**2. Salzmann's nodular degeneration**

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

*(A) AS slit-lamp evaluation shows a corneal Dellen due to a previous pterygium surgery in the peripheral nasal area. (A, B) AS-OCT analysis demonstrating a thinning area in corneal periphery, allowing direct comparison between scans. (B) An evaluation from November 2013 and (C) an evaluation from January 2016. Even though there are some minimal changes in the thinning morphology, the length is almost equal, and the* 

*(A) AS slit-lamp biomicroscopy demonstrates a central and deep corneal opacification due to a traumatic perforation in a child. (B) AS-OCT evaluation shows a strange foreign body in the corneal endothelium (red arrow). The iris is incarcerated in the posterior corneal layers because of the perforating traumatism (blue arrow). (C) AS-OCT imaging displays an irregular stroma with hyper-reflective zones in the fibrosis areas. (D) The caliper tool can measure the respective corneal areas helping the physician to achieve a correct* 

(**Figures 5** and **6**) and measure the corneal scar depth before choosing a surgical procedure [12]. A noninvasive surgical technique, such as lamellar keratoplasty (LK) or phototherapeutic keratectomy (PTK), can be chosen when only the anterior corneal layers have been affected, while in other cases, penetrating keratoplasty (PKP) will be the unique option to restore the normal corneal structure. Corneal AS-OCT device also

Corneal AS-OCT device allows direct measurements and comparison with prior scans (**Figure 7**). The device is essential to evaluate cases with high risk of corneal

Degeneration can be defined as a gradual disruption of the normal condition of a tissue with a subsequent loss of functionality [14]. Corneal degeneration can be related with systemic diseases, local inflammation, or direct toxic action. In this chapter three corneal degenerations will be described: **Salzmann's nodular degeneration (SND), Terrien's marginal degeneration (TMD), and band keratopathy (BK). Arcus senilis** is not present in the developing due to benignant

allows direct measurements and comparison with prior scans (**Figure 5**).

*corneal Dellen can be considered stable during the last years.*

**24**

perforation [13].

nature of the disease.

**Figure 7.**

**Figure 6.**

*surgical management.*

**SND** is a noninflammatory, slowly progressive, degenerative corneal disease. It is characterized by the presence of elevated, bluish white to gray subepithelial nodules located in the anterior cornea**.** The size of the nodules oscillates from 1 to 2 mm. Nevertheless, larger nodules have been described as a result of the fusion of several smaller nodules [15, 16] (**Figure 8**).

SND was identified by Maximilian Salzmann in 1925. He described the corneal nodules, usually related to phlyctenular or atheromatous keratitis [17]. SND is often associated with chronic corneal inflammation and irritation. Multiple risk factors have been reported. Interstitial keratitis, vernal keratoconjunctivitis, dry eye disease, meibomian gland dysfunction, pterygium, soft contact lens wearers, and previous trauma or surgical procedures are some disorders that predispose to suffer the pathology.

SND usually occurs in female patients, ranging from 50 to 60 years old. Patients can present unilateral o bilateral disease (**Figure 8**). The number of nodules oscillates from one to eight. These nodules generally adopt a round shape. However, in some cases, they can be conical, prismatic, or wedge-like. Most nodules are avascular although some can be associated with blood vessels. They are normally located in the superior and inferior cornea. In cases of previous pterygium surgery, they will be often located in the edge of the blood vessels; in patients with history of contact lens wearing, in the interpalpebral portion; and in keratoconus patients, in the apex of the cornea.

Corneal AS-OCT SND images display prominent, hyper-reflective, subepithelial deposits overlying Bowman's membrane [1]. The corneal opacities are located under a normally reflective, thin epithelium [10, 16]. The intraepithelial fibrosis overgrowth can result in a corneal surface elevation above Bowman's layer. The central part of nodule has heterogeneous signal intensities, and the nodule margin can be differentiated by subepithelial triangle spike. An irregular stromal scarring can be seen below the nodules, limited to the stromal superficial layers. An epithelial hypertrophy may also be observed around the nodules in an attempt to regularize the corneal surface. The structure of the posterior stroma, Descemet's membrane, and endothelium is not affected by the fibrosis, but the AS-OCT imaging shows a modification of the posterior corneal curvature (**Figure 9**). Both modifications of anterior and posterior corneal curvature induce astigmatic changes and visual loss in these patients.

The destruction of Bowman's layer is considered the most important property in the pathophysiology of the disease [18]. Bowman's layer is replaced by a granular periodic acid Schiff-positive (PAS-positive) eosinophilic material that resembles

#### **Figure 8.**

*(A and B) AS slit-lamp biomicroscopy image shows the bluish to white nodules localized in the mid-peripheral inferior cornea. The corneal opacity is present in both eyes of a 56-year-old female SND patient.*

#### **Figure 9.**

*(A and C) AS slit-lamp biomicroscopy shows two nodules in the right eye of a female patient. (F, H, J) AS-OCT corneal scans display how the prominent nodules overgrow and produce a corneal anterior. (B and D) Corneal AS-OCT images demonstrate the SND nodules localized in the anterior corneal layers, destroying Bowman's layer and producing fibrosis in the anterior stroma. The nodules can be measured using the OCT caliper tool. The device allows the comparison of the nodules sizes between visits. (E, G, I) AS slit-lamp biomicroscopy demonstrates two nodules in the inferior corneal zone on the left eye of the same SND female patient. AS-OCT corneal scans display how the prominent nodules overgrow and produce a corneal anterior surface elevation. The corneal nodules are dense and hyper-reflective. An epithelial hypertrophy may also be observed around the nodules in an attempt to regularize the corneal surface. The structure of the posterior stroma, Descemet's membrane, and endothelium is not affected by the fibrosis, but AS-OCT imaging shows a modification of the posterior corneal curvature.*

a basement membrane. The progression of the pathology will be determined by Bowman's layer destruction (**Figure 10**). The involvement of the Bowman layer indicates that surgical delamination of the nodules may be more difficult.

Although most SND cases are asymptomatic, the symptoms can appear depending on the location of the nodules. When they are peripheral, the main symptom is a foreign body sensation, and when they are mid peripheral, the patients complain of decrease in visual acuity. The loss of vision can be attributed to the presence of the corneal opacity and modification of the corneal axis, resulting in an astigmatic change. Other referrals symptoms are severe pain, irritation, and epiphora. The peripheral nodules can produce a flattening of the central cornea, inducing a hyperopic change. This phenomenon has to be considered in the intraocular lens (IOL) power calculation previous to the cataract surgery. The corneal central flattening can cause a refractive postoperative miscalculation [17].

**27**

**Figure 11.**

**Figure 10.**

*subepithelial zone.*

*Clinical Application of Optical Coherence Tomography in the Corneal Degenerations*

*Corneal AS-OCT evaluation of a SND patient. The scans demonstrate Bowman's layer destruction by the nodule overgrowth. (A) A prominent nodule produces the corneal anterior surface deformation. (B and C) Another nodule extends superficially in the peripheral nasal cornea producing a hyper-reflective area in the* 

*(A–C) Digital AS slit-lamp biomicroscopy of a SND female patient. The nodules are present all around the peripheral cornea. (D) The same patient following a superficial keratectomy and alcohol-assisted epithelial* 

*delamination. The superficial corneal nodules have disappeared.*

*DOI: http://dx.doi.org/10.5772/intechopen.84244*

*Clinical Application of Optical Coherence Tomography in the Corneal Degenerations DOI: http://dx.doi.org/10.5772/intechopen.84244*

#### **Figure 10.**

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

a basement membrane. The progression of the pathology will be determined by Bowman's layer destruction (**Figure 10**). The involvement of the Bowman layer indicates that surgical delamination of the nodules may be more difficult.

*(A and C) AS slit-lamp biomicroscopy shows two nodules in the right eye of a female patient. (F, H, J) AS-OCT corneal scans display how the prominent nodules overgrow and produce a corneal anterior. (B and D) Corneal AS-OCT images demonstrate the SND nodules localized in the anterior corneal layers, destroying Bowman's layer and producing fibrosis in the anterior stroma. The nodules can be measured using the OCT caliper tool. The device allows the comparison of the nodules sizes between visits. (E, G, I) AS slit-lamp biomicroscopy demonstrates two nodules in the inferior corneal zone on the left eye of the same SND female patient. AS-OCT corneal scans display how the prominent nodules overgrow and produce a corneal anterior surface elevation. The corneal nodules are dense and hyper-reflective. An epithelial hypertrophy may also be observed around the nodules in an attempt to regularize the corneal surface. The structure of the posterior stroma, Descemet's membrane, and endothelium is not affected by the fibrosis, but AS-OCT imaging shows a* 

central flattening can cause a refractive postoperative miscalculation [17].

Although most SND cases are asymptomatic, the symptoms can appear depending on the location of the nodules. When they are peripheral, the main symptom is a foreign body sensation, and when they are mid peripheral, the patients complain of decrease in visual acuity. The loss of vision can be attributed to the presence of the corneal opacity and modification of the corneal axis, resulting in an astigmatic change. Other referrals symptoms are severe pain, irritation, and epiphora. The peripheral nodules can produce a flattening of the central cornea, inducing a hyperopic change. This phenomenon has to be considered in the intraocular lens (IOL) power calculation previous to the cataract surgery. The corneal

**26**

**Figure 9.**

*modification of the posterior corneal curvature.*

*Corneal AS-OCT evaluation of a SND patient. The scans demonstrate Bowman's layer destruction by the nodule overgrowth. (A) A prominent nodule produces the corneal anterior surface deformation. (B and C) Another nodule extends superficially in the peripheral nasal cornea producing a hyper-reflective area in the subepithelial zone.*

#### **Figure 11.**

*(A–C) Digital AS slit-lamp biomicroscopy of a SND female patient. The nodules are present all around the peripheral cornea. (D) The same patient following a superficial keratectomy and alcohol-assisted epithelial delamination. The superficial corneal nodules have disappeared.*

#### **Figure 12.**

*(A) Corneal AS-OCT analysis of the same SND female patient of Figure 11. (A, B, C) Hyper-reflective nodules can be seen in the mid- peripheral and inferior cornea. (D, E) Corneal AS-OCT scans from the same patient following superficial keratectomy and alcohol-assisted epithelial delamination. The nodules have been removed. The hyper-reflective corneal areas have disappeared, and the anterior surface has restored the morphology.*

In asymptomatic SND patients, conservative treatments will be enough to manage the pathology. The medical therapy with preservative-free lubricants and lid hygiene is appropriated. Autologous serum at 20–50% can be also used. In symptomatic patients, or when inflammation is present, an anti-inflammatory treatment is required. Topical cyclosporine 0.05%, topical preservative-free corticosteroids, and oral doxycycline are useful for the management of SND pathology.

Corneal surgical procedures will be required in persistent symptomatic nodules after medical therapy and in patients with a visual acuity decrease. The main techniques are superficial keratectomy (**Figures 11** and **12**) alone or followed by phototherapeutic keratectomy (PTK). Both procedures can be associated with alcohol-assisted epithelial delamination (**Figures 11** and **12**), amniotic membrane transplantation, or mitomycin-C application.

**29**

**Figure 14.**

*delamination. The hyper-reflective areas are not present.*

**Figure 13.**

*delamination technique.*

*Clinical Application of Optical Coherence Tomography in the Corneal Degenerations*

*AS slit-lamp biomicroscopy from a SND patient. (A, B, C) The fibrosis area can be seen in the nasal peripheral corneal zone. (D) The fibrosis has been removed by keratectomy and alcohol-assisted epithelial* 

*AS-OCT evaluation from the same SND patient of Figure 13. (A–C) The AS-OCT scans show a hyper-reflective zone in the fibrotic areas. (D and E) The fibrosis has been removed by keratectomy and alcohol-assisted epithelial* 

*DOI: http://dx.doi.org/10.5772/intechopen.84244*

*Clinical Application of Optical Coherence Tomography in the Corneal Degenerations DOI: http://dx.doi.org/10.5772/intechopen.84244*

#### **Figure 13.**

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

In asymptomatic SND patients, conservative treatments will be enough to manage the pathology. The medical therapy with preservative-free lubricants and lid hygiene is appropriated. Autologous serum at 20–50% can be also used. In symptomatic patients, or when inflammation is present, an anti-inflammatory treatment is required. Topical cyclosporine 0.05%, topical preservative-free corticosteroids, and oral doxycycline are useful for the management of SND pathology. Corneal surgical procedures will be required in persistent symptomatic nodules after medical therapy and in patients with a visual acuity decrease. The main techniques are superficial keratectomy (**Figures 11** and **12**) alone or followed by phototherapeutic keratectomy (PTK). Both procedures can be associated with alcohol-assisted epithelial delamination (**Figures 11** and **12**), amniotic membrane

*(A) Corneal AS-OCT analysis of the same SND female patient of Figure 11. (A, B, C) Hyper-reflective nodules can be seen in the mid- peripheral and inferior cornea. (D, E) Corneal AS-OCT scans from the same patient following superficial keratectomy and alcohol-assisted epithelial delamination. The nodules have been removed. The hyper-reflective corneal areas have disappeared, and the anterior surface has* 

**28**

**Figure 12.**

*restored the morphology.*

transplantation, or mitomycin-C application.

*AS slit-lamp biomicroscopy from a SND patient. (A, B, C) The fibrosis area can be seen in the nasal peripheral corneal zone. (D) The fibrosis has been removed by keratectomy and alcohol-assisted epithelial delamination technique.*

#### **Figure 14.**

*AS-OCT evaluation from the same SND patient of Figure 13. (A–C) The AS-OCT scans show a hyper-reflective zone in the fibrotic areas. (D and E) The fibrosis has been removed by keratectomy and alcohol-assisted epithelial delamination. The hyper-reflective areas are not present.*

Superficial keratectomy will be the surgical first-line therapy in most cases (**Figure 13**). The results will be conditioned by the degree of involvement of the superficial cornea and the degree of affection of the Bowman's layer described in the corneal AS-OCT images (**Figure 14**). An unbroken Bowman's layer or an altered Bowman's layer could be predictive of the strength of the adhesion of the nodules to the anterior stroma [16]. The method used to remove mechanically the opacities will be "peeling the nodules," referred in the bibliography as "Salzmann nodulectomy." In areas of excessive thinning, a careful manual dissection will be required [17].

Keratoplasty will be used in the most severe SND cases. Fortunately, as the mid stroma and Descemet membrane are intact in most SND cases, a lamellar keratoplasty (LK) will be enough to eliminate the opacities. Penetrating keratoplasty (PKP) will be rarely required in SND patients. PKP will be reserved for cases of intraoperative perforation during LK or full-thickness corneal alterations in association with another disease [17].

Corneal AS-OCT images in SND patients have an excellent correlation with the histopathologic exam. AS-OCT analysis is a useful technique that sustained SND diagnosis and helped the clinicians to decide the management and follow-up of the disease progression.
