*4.1.3.1 Conjunctival intraepithelial neoplasia (CIN)*

CIN (others prefer the terms mild, moderate, or severe dysplasia) appears as a fleshy, sessile or minimally elevated lesion usually arising at the limbus in the interpalpebral fissure and less commonly in the forniceal or palpebral conjunctiva A white plaque (leukoplakia) may be present.

Histopathologically, it is characterized by the presence of immature abnormal cells. The several types of displasia depend on the presence of these abnormal epithelial cells which may partially (mild dysplasia), nearly fully (moderate dysplasia) or fully replace (severe dysplasia) the normal cells. Carcinoma-in-situ represents full thickness replacement by abnormal epithelial cells.

### *4.1.3.2 OCT appearance*

Due to its epithelial onset, distinctive criteria of ASOCT are a thickened, hyper-reflective epithelial layer with an abrupt transition from normal to abnormal epithelium [23].

Shousha et al. [26] demonstrated that the use of UHR-OCT (ultra-high resolution OCT) in the diagnosis and follow-up of conjunctival and corneal intraepithelial neoplasia (CCIN) is possible.

In the different types of CIN the authors found thickened hyperreflective epithelium and abrupt transition from normal to hyperreflective epithelium. Their results demonstrated that macroscopically resolved residual tumor nodules can be visualized by UHR-OCT [26]. A disadvantage of UHR-OCT is that it is not high enough to assess intracellular characteristics.

## *4.1.4 Squamous cell carcinoma*

As above mentioned, the SCC develops when the abnormal cells have invaded the stroma. Histopathologically, invasive squamous cell carcinoma is characterized by malignant squamous cells that have violated the basement membrane and have grown in sheets or cords into the stromal tissue.

#### *4.1.4.1 OCT appearance*

In the OCT imaging a squamous cell carcinoma is recognizable since the epithelium appears hyperreflective and thickened [27]. Several reports demonstrated that the ASOCT may be useful in the differentiation between SCC and similar lesions like amelanotic melanoma and corneal fibrosis or from pterygia with a very good correlation with histopathology [23, 26, 27]. HR-OCT can also be used for the monitoring of the resolution of SCC during therapy. In this way, HR-OCT can detect subtle residual epithelial thickening which is not visible on clinical examination [20].

#### *4.1.5 Malignant melanoma*

A Conjunctival is characterized by a high clinical variability. It may be pigmented and tan or, more generally, elevated conjunctival lesion, located in possible several parts of conjunctiva.

Histopathologically, conjunctival melanoma is composed of variably pigmented malignant melanocytes within the conjunctival stroma. Patients are typically 60–70 years old and present with a nodular mass arising either de novo, from a nevus, or from PAM with atypia [25]. Often prominent feeder vessels and surrounding flat PAM are present. Melanoma-related death rates are 5–17% at 5 years and 9–35% at 10 years, depending on the precursor lesion. Non-limbal locations portend a poorer prognosis. De novo melanomas tend to have the worst prognosis. Local recurrence is common and it can be 45% at 5 years and 59% at 10 years [25].

#### *4.1.5.1 OCT appearance*

AS-OCT images show a hyperreflective subepithelial lesion. The epithelium is a normal to slightly thick layer of epithelium with variable hyperreflectivity of the basal epithelium, which suggests some involvement of the epithelium with atypical melanocytes [21].

#### *4.1.6 Conjunctival lymphoma*

Conjunctiva lymphoma may appear as a diffuse, slightly elevated pink mass, termed "salmon patch." The usual localization is at the fornix, usually hidden by the eyelid in the superior and inferior quadrants and not in the horizontal exposed parts of the bulbar conjunctiva or the limbus. Sometimes they arise from caruncle or plica semilunaris, but almost never in the palpebral conjunctiva.

The Oct appeareance: a recent published study [21] showed the AS-OCT appearance of the lesion, characterized by a normal layer of epithelium overlying homogeneous, dark, hyporeflective subepithelial lesions with smooth borders (**Figures 2** and **3**). The lesions can often contain monomorphic, stippled, dot-like infiltrates that correspond to the infiltration of monoclonal lymphocytes.

The author states that for both melanomas and lymphomas, ASOCT images do not always help the clinician obtain a definitive diagnosis as they do for OSSN, but can help guide the differential diagnosis. Nevertheless, the histopathologic analysis of tissue is needed for final confirmation.

**55**

**4.2 Conjunctival diseases**

In the pterygium the ASOCT can represent a useful tool if the corneal stromal

ASOCT images of pterygia demonstrate a thin or normal layer of epithelium with varying levels of hyperreflectivity overlying a dense, hyperreflective, fibrillary subepithelial lesion that is between the corneal epithelium and Bowman's

One of the aspects possibly involved in its recurrence is the pterygium length. Welch et al. studied the difference between the measurements of a pterygium using a slit-lamp or the ASOCT imaging. They demonstrated that ASOCT allows to accurately determine the extension of a pterygium on the cornea [28]. Moreover, ASOCT can help to distinguish pterygia from OSSN: various reports [18, 26–28] demonstrated statistically significant differences in epithelial thickness and location between these two lessons (thicker and epithelial for OSSN thinner and subepithelial for pterygia). Kieval et al. showed [27] that the average epithelial thickness in

invasion needs to be evaluated and also in the postoperative management.

*OCT image: note the hyporeflective lesion with smooth posterior border.*

*4.2.1 Pterygium*

**Figure 3.**

**Figure 2.**

layer [21].

*OCT Applications in Conjunctival Disease DOI: http://dx.doi.org/10.5772/intechopen.87162*

*Clinical appearance of conjunctival lymphoma.*

*OCT Applications in Conjunctival Disease DOI: http://dx.doi.org/10.5772/intechopen.87162*

*A Practical Guide to Clinical Application of OCT in Ophthalmology*

grown in sheets or cords into the stromal tissue.

*4.1.4.1 OCT appearance*

examination [20].

10 years [25].

*4.1.5.1 OCT appearance*

melanocytes [21].

*4.1.6 Conjunctival lymphoma*

*4.1.5 Malignant melanoma*

several parts of conjunctiva.

by malignant squamous cells that have violated the basement membrane and have

In the OCT imaging a squamous cell carcinoma is recognizable since the epithelium appears hyperreflective and thickened [27]. Several reports demonstrated that the ASOCT may be useful in the differentiation between SCC and similar lesions like amelanotic melanoma and corneal fibrosis or from pterygia with a very good correlation with histopathology [23, 26, 27]. HR-OCT can also be used for the monitoring of the resolution of SCC during therapy. In this way, HR-OCT can detect subtle residual epithelial thickening which is not visible on clinical

A Conjunctival is characterized by a high clinical variability. It may be pigmented and tan or, more generally, elevated conjunctival lesion, located in possible

Histopathologically, conjunctival melanoma is composed of variably pigmented malignant melanocytes within the conjunctival stroma. Patients are typically 60–70 years old and present with a nodular mass arising either de novo, from a nevus, or from PAM with atypia [25]. Often prominent feeder vessels and surrounding flat PAM are present. Melanoma-related death rates are 5–17% at 5 years and 9–35% at 10 years, depending on the precursor lesion. Non-limbal locations portend a poorer prognosis. De novo melanomas tend to have the worst prognosis. Local recurrence is common and it can be 45% at 5 years and 59% at

AS-OCT images show a hyperreflective subepithelial lesion. The epithelium is a normal to slightly thick layer of epithelium with variable hyperreflectivity of the basal epithelium, which suggests some involvement of the epithelium with atypical

Conjunctiva lymphoma may appear as a diffuse, slightly elevated pink mass, termed "salmon patch." The usual localization is at the fornix, usually hidden by the eyelid in the superior and inferior quadrants and not in the horizontal exposed parts of the bulbar conjunctiva or the limbus. Sometimes they arise from caruncle or plica

The Oct appeareance: a recent published study [21] showed the AS-OCT appearance of the lesion, characterized by a normal layer of epithelium overlying homogeneous, dark, hyporeflective subepithelial lesions with smooth borders (**Figures 2** and **3**). The lesions can often contain monomorphic, stippled, dot-like

The author states that for both melanomas and lymphomas, ASOCT images do not always help the clinician obtain a definitive diagnosis as they do for OSSN, but can help guide the differential diagnosis. Nevertheless, the histopathologic analysis

infiltrates that correspond to the infiltration of monoclonal lymphocytes.

semilunaris, but almost never in the palpebral conjunctiva.

of tissue is needed for final confirmation.

**54**

**Figure 2.** *Clinical appearance of conjunctival lymphoma.*

#### **Figure 3.**

*OCT image: note the hyporeflective lesion with smooth posterior border.*

## **4.2 Conjunctival diseases**

#### *4.2.1 Pterygium*

In the pterygium the ASOCT can represent a useful tool if the corneal stromal invasion needs to be evaluated and also in the postoperative management.

ASOCT images of pterygia demonstrate a thin or normal layer of epithelium with varying levels of hyperreflectivity overlying a dense, hyperreflective, fibrillary subepithelial lesion that is between the corneal epithelium and Bowman's layer [21].

One of the aspects possibly involved in its recurrence is the pterygium length. Welch et al. studied the difference between the measurements of a pterygium using a slit-lamp or the ASOCT imaging. They demonstrated that ASOCT allows to accurately determine the extension of a pterygium on the cornea [28]. Moreover, ASOCT can help to distinguish pterygia from OSSN: various reports [18, 26–28] demonstrated statistically significant differences in epithelial thickness and location between these two lessons (thicker and epithelial for OSSN thinner and subepithelial for pterygia). Kieval et al. showed [27] that the average epithelial thickness in

#### *A Practical Guide to Clinical Application of OCT in Ophthalmology*

the 17 epithelial squamous cell carcinomas (SCC) was 346 μm, compared to 101 μm in the 17 pterygia. Using a cut-off value of 142 μm results in a sensitivity of 94% and a specificity of 100% in differentiating SCC from pterygia.

However, this imaging technique was less useful in evaluating pigmented lesions [20].

#### *4.2.2 Graft-versus-host disease (GVHD)*

Graft-versus-host disease (GVHD) is a major complication following allogeneic hematopoietic. It usually involves several organs, and the ocular involvement occurs in ~60% of GVHD patients [1, 3, 4], particularly affecting cornea, conjunctiva, lids and lacrimal gland, resulting in a wide spectrum of ocular complications [29–31] (**Figure4**).

A report of Peng Li et al. [32] investigates the role of the device in GVHD with a surprising result: the conjunctival image of GVHD shows a characteristic imaging with a much higher OCT signal on the surface in GVHD patients compared to those in normal subjects (**Figure 5**), most likely due to the conjunctival keratinization and to the conjunctival lymphatic vessels dilated.

#### *4.2.3 Ocular cicatricial pemphigoid*

Mucous membrane pemphigoid (MMP) is an autoimmune, sub-epithelial blistering, potentially blinding disease characterized by scarring and shrinkage of mucosal membranes, including the conjunctival mucosa, oral cavity, esophagus, trachea and genitals [34]. When clinical signs are detected firstly in the conjunctiva, the disease is named "ocular cicatricial pemphigoid" (OCP) [33, 34] (**Figure 6**).

The diagnosis of ocular cicatricial pemphigoid (OCP) is challenging, especially when the pathology is in its early stages, due to the OCP a specific ocular signs which are not easy to recognize through slit lamp examination [35].

The ethiopathogenic mechanism by which the OCP produces its typical conjunctival lesions is a subepithelial inflammation mediated by autoimmunity against a multiplicities of possible antigens located in membrane basement of the deeper layers of the conjunctiva: this process leads t to a subconjunctival fibrosis and cicatricial conjunctivitis. Therefore, the ASOCT could potentially be a useful device to detect and study initial modifications of the conjunctival areas where OCP starts its damages, possibly when it is not recognizable by using the slit lamp alone. In our cohort of patients (unpublished data), we noticed in a great percentage some abnormalities in the OCT image: (**Figure 7**) a diffuse increase of optical reflectivity

#### **Figure 4.**

*Image of conjunctiva from a patient suffering from GVHD: a symblephara with the surrounding subepithelial fibrosis.*

**57**

located in the sub-epithelial conjunctival space and the presence of some folds located at different depths in the conjunctival substantia propria thickness, appearing in different shapes. These signs are usually located in the subepithelial space

(distance 25 ± 8 μm from epithelium).

*OCT appearance of the patient in Figure 6.*

None of the authors have conflict of interest.

**Conflict of interest**

*OCT Applications in Conjunctival Disease DOI: http://dx.doi.org/10.5772/intechopen.87162*

*OCT appearance of GVHD: diffuse hyperreflectivity of both epithelial and stromal area.*

*Ocular cicatricial pemphigoid: note the fornix foreshortening and symblephara.*

**Figure 5.**

**Figure 6.**

**Figure 7.**

*OCT Applications in Conjunctival Disease DOI: http://dx.doi.org/10.5772/intechopen.87162*

**Figure 5.**

*A Practical Guide to Clinical Application of OCT in Ophthalmology*

a specificity of 100% in differentiating SCC from pterygia.

*4.2.2 Graft-versus-host disease (GVHD)*

to the conjunctival lymphatic vessels dilated.

*4.2.3 Ocular cicatricial pemphigoid*

lesions [20].

the 17 epithelial squamous cell carcinomas (SCC) was 346 μm, compared to 101 μm in the 17 pterygia. Using a cut-off value of 142 μm results in a sensitivity of 94% and

However, this imaging technique was less useful in evaluating pigmented

Graft-versus-host disease (GVHD) is a major complication following allogeneic hematopoietic. It usually involves several organs, and the ocular involvement occurs in ~60% of GVHD patients [1, 3, 4], particularly affecting cornea, conjunctiva, lids and lacrimal gland, resulting in a wide spectrum of ocular complications [29–31] (**Figure4**). A report of Peng Li et al. [32] investigates the role of the device in GVHD with a surprising result: the conjunctival image of GVHD shows a characteristic imaging with a much higher OCT signal on the surface in GVHD patients compared to those in normal subjects (**Figure 5**), most likely due to the conjunctival keratinization and

Mucous membrane pemphigoid (MMP) is an autoimmune, sub-epithelial blistering, potentially blinding disease characterized by scarring and shrinkage of mucosal membranes, including the conjunctival mucosa, oral cavity, esophagus, trachea and genitals [34]. When clinical signs are detected firstly in the conjunctiva, the disease is named "ocular cicatricial pemphigoid" (OCP) [33, 34] (**Figure 6**). The diagnosis of ocular cicatricial pemphigoid (OCP) is challenging, especially

when the pathology is in its early stages, due to the OCP a specific ocular signs

The ethiopathogenic mechanism by which the OCP produces its typical conjunctival lesions is a subepithelial inflammation mediated by autoimmunity against a multiplicities of possible antigens located in membrane basement of the deeper layers of the conjunctiva: this process leads t to a subconjunctival fibrosis and cicatricial conjunctivitis. Therefore, the ASOCT could potentially be a useful device to detect and study initial modifications of the conjunctival areas where OCP starts its damages, possibly when it is not recognizable by using the slit lamp alone. In our cohort of patients (unpublished data), we noticed in a great percentage some abnormalities in the OCT image: (**Figure 7**) a diffuse increase of optical reflectivity

*Image of conjunctiva from a patient suffering from GVHD: a symblephara with the surrounding subepithelial* 

which are not easy to recognize through slit lamp examination [35].

**56**

**Figure 4.**

*fibrosis.*

*OCT appearance of GVHD: diffuse hyperreflectivity of both epithelial and stromal area.*

**Figure 6.** *Ocular cicatricial pemphigoid: note the fornix foreshortening and symblephara.*

**Figure 7.** *OCT appearance of the patient in Figure 6.*

located in the sub-epithelial conjunctival space and the presence of some folds located at different depths in the conjunctival substantia propria thickness, appearing in different shapes. These signs are usually located in the subepithelial space (distance 25 ± 8 μm from epithelium).
