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Year : 2017  |  Volume : 30  |  Issue : 2  |  Page : 466-474

Management of conjunctival lesions

Department of Ophthalmology, Faculty of Medicine, Menoufia University, Menoufia, Egypt

Date of Submission08-Sep-2015
Date of Acceptance02-Nov-2015
Date of Web Publication25-Sep-2017

Correspondence Address:
Manar F Dawoud
Department of Ophthalmology, Faculty of Medicine, Menofia University, Shebin El-Kom, Menoufia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1110-2098.215449

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The aim of this study was todetect, diagnose, and treat the different conjunctival lesions over a period of 1year.
The conjunctiva is the site of expression of many lesions either benign or malignant and are worthy of study.
Patients and methods
The study was conducted on patients attending the Outpatient Clinic of Ophthalmology in Menoufia University Hospital. It was conducted on 159patients with conjunctival lesions. Cases were examined and managed and the data were analyzed.
The study included 159cases. Overall, 100cases(62.9%) were male and 59cases(37.1%) were female. As regards age, 129cases(81%) were adult(mean age: 56±19.5) and30cases(19%) were children(mean age 11±6.5). Benign conjunctival lesions were the most common and represented 155cases(97.5%). The most common lesions were benign pigmented conjunctival lesions(41cases, 25.8%). The second most frequent lesions were pterygia(40cases, 25.2%). Pingueculae were the third most common conjunctival lesions(30cases, 18.9%). The remaining lesions included allergic conjunctival masses(16cases, 10%), epibulbar choriostomas(12cases, 7.6%), pyogenic granuloma(eight cases, 5%), orbital fat herniation(four cases, 2.5%), cystic lesions(four cases, 2.5%), and ocular surface squamous neoplasia(four cases, 2.5%). Conjunctival lesions among children(in the decreasing order of frequency) included conjunctival choriostomas(12cases, 30%), conjunctival nevi(11cases, 27.5%), allergic conjunctival lesions(eight cases, 20%), congenital melanosis(six cases, 15%), conjunctival Tenon's cyst(two cases, 5%), and one case of pyogenic granuloma(2.5%).
Benign conjunctival lesions are the most frequent, although some tumors may hide systemic association or malignant tumor. Hence, any suspicious conjunctival lesion should be excised carefully and sent for histopathological analysis and close follow-up is recommended.

Keywords: conjunctiva, nevus, ocular surface squamous neoplasia, pterygium

How to cite this article:
Sarhan ARE, Rajab GZ, Dawoud MF. Management of conjunctival lesions. Menoufia Med J 2017;30:466-74

How to cite this URL:
Sarhan ARE, Rajab GZ, Dawoud MF. Management of conjunctival lesions. Menoufia Med J [serial online] 2017 [cited 2020 Mar 30];30:466-74. Available from: http://www.mmj.eg.net/text.asp?2017/30/2/466/215449

  Introduction Top

The conjunctiva is a continuous mucous membrane that covers the anterior portion of the globe and is considered the site of manifestation of both local and systemic disease. Localized lesions often need surgical excision, and systemic conditions with local involvement of the conjunctiva are occasionally clinically thought to be tumors that require biopsy or excision. Clinical presentations and histopathological descriptions of various conjunctival conditions have been well documented, and surveys of the prevalence of epibulbar lesions without specification of age, in all age groups and in children, have been conducted[1],[2],[3],[4].

Excised lesions of the conjunctiva include a wide spectrum of conditions ranging from benign lesions, such as pterygium, solid dermoid, nevus, papilloma, hemangioma, and pyogenic granuloma, to precancerous ocular surface squamous neoplasia(OSSN) and aggressive malignancies, such as malignant melanoma, squamous cell carcinoma(SCC), or Kaposi's sarcoma. The differentiation of these lesions is based on the patient's history as well as clinical and histopathological features of the lesion[5].

Depending on the presumptive diagnosis and the size and extent of the lesion, management of a conjunctival lesion can consist of serial observation, incisional biopsy, excisional biopsy, cryotherapy, chemotherapy, radiotherapy, modified enucleation, orbital exenteration, or various combinations of these methods[6],[7].

The aim of the present work was to detect, diagnose, and treat the different conjunctival lesions over a period of 1year.

  Patients and Methods Top

A cross-sectional descriptive study was carried out on patients attending the Outpatient Clinic of Ophthalmology in Menoufia University Hospital during the period of study from April 2014 to April 2015. It was conducted on 159patients with symptomatizing or nonsymptomatizing conjunctival lesions. Before initiating this study, informed consent was obtained from patients and approval was obtained from the Ethics Committee of the Menoufia University Hospital. Full preoperative assessment of cases was carried out, including full ocular history, present history, past history, and family history, and full ocular and general examination.

Different lesions were managed as follows:

  • Pterygium: Surgical excision if indicated [conjunctival autograft, amniotic membrane graft (AMG), or intraoperative or preoperative mitomycin C(MM-C)]
  • Pinguecula: Topical steroid eye drops in acute pingueculitis
  • Nevus: Reassurance of the patient and follow-up/surgical excision and histopathology if there is cosmetic complaint or the nevus is suspicious
  • Dermoid and dermolipoma: Follow-up and observation/surgical debulking in large conjunctival dermoid with lagophthalmos and exposure keratopathy, or for cosmetic reasons after computed tomography(CT) scan and exclusion of Goldenhar syndrome
  • Orbital fat herniation: CT scan and follow-up/topical steroid and tear substitute eye drops in ocular surface irritation
  • Conjunctival retention cyst: Aspiration or surgical excision if large cyst
  • Pyogenic granuloma: Topical steroid eye drops and surgical excision if no improvement
  • OSSN: Excision with safety margin(double freeze thaw cryotherapy), histopathological examination, and postoperative topical MM-C if indicated.

  Results Top

The study included 159cases with conjunctival lesions; 100cases(62.9%) were male and 59cases(37.1%) were female. As regards the age, 129cases(81%) were noticed in adults and elderly, whereas 30cases(19%) were noticed in children. Benign conjunctival lesions were the most common and represented 155cases(97.5%) [Figure1]. The most frequently encountered lesions were benign pigmented conjunctival lesions(41cases, 25.8%). The second most frequently observed conjunctival lesions were pterygia, which represented 25.2%(40cases). Pingueculae were the third most common conjunctival lesions(30cases, 18.9%). The remaining lesions included allergic conjunctival masses and represented 10% of cases(16cases), epibulbar choriostomas that represented 7.6% of cases(12cases), and pyogenic granuloma that represented 5%(eight cases) of cases. Orbital fat herniation was observed in four cases(2.5%), cystic lesions represented 2.5%(four cases), and malignant OSSN 2.5% of cases(four cases). Conjunctival lesions among children(in the decreasing order of frequency) included conjunctival choriostomas (12cases, 30%), conjunctival nevi(11cases, 27.5%), allergic conjunctival lesions (eight cases, 20%), congenital melanosis (six cases, 15%), conjunctival Tenon's cyst (two cases, 5%), and one case of pyogenic granuloma (2.5%) [Table 1].
Figure 1: Distribution of conjunctival lesions in the study. OSSN, ocular surface squamous neoplasia.

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Figure 2: Large upper bulbar conjunctival nevus in a 14-year-old male patient with foreign body sensation since birth: (a) preoperatively, (b) immediately postoperatively, (c) 1 week later. (conjunctival epithelial defect), and. (d) 1 month postoperatively.

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Table 1: Distribution of excised conjunctival lesions in relation to the age and sex

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Benign pigmented conjunctival lesions

Benign pigmented conjunctival lesions were the most common and included 41cases(25.8%) of all cases in the study. Of those, 20cases(49%) were of conjunctival nevi, 10cases(24%) were of primary acquired melanosis(PAM), seven cases(17%) were of congenital melanosis, and four cases(10%) were of nevus of Ota [Figure1].

The mean age of presentation of cases with conjunctival nevi was 16years. Conjunctival nevi occurred most commonly on the bulbar conjunctiva(15cases), followed by the limbus(three cases), the fornix, and the caruncle(one case each). Four of them were accompanied with cystic spaces. Five were amelanotic and 15 were melanocytic nevi. Nevus excision was decided in 14cases mostly due to rapid growth and/or cosmetic purposes.

Primary acquired melanosis was observed in 10cases that were unilateral in fair-skinned people and appeared during adulthood, whereas congenital melanosis was observed in seven cases and was bilateral in dark-skinned people and dated since birth.


There were 40cases of [Figure3] pterygia with a percentage of 25.2%. Of those, 28cases were noticed in male patients and 12cases were noticed in female patients; 28cases were primary and 12cases were recurrent. The average age of patients with pterygium was 56years. In all, 11cases were bilateral and 29 were unilateral. Five cases showed nasal and temporal pterygium in the same eye. Overall, 90% of cases had occupation related to outdoor and sun exposure. Eight cases were observed because there was no indication for medical or surgical intervention; all were primary pterygia. Of the total cases, 10cases were managed with medical treatment to control recurrent inflammation. Surgery was the final line for treating them, and selection of the surgical technique was based on the surgeon's preference. In all, 22cases were managed surgically from the start. The number of cases that were managed surgically was 32; 20cases were primary and managed with excision with intraoperative MM-C application in seven cases, excision with conjunctival autograft in nine cases, and excision with limbal stem cell transplantation in four cases. Recurrent pterygia was noticed in 12cases and managed by means of excision with AMG of the resulting defect in three cases, preoperative subconjunctival injection of MM-C 1month before excision followed by excision and AMG in six cases, and conjunctival autograft in three cases.
Figure 3: Right primary nasal and temporal pterygium in a 65-year-old female patient. (a) Preoperative appearance and. (b) postoperative appearance after excision and AMG.

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Postoperative complications included the following:

  • Recurrence of the pterygium: It occurred in five previously recurrent cases [Figure4] and in four primary cases, with a total percentage of recurrence of 22.5%. It was noticed more with the bare sclera technique, followed by AMG and conjunctival autograft, and the least recurrence was noticed with MM-C application
  • Pyogenic granuloma was seen in three cases
  • Symblepharon in four cases
  • Loose graft stitches in three cases.
Figure 4: Postoperative complications of pterygium surgery. (a) Recurrent pterygium with lower symblepharon and (b) pyogenic granuloma.

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Figure 5: Limbal spring catarrh. (a and b) Before medical treatment and (c) after medical treatment.

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Pingueculae were observed in 30cases(18.9%). The mean age was 66years, and 19cases were noticed in male patients. 24cases were bilateral and six cases were unilateral. Overall, 17cases presented with ocular surface irritation symptoms and received topical medical treatment, and 13 were detected accidentally during routine ocular examination.

Allergic conjunctival masses

Allergic conjunctival masses were taken in concern as they were masquerading many lesions included in the study. They represented 10% of cases(16cases); 10cases were seen in male patients and the mean age of patients was 10years.

They included 10cases of limbal spring catarrh that was treated with topical steroid and antiallergic eye drops and six cases of phlycten that were associated with systemic parasitic infestation in five cases and with tuberculosis in one case.

Epibulbar choriostomas

Epibulbar choriostomas represented 7.6% of cases (12cases) [Figure6]. Seven cases were seen in male patients, and the mean age of the patients was 7years. Clinically and histopathologically, 50%(six cases) of cases were dermoid and the other 50%(six cases) were dermolipoma. Two dermolipoma cases were managed with CT scan of the orbit to exclude any orbital extension, followed by surgical debulking, and two limbal dermoid cases were managed with shaving, whereas the remaining dermoid and dermolipoma cases were only observed.
Figure 6: Bilateral superotemporal dermolipoma in an 8-year-old boy with Goldenhar syndrome. (a) Preoperative appearance and (b) postoperative appearance after debulking and amniotic membrane graft of the dermoid of the right side.

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Orbital fat herniation

Orbital fat herniation was noticed in 2.5% of cases(four cases), three male patients and one female patient, with a mean age of 44years. No specific recommendations, except CT of the orbit and follow-up, were given to the patient.

Pyogenic granuloma

Pyogenic granuloma represented 5% of cases(eight cases). All were unilateral; six cases were observed in male patients and the mean age was 18years [Figure7]. Five cases occurred after pterygium excision on the bulbar conjunctiva(four completely disappeared after medical treatment and one was removed surgically with cataract extraction). One case was observed after scleral buckle and pars plana vitrectomy with silicon oil injection operation and removed surgically with silicone oil removal. The remaining two cases appeared on the palpebral conjunctiva; one occurred after anterior lamellar separation for the treatment of upper eyelid entropion and regressed with medical treatment, and the other was overlying lower eyelid chalazion and was excised surgically.
Figure 7: Left bulbar pyogenic granuloma in a 40-year-old male patient following pterygium excision. (a) Before treatment and (b) 1 week after topical steroids eye drops.

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Conjunctival retention cysts

Conjunctival retention cysts constituted 2.5% of all cases and included four cases [Figure8]. Two cases were seen in male patients and the mean age was 24years. Two cases were large conjunctival retention cyst in adult male patients with a mean age of 29years and were managed with surgical excision and primary closure. Two cases of Tenon cyst complicating squint surgery were removed surgically.
Figure 8: Left large upper palpebral conjunctival cyst in a 42-year-old male. (a) Preoperatively and (b and c) postoperatively.

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Ocular surface squamous neoplasia

OSSN was seen in four cases(2.5%) [Figure9]. Tumors developed exclusively in male patients with past history of cigarette smoking and chronic sun exposure with a mean age of 64years. Histologic examination revealed that three cases were of conjunctival intraepithelial neoplasia(CIN) and one case was of SSC. All tumors involved the nasal bulbar conjunctiva and one wasencroaching on the cornea [Table1] and [Figure1],[Figure2],[Figure3],[Figure4],[Figure5],[Figure6],[Figure7],[Figure8],[Figure9],[Figure10],[Figure11].
Figure 9: Conjunctival rapidly growing gelatinous mass with surface mamillations in a 70-year-old male patient, exsmoker. (a) Preoperatively, (b) postoperatively, and (c) histopathology revealing carcinoma in situ without basement membrane invasion.

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Figure 10: Phlycten in an 11-year-old boy with Entamoeba histolytica cyst in stool analysis.

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Figure 11: Nevus of Ota.

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  Discussion Top

Cases of conjunctival lesions were selected, studied, and managed in this study. Management was either medical, surgical, or both, and many lesions were only observed with no definite treatment.

Our study was conducted on 159cases with conjunctival lesions; 100cases(62.9%) were male and 59cases(37.1%) were female. As regards the age, 129cases(81%) were adults(mean age: 56±19.5), whereas 30cases(19%) were children(mean age 11±6.5). However, the study conducted by Elshazly comprised 192 conjunctival specimens; 106(55.2%) obtained from male patients and 86(44.8%) from female patients and the mean age was 27.07±17years.

In our study, benign conjunctival lesions were the most common and represented 155cases(97.5%) and this is in agreement with many results such as those of Elshazly and colleagues, whostated that benign conjunctival lesions were the most frequent histologically diagnosed conjunctival lesions. The true malignant lesions were lower than that described in many reports[8],[9].

The most common benign lesions encountered in our study(in the decreasing order of frequency) were as follows: pigmented conjunctival lesions(nevus, PAM, congenital melanosis, and nevus of Ota), pterygia, and pingueculae. However, in the study by Grossnikiaus and colleagues the decreasing order of frequency was as follows: pterygium, nevus, dysplasia, nonspecific nongranulomatous inflammation, and epithelial inclusion cyst. Elshazly arranged them as follows; pyogenic granuloma, pigmented epithelial tumors, and cystic conjunctival lesions[9].

As regards conjunctival lesion prevalence in children, in our study, conjunctival choriostomas(30%), conjunctival nevi(27.5%), and allergic conjunctival lesions(20%) were the most frequent lesions. In a study on childhood epibulbar tumors, choriostomatous tumors, nevus, epithelial inclusion cyst, and papilloma pyogenic granuloma were the most common conjunctival tumors in order, as studied by Frederick etal.[10].

Pigmented conjunctival lesions

In our study, pigmented conjunctival lesions were the most common lesions reported in our study and represented 25.8% of all cases, but a clinical survey of 1643 melanocytic and nonmelanocytic conjunctival tumors conducted by Shields etal. [11] demonstrated that conjunctival tumors were of melanocytic origin in 53% of cases.

All pigmented lesions encountered in the present study were melanocytic in origin and they all were benign, and conjunctival nevi were the most common(49%). This is in favor with the results of Shields and colleagues[11],[12].

Concerning conjunctival nevi, the mean age in the study was 11years, whereas in the study conducted by Levecq and colleagues it was 5.3years. They occurred most commonly on the bulbar conjunctiva(75% of cases), followed by the limbus(15% of cases), the fornix, and the caruncle(5% of cases for each site). Four of them were accompanied with cystic spaces. Five were amelanotic and 15 were melanocytic nevi, whereas in the study conducted by Shields and colleagues, the nevus was brown in 65% and nonpigmented in 16%. The anatomical location of the nevus was on the bulbar conjunctiva in 72% of cases, the caruncle in 15% of cases, the plica semilunaris in 11%, the fornix in 1%, tarsus in 1%, and the cornea in less than 1% of all cases. Additional features included intralesional cysts(65%)[13],[14].

Nevus excision was decided in 70% of nevus cases in our study, mostly due to rapid growth and/or cosmetic purposes. However, Levecq etal. [13] excised 29% of conjunctival nevi for suspicion of malignancy, cosmetic purposes, and ocular surface irritation.

The other pigmented lesions seen in our study in decreasing order of incidence were as follows: PAM(24% of cases), congenital melanosis(17% of cases), and nevus of Ota(10% of cases). No cases of melanoma were seen, mostly due to the short period of the study, whereas Shields etal. [11] reported conjunctival melanoma in 25% of cases and PAM in 21% of cases.


As regards pterygium cases, the age of the patients included in this study ranged from 39 to 73years, with a mean age of 56years. This may be due to maximum exposure to sunlight and various irritants in this age, as pterygium is one of the sun-related conditions. This finding is in agreement with that recorded by some previous studies. Hilgers observed an increased tendency of development of pterygium among individuals in the age group40–49years. Moreover, Youngson found that the age of patients with pterygium ranged from 14 to 86years[15],[16].

In this study, it was noted that the incidence of pterygia was higher in male(70% of cases) than in female patients(30% of cases). This result is parallel to that found in the study by Saif and colleagues, who recorded 76.5% incidence in male patients. However, no sex difference was recorded by Hilgers and colleagues[15],[16],[17],[18].

As regards occupation, 90% of the cases in our study had an outdoor occupation with sun exposure. Dollezalova and colleagues noted that there was a statistically significant association between both ultraviolet rays exposure and pterygium formation. Cameron stated that primary pterygia but not the recurrent is thought to be produced by photobiological effects of ultraviolet light. Youngson noted that there was no obvious correlation between occupation and the incidence of pterygium[16],[18],[19],[20].

Different techniques have been adopted for pterygium excision with intention to prevent or reduce the recurrence rate. In this study, pterygia were managed surgically with excision using the bare sclera technique and intraoperative topical MM-C, preoperative injection of topical MM-C followed by simple excision one month later, excision with conjunctival autograft with or without limbal stem cell transplantation, or excision followed by AMG.

Pery etal. [21] stated that intraoperative administration of a single dose of 0.02% MM-C is an effective treatment for prevention of recurrence of pterygium and this is matched with the study results.

Chen etal. [22] reported that conjunctival autograft is effective as an adjunctive treatment after excision of primary pterygia in young, southern California, predominantly Hispanic population and has significantly lower rates of recurrence compared with bare sclera excision alone.

In our study, postoperative complications included the following: recurrence of the pterygium in 22.5% of all pterygium cases, pyogenic granuloma in three cases, symblepharon in four cases, and loose graft stitches in three cases. Luanratanakorn etal. [23] said that AMG had a higher recurrence rate compared with conjunctival autograft, and this is in agreement with our results.

Adams and colleagues have studied the different techniques for pterygium excision in their study and reported a recurrence rate of 39% in free conjunctival autograft technique and 9.4% in excision with AMG technique. Development of Tenon's granuloma, conjunctival cyst, and wound dehiscence were the complications reported by Bruce and colleagues[24],[25].

Pyogenic granuloma

Concerning pyogenic granuloma, eight cases were documented in this study(5% of cases), and seven of them following surgical trauma, mostly pterygium excision surgery. Onuigbo and Magulikestudied 21cases of pyogenic granuloma, all being unilateral. The male: female ratio was 3:1. The incidence was higher in male patients between 31 and 40 range, whereas the few female patients showed a wide age range. Most patients presented within 6months of noticing their lesions, which usually measured up to 1cm across. Trauma was documented in some cases. In our study, all cases were unilateral and the male-to-female ratio was 4:1[26].

Gabriela and colleagues stated that treatment with topical steroids is an effective initial treatment for most patients with pyogenic granulomas. Surgical excision is effective in patients who do not improve with topical medication, and this is in agreement with our study [27].

Ocular surface squamous neoplasia

In the present study, evidence of malignancy was proved in four cases(2.5%) and all were originating from stratified squamous epithelium and no other malignant tumors were seen mostly due to the short period of the study. These results are in agreement with the final results of Grossnikiaus and colleagues as the most common malignancies excised were SSC, melanoma, and pagetoid change associated with sebaceous cell carcinoma. SSC, arising from progressive stages of epithelial dysplasia, is the most common adult conjunctival malignancy. Melanoma is the second most common, and arises de novo, from nevi, or from progressive stages of acquired melanosis[9].

In our study, the four recorded cases occurred exclusively in male patients, with a mean age of 64years. Lee and Hirst reported that OSSN occurs mainly in male patients(78.5%) with a mean age of 60.1years(20–88years). Kim and colleagues stated that the mean age of patients was 64.8years(39–82years), suggesting that epithelial tumor developed in adults, and there was a male predominance. This was documented by Othman and colleagues as well[28],[29],[30],[31],[32].

Templeton and colleagues have suggested heavy cigarette smoking, ultraviolet light, and history of skin cancer as risk factors for OSSN, and this is in agreement with our study. Three of the four cases in the study were situated on the nasal bulbar conjunctiva and one of them was encroaching on the cornea. Kim and colleagues said that 87.8% of cases were located at the limbus[29],[33],[34],[35].

In the study by Kim and colleagues, the majority of OSSN were treated by means of simple excision(87.5%), after which there was a high rate of recurrence(23.3%). The main predictors for recurrence include histological grade of the lesion, corneal location, and larger size(>2mm)[29]. In the study by Peksayar and colleagues, which was conducted on a total of 55 participants(57 eyes), there were 19female and 36male patients and their ages ranged between 15 and 82years(mean: 55years). All eyes were treated with excision and cryosurgery with nitrous oxide probe. However, in our study, all cases were treated with excision with safety margin, absolute alcohol, and cryosurgery, and no recurrence was noted mostly due to small number of cases and short follow-up period[36].

Histopathologically, CIN was more common(75%) compared with invasive SCC. This is contradictory to the findings of Kim etal.[29], as in their study histological diagnosis was CIN in 26(46%) and invasive SCC of the conjunctiva in 31 eyes(54%).

Conjunctival choriostomas

Our study included 7.6% of cases of conjunctival choriostomas, whereas the study by Shields etal. [11] included 2% of conjunctival choriostomas.

Overall, 50% were dermolipoma and the other 50% were solid dermoid. Elshazly [8] documented 11cases of conjunctival choriostomas that included eight cases of dermolipoma(70%) and three cases of solid dermoid(30%).

In our study, four cases were managed surgically to improve cosmesis. Mansour etal. [37] stated that surgery may be indicated to improve vision or cosmesis, or to impede growth.

CT scan, excision, and histopathological studies were performed in most the cases of conjunctival dermoids in our study to differentiate them from other lesions. Colombo etal. [38] demonstrated that conjunctival dermoids and cysts of the orbit display clinical, radiological, and histopathological features that differentiate them from the more common dermoid cysts.

  Conclusion Top

Conjunctiva is the site of expression of the different conjunctival lesions, and benign conjunctival lesions are the most frequent, although some tumors may hide systemic association or malignant tumor. Hence, any suspicious conjunctival lesion should be excised carefully and sent for histopathological analysis, and close follow-up is recommended. However, it is recommended not to rush for excision of any conjunctival lesion, especially if it is not suspicious, as some lesions may be improved with medical treatment or require no treatment. In any conjunctival condition related to chronic sun exposure, preventative measures must remain the key to disease control.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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  [Figure1], [Figure2], [Figure3], [Figure4], [Figure5], [Figure6], [Figure7], [Figure8], [Figure9], [Figure10], [Figure11]

  [Table 1]


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