Salzmann’s Nodular Degeneration is a non-inflammatory, degenerative process characterised by whitish-grey or bluish-white elevated sub-epithelial nodules in the superficial corneal stroma that are usually bilateral, mid-peripheral and slowly progressive. There is usually a clear area before the limbus. It can cause blurred vision if it occurs in central part blocking the visual axis. It occurs more often in women than in men. The nodules elevate the epithelium. Peripheral lesions tend to be vascularised and may look like pseudopterygium.
Salzmann described it as a dystrophy (genetic disorders characterised by deposition of abnormal material in cornea) in 1925, but it is a degenerative change that usually occurs years after some inflammatory condition of the cornea. He described it in association with keratoconjunctivitis, but with time, several different disorders coexisting with this degeneration were detected. To date, its aetiopathogenesis remains unknown, but it is considered to be associated with ocular surface inflammation or chronic trauma. The onset of the lesions is gradual and often occurs many years after the keratitis. The antecedent eye disease usually occurs in childhood. However, several cases with no previous corneal pathology have been reported and are considered idiopathic.
There are, usually one to nine discrete para-central lesions, often in a circular array at areas of corneal scarring or at the junction of old corneal scars and clear cornea. Each nodule is separated from other nodules by clear cornea, and iron lines may outline each nodule. The underlying stroma may be vascularised but the nodules are not vascularised.
Agarwal Sunita, Agarwal Athiya, Apple David J, Buratto Lucio, Alio Jorge L, Pandey Suresh K and Agarwal Amar. Textbook of Ophthalmology Volume 1. First Edition. Jaypee Brothers Medical Publishers (P) Ltd.. 2002. New Delhi. P. 1082.
Basak Samar K. Atlas of Clinical Ophthalmology. Second Edition. Jaypee Brothers Medical Publishers (P) Ltd. 2013. P 119.
Kanski Jack J, Bowling Brad. Synopsis of Clinical Ophthalmology. Third Edition. Elsevier Saunders. 2013. P 121.
Salzmann M. Ueber eine Abart der Knotchenformigen Hornhautdystrohie. Z Augenheilkd. 1925; 57: 92-99. German.
Many patients with Salzmann’s nodular degeneration are asymptomatic.
Symptomatic patients may complain of:
Though the aetiology remains uncertain in majority of the cases, it is hypothesized that Salzmann’s nodular degeneration can be triggered by multiple events that lead to a nonspecific corneal tissue reaction based on individual predisposition. It appears to be more frequent in middle-aged women, and may be bilateral in about 60% of cases.
Ocular surface disorders:
Recently, Salzmann’s nodular degeneration in patients with Crohn’s disease was reported, and a hypothesis about association with systemic diseases was contemplated.
Genetic causes have also been described.
One of the hypotheses suggests that enzymatic destruction of Bowman’s membrane results in migration and proliferation of keratocytes from the stroma, resulting in secondary deposition of extracellular matrix components in nodular areas.
Histopathological studies have shown that the corneal nodules are located in sub-epithelium, but may extend to one-third of the anterior stroma and are formed by a dense connective tissue with hyaline degeneration. The corneal epithelium has an irregular thickness, with extremely increased thinning over the corneal nodules. The Bowman’s membrane exhibits disruption, may no longer be appreciable, and frequently replaced by fibrosis. Sub-epithelial fibrosis is a frequent histopathological finding, with activated fibroblasts beneath the epithelial cells. Increased expression of matrix metalloproteinase-2 (MMP-2) was recently detected in patients affected by Salzmann’s nodular degeneration, and this may be responsible for the induction of the basement membrane and Bowman’s membrane disruption.
Immunohistochemical analysis of protein expression in the basal epithelial cells suggests a high metabolic activity. This finding implicates the involvement of the epithelial cells in the formation of the sub-epithelial collagen elements seen in nodules. This in turn correlates with the clinical association linking corneal epithelial disease with the development of nodular degeneration.
Autoimmune aetiology has also been suggested in terms of pathogenesis of nodular degeneration.
Diagnosis of Salzmann’s nodular degeneration is usually made clinically.
The patients usually present with gradual, painless loss of vision for both near and distance. The combination of corneal nodules, corneal surface irregularities, and associated refractive error may lead to visual impairment. Visual impairment is progressive and due to an astigmatic defect produced by the nodules. Severe corneal irregularities in advanced stages generate high irregular astigmatism with severe visual loss. Patients may complain of reduced vision if the nodules are located in the central cornea.
There may or may not be a history of chronic ocular surface disease. Patients may also complain of a foreign body sensation on the surface of the eye. Elevated nodules can cause discomfort and epithelial erosions.
Typical clinical signs could be observed during Slit lamp (biomicroscopic) examination by an eye specialist.
Corneal topography demonstrates the irregularities of the corneal shape produced by corneal nodules, and the induced surface alteration depends on their number and localisation.
Anterior segment- Optical coherence tomography (AS-OCT):
Anterior segment- Optical coherence tomography (AS-OCT) allows the evaluation of dimension and depth of nodules, showing stromal extension that can help decide the surgical approach.
In vivo confocal microscopy:
In vivo confocal microscopy shows normal epithelium in the central cornea with rare sub-basal nerve fibers that display increased thickness with lack of branching. Nerve fibers in corneal stroma are also abnormal in that their branches are very thick and tortuous with highly reflective segments. These stromal nerves resemble regenerating nerves as are seen after penetrating keratoplasty. Deep stroma and endothelium do not appear to be altered. The peripheral zone of the nodules displays basal epithelial cells that appear abnormally elongated. Confocal microscopy showed an increased reflectivity of the anterior stroma and marked stromal scatter corresponding to the nodules, as a result of the presence of fibrosis. Highly reflective structures representing activated keratocytes are present in both peripheral zone and in the sub-epithelial stroma of the central portion of the nodules.
Salzmann’s nodular degeneration may be differentiated from similar conditions resulting in deterioration of vision such as:
Management should be carried out under medical supervision.
Many elderly patients who have peripheral Salzmann’s nodules are asymptomatic and do not require any treatment.
Salzmann’s nodular degeneration usually does not resolve spontaneously. Depending upon the clinical picture, medical therapy or surgical therapy is required. Surgical therapy, when indicated, usually results in rapid improvement of visual acuity.
Any potential underlying aetiology should be managed accordingly.
Medical therapy, successfully treats most patients, and may include:
Indications for surgical therapy are:
Surgical procedures are:
The recurrent lesions are often not clinically similar to the original lesions but are indistinguishable histologically.
The recurrence of Salzmann’s nodules after surgical removal can occur with varying prevalence rates and periods of time.
Prognosis is very good to excellent. Visual disturbance is relieved by lamellar keratectomy. The condition may recur after surgical excision.
Complications of Salzmann’s nodular degeneration: