival Melanoacanthoma.

PURPOSE: The purpose of this study was to describe a case of conjunctival melanoacanthoma, an exceedingly rare condition that has yet to be fully described in the literature. METHODS: Melanoacanthomas are most commonly seen on the skin or oral mucosa and are believed to result from local irritation or trauma. A 34-year-old Hispanic man presented with a painless, solitary, pigmented conjunctival lesion, in addition to bilateral pterygia suggesting chronic solar damage. The lesion was excised and sent for analysis. RESULTS: Histopathologic analysis of tissue samples demonstrated melanocyte proliferation and epithelial dysplasia, yielding a final pathologic diagnosis of conjunctival melanoacanthoma with dysplastic and acantholytic-type features. The patient is being closely followed and has not had recurrence of the lesion. CONCLUSIONS: Only 1 prior case of conjunctival melanoacanthoma has been documented. As such, there is no standard of care regarding appropriate management.

Histopathological Rate of Ocular Surface Squamous Neoplasia in Clinically Suspected Pterygium Specimens: 10-Year Results.

PURPOSE: The aim of this study was to evaluate the prevalence of histopathologically confirmed ocular surface squamous neoplasia (OSSN) in clinically diagnosed pterygium samples at a tertiary center in Northern California, over a 10-year period (2009-2019). METHODS: A retrospective chart review of patients older than 18 years with clinically diagnosed benign pterygium requiring excision was conducted. Clinically suspected pterygia were excised using standard techniques and routinely submitted to the University of California Davis for pathologic evaluation. Demographic, clinical, surgical, and pathological information were recorded and analyzed. The prevalence rate of OSSN was calculated. RESULTS: A total of 348 consecutive specimens were evaluated. The mean (±SD) age of the patients was 58 ± 12 years, with a near equal sex representation. A total of 57 (16%) pterygia were recurrent at initial presentation. Histopathologic results demonstrated a single case of OSSN. This patient did not have a documented history of carcinoma in other organs or any history of herpes virus, human papilloma virus, or human immunodeficiency virus infection. CONCLUSIONS: The prevalence of histopathological OSSN in clinically suspected pterygia within our sample was approximately 0.3%. Because of shared clinical characteristics of pterygia and OSSN, a high index of suspicion and judicious use of anterior segment optical coherence tomography enable for effective preoperative diagnosis of OSSN. However, in the absence of clinical expertise or high-resolution optical coherence tomography, routine tissue pathologic examination may be warranted.

MiR-15a Participated in the Pathogenesis of Pterygium via Targeting BCL-2: An Experimental Research.

PURPOSE: To compare the expression levels of miR-15a between pterygium and normal conjunctiva, and further investigate the potential role of miR-15a in the progression of pterygium. METHODS: 21 cases of primary pterygium were enrolled in our study. The length of the pterygium invaded into the cornea and the total thickness of the pterygium were measured with anterior segment optical coherence tomography (AS-OCT). The pterygial and adjacent normal conjunctival samples of the 21 patients were collected. Expressions of miR-15a, BCL-2, Bax in both pterygium and normal conjunctiva were measured, and correlations between miR-15a and BCL-2, miR-15a and Bax, miR-15a and clinical parameters were made. Pterygium epithelial cells (PECs) were isolated, cultured and transfected with miR-15a mimic or miR-15a inhibitor to interfere the miR-15a expression levels. The regulation of BCL-2 expression by miR-15a was examined with Real-Time PCR (RT-PCR), Western blot and immunofluorescence. The regulation of Bax expression by miR-15a was also examined with Real-Time PCR (RT-PCR) and Western blot. The cell viability of the transfected PECs was measured with the CCK-8 assay and the apoptosis in these cells was detected using the TUNEL assay. RESULTS: The expression of miR-15a, Bax were significantly decreased while the BCL-2 was significantly increased in pterygium (p < .05). There was a negative correlation in expression between miR-15a and BCL-2 in pterygium tissues (r = -0.516, p < .05). We also found that relative miR-15a level was positively correlated with the length of pterygium invaded into the cornea (r = -0.570, p < .05). In cultured PECs, miR-15a could downregulate the expression of BCL-2 and upregulate the expression of Bax. Promotion of miR-15a could suppress cell proliferation and promote cell apoptosis in cultured PECs. CONCLUSIONS: Our study demonstrated that decreased expression of miR-15a in pterygium might be associated with the apoptosis and proliferation of abnormal cell via regulating BCL-2, which could subsequently contribute to the development of pterygium. Downregulation of miR-15a might also contribute to the pathogenesis of pterygium by other mechanisms including abnormal proliferation and neovascularization, which remain to be investigated.

Transcriptome Analysis of Pterygium and Pinguecula Reveals Evidence of Genomic Instability Associated with Chronic Inflammation.

Solar damage due to ultraviolet radiation (UVR) is implicated in the development of two proliferative lesions of the ocular surface: pterygium and pinguecula. Pterygium and pinguecula specimens were collected, along with adjacent healthy conjunctiva specimens. RNA was extracted and sequenced. Pairwise comparisons were made of differentially expressed genes (DEGs). Computational methods were used for analysis. Transcripts from 18,630 genes were identified. Comparison of two subgroups of pterygium specimens uncovered evidence of genomic instability associated with inflammation and the immune response; these changes were also observed in pinguecula, but to a lesser extent. Among the top DEGs were four genes encoding tumor suppressors that were downregulated in pterygium: C10orf90, RARRES1, DMBT1 and SCGB3A1; C10orf90 and RARRES1 were also downregulated in pinguecula. Ingenuity Pathway Analysis overwhelmingly linked DEGs to cancer for both lesions; however, both lesions are clearly still benign, as evidenced by the expression of other genes indicating their well-differentiated and non-invasive character. Pathways for epithelial cell proliferation were identified that distinguish the two lesions, as well as genes encoding specific pathway components. Upregulated DEGs common to both lesions, including KRT9 and TRPV3, provide a further insight into pathophysiology. Our findings suggest that pterygium and pinguecula, while benign lesions, are both on the pathological pathway towards neoplastic transformation.

SPARC knockdown attenuated TGF-ß1-induced fibrotic effects through Smad2/3 pathways in human pterygium fibroblasts.

PURPOSE: Secreted protein acidic and rich in cysteine (SPARC), a matricellular glycoprotein, has been found to regulate processes involved in fibrotic diseases. The aim of this study was to investigate the anti-fibrotic effects of SPARC in primary human pterygium fibroblasts (HPFs) and elucidate the underlying mechanisms. METHODS: The expression of SPARC in HPFs was knocked down by RNA interference-based approach. Subsequently, we examined the expression of profibrotic markers induced by transforming growth factor-ß1 (TGF-ß1), including type 1 collagen (COL1), α-smooth muscle actin (α-SMA), and fibronectin (FN). The changes in signaling pathways and matrix metalloproteinases (MMPs) were also detected by western blotting. The cellular migration ability, proliferation ability, apoptosis, and contractile phenotype were detected using the wound healing assay, Cell Counting Kit-8 assay, flow cytometry, and collagen gel contraction assay, respectively. The interaction between SPARC and TGF-ß RII was detected by Co-IP RESULTS: Silencing of SPARC inhibited the basal and TGF-ß1-induced expression of COL1, α-SMA, and FN in HPFs, and suppressed the expression of p-Smad2, p-Smad3, Smad4 and MMP2, MMP9. The downregulation of SPARC also attenuated the cell migration and contractile phenotype of HPFs. SPARC could bind to TGF-ßRII under TGF-ß1 treatment. However, knockdown of SPARC did not affect the proliferation and apoptosis of HPFs. CONCLUSION: SPARC knockdown attenuated the fibrotic effect induced by TGF-ß1 at least in part by inactivating the Smad2/3 pathways in HPFs. Therefore, SPARC may be a promising therapeutic target for the treatment of pterygium.

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-The Good, the Bad, and the Ugly.

Pterygium is a multifaceted pathology that displays apparent conflicting characteristics: benign (e.g., self-limiting and superficial), bad (e.g., proliferative and potentially recurrent) and ugly (e.g., signs of preneoplastic transformation). The natural successive question is: why are we lacking reports showing that pterygium lesions become life-threatening through metastasis, especially since pterygium has considerable similarities with UV-related malignancies on the molecular level? In this review, we consider how our pathophysiological understanding of the benign pterygium pathology overlaps with ocular surface squamous neoplasia and skin cancer. The three UV-related disorders share the same initial insult (i.e., UV radiation) and responsive repair mechanisms to the ensuing (in)direct DNA damage. Their downstream apoptotic regulators and other cellular adaptations are remarkably alike. However, a complicating factor in understanding the fine line between the self-limiting nature of pterygium and the malignant transformation in other UV-related diseases is the prominent ambiguity in the pathological evaluation of pterygium biopsies. Features of preneoplastic transformation (i.e., dysplasia) are used to define normal cellular reactions (i.e., atypia and metaplasia) and vice versa. A uniform grading system could help in unraveling the true nature of this ancient disease and potentially help in identifying the earliest intervention point possible regarding the cellular switch that drives a cell's fate towards cancer.

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.

The role of cyclin D1, BCL-2, p53 and Ki-67 in epithelial cells in the etiopathogenesis of pterygium.

CONTEXT: Pterygium is a degenerative disease that consists of conjunctival epithelia and fibrovascular tissue. Some studies suggest that there is a defect in the regulation of apoptosis in the epithelial cell cycle characterized by the development of the disease. But, still this matter being debated. AIMS: In this study, the clinical, histopathological data, and the expression of the cell cycle regulator Cyclin D1, anti-apoptotic BCL-2, tumor suppressor p53, and cell proliferation marker Ki-67 were searched in pterygium samples. SUBJECTS AND METHODS: The study enrolled 62 cases of primary pterygium who underwent excision between 2014 and 2017. Recurrent and pseudo-pterygium cases were excluded from series. The clinical data were obtained from the patient files and the slides were reevaluated for the histopathological data. Slides of all were stained by Cyclin D1, BCL-2, and Ki-67 by the immunohistochemical method. For each immunohistochemical marker, first the staining was determined as negative or positive. Then if there is a staining, the hot zone (the area containing more positive cells) was determined and staining percentage (SP) was assessed by counting positive cells/100 epithelial cells). RESULTS: Solar elastosis, edema, inflammation, and epithelial dysplasia were found statistically different between the control group and the patient group (P value <0.001, <0.001, <0.001 <0.001, respectively). A significant difference was found for staining percentage (SP) of Ki-67, p53, BCL-2 between the control group and the patient group (P values <0.001, 0.002, <0.001, respectively). There were no significant differences in the SP of Cyclin D1 between the two groups (p: 0,133). CONCLUSIONS: Our results indicate an abnormal expression of p53, BCL-2 and elevated proliferation measured by Ki-67 in pterygium samples when compared to normal conjunctiva. Besides the mesenchymal changes, the increased proliferation and the failure of apoptosis in the epithelial cells participate in the development of pterygium, as well.