Signs and Symptoms

Patients with Salzmann’s nodular degeneration are often asymptomatic, particularly in the early stages of the disease. Some may present with subjective glare, photophobia or diminished visual acuity if the nodules are situated on or near the visual axis.1,2 Nonspecific dry eye complaints such as burning, grittiness and foreign body sensation may also be reported.2,3 Eyes with more advanced disease are prone to intermittent bouts of recurrent corneal erosion. During these episodes, patients may experience pronounced discomfort, photophobia, blepharospasm and excessive tearing.1

Clinically, Salzmann’s degeneration appears as an accumulation of round to oval, bluish-white (and sometimes creamy, yellowish-white) subepithelial corneal nodules, often arranged in an annular fashion.1,2 Most commonly, the nodules are situated in the mid-peripheral cornea, but central and peripheral lesions have also been noted.2 Vascularization of Salzmann’s nodules is likewise variable. The condition is non-inflammatory in nature; hence, the involved eye is typically white and quiet, unless there is associated corneal erosion. In that event, there will be limbal injection, corneal edema and an anterior chamber reaction. Most patients with Salzmann’s degeneration appear to have bilateral involvement, with two large retrospective series reporting bilateral disease in approximately 66% and 63% of cases, respectively.2,3 The condition affects various ages and races, but usually presents in the sixth decade of life, and appears to be encountered more frequently in women than in men.1-3


Although the precise etiology of Salzmann’s degeneration has not been clearly determined, the prevailing theory is that chronic irritation to the ocular surface or a history of corneal trauma is involved in the pathogenesis.2 Most patients can relate a history of prior trauma, surgery or other ocular inflammation, which may predate the corneal manifestations by a number of years.1,3 Associated disorders include phlyctenular disease, meibomian gland dysfunction (including ocular rosacea), vernal keratoconjunctivitis, trachoma or interstitial keratitis.1-7 Additionally, patients with a history of epithelial basement membrane dystrophy, rigid contact lens wear, keratoconus, filamentary keratitis, chemical (or thermal) trauma, LASIK and incisional corneal surgery are all regarded as having increased risk.1-7 The inflammation associated with these disorders appears to provoke histopathologic and functional changes at the level of the superficial stroma, particularly Bowman’s layer. This initiates a cascade of changes that produces the disease’s signs and symptoms.1,3,8-10

At the cellular level, the nodules seen in Salzmann’s degeneration consist of collagen fibers and extracellular material at the anterior stroma.2 They display reduced cell density and a hyaline-like appearance.11 Oxytalan fibers, which are present in other degenerative corneal disorders such as keratoconus and Fuchs’ endothelial dystrophy, have also been identified in Salzmann’s nodular degeneration.9 As the condition progresses, there is subsequent degradation of Bowman’s layer in the areas that overlie the nodules. The normal architecture is replaced by an accumulation of a basement membrane-like substance. The corneal epithelium associated with these areas thins accordingly. In some specimens, only a single layer of flattened squamous cells remains.2 Descemet’s membrane and the corneal endothelium characteristically remain intact. With proliferation of the nodules, there is widespread disorganization of the cornea’s epithelial basement membrane. This predisposes these patients to painful epithelial erosions.3


It has been suggested that asymptomatic patients with Salzmann’s degeneration require no therapy.1,12 However, since chronic low-grade irritation of the ocular surface has been proposed as a driving force in the disease’s development and progression, it seems reasonable and appropriate to employ topical lubricants as first-line therapy.2 In two large series examining patients with Salzmann’s nodular degeneration, a favorable response to conservative medical therapy (i.e., artificial tears, lid hygiene and oral doxycycline for associated meibomian gland dysfunction) was noted in 72% and 68% of cases, respectively.2,3 These individuals did not require further surgical intervention.

Patients with associated corneal erosions require specific treatment aimed at diminishing pain and promoting re-epithelialization. This is best accomplished with cycloplegia (e.g., 5% homatropine BID) and topical nonsteroidal anti-inflammatory agents (e.g., 0.45% ketorolac tromethamine BID), as well as prophylactic, broad-spectrum antibiotics and copious lubrication. Additionally, some sources recommend therapeutic bandage contact lenses in cases of recurrent corneal erosion.13-15 Human amniotic membrane may also be beneficial in the rehabilitation of such cases.16

Corneal surgery may be warranted for more severe, recalcitrant or symptomatic disease. The most common indication for surgical intervention is visual disturbance, followed by subjective discomfort associated with recurrent corneal erosions.2,3 Superficial keratectomy is beneficial in cases of subepithelial lesions on or near the visual axis, or for midperipheral lesions inducing irregular astigmatism.1 Phototherapeutic keratectomy (PTK) performed with an excimer laser is another option. PTK has been shown to enhance visual function by improving contrast sensitivity while decreasing higher-order aberrations.13 Because these procedures have the potential for scar formation, incomplete resolutions or both, most surgeons today employ an antimetabolite agent, which has been shown to greatly improve outcomes.17-19

Alternatively, individuals who are unwilling or unable to endure surgery may derive some benefit from the use of custom fitted corneal, hybrid or scleral contact lenses. A recent study evaluated the use of the PROSE (Prosthetic Replacement of the Ocular Surface Ecosystem, BostonSight) system on a small group of patients with Salzmann’s nodular degeneration who were unsuccessful with conventional therapy and who also elected not to undergo traditional surgical offerings. The results were encouraging, demonstrating a statistically significant improvement in visual acuity and ocular surface symptomology.20

In advanced cases of Salzmann’s degeneration where central or deep stromal scarring is present, or if chronic epithelial breakdown makes the condition otherwise unmanageable, lamellar or penetrating keratoplasty may be the only recourse for restoration of vision.1 Still, recurrence is possible; though exceedingly rare, several publications have described the regeneration of Salzmann’s nodules in donor corneas several years after penetrating keratoplasty.12,21,22

Clinical Pearls

The critical issue in managing Salzmann’s degeneration is proper diagnosis. Conditions such as band keratopathy, spheroid degeneration (i.e., climatic droplet keratopathy) and corneal keloids may all present with a similar clinical appearance. Consultation with a corneal specialist is advisable in those cases where the diagnosis is equivocal.

Refractive changes may precede or complicate visual compromise associated with Salzmann’s nodular degeneration. The peripheral location of the nodules can induce flattening of the central cornea, resulting in a hyperopic shift.16,19 Irregular corneal astigmatism has also been noted on topographic analysis.16,20

It may be tempting to use topical corticosteroids in Salzmann’s degeneration, particularly if the patient is symptomatic. However, since this condition is noninflammatory in nature, steroids are merely palliative and do not alter the progression of the disease; additionally, their use introduces unnecessary risks such as elevation of intraocular pressure, cataracts and secondary infection.

1. Das S, Link B, Seitz B. Salzmann’s nodular degeneration of the cornea: a review and case series. Cornea. 2005;24(7):772-7.

2. Graue-Hernández EO, Mannis MJ, Eliasieh K, et al. Salzmann nodular degeneration. Cornea. 2010;29(3):283-9.

3. Farjo AA, Halperin GI, Syed N, et al. Salzmann’s nodular corneal degeneration clinical characteristics and surgical outcomes. Cornea. 2006;25(1):11-5.

4. Katz D. Salzmann’s nodular corneal dystrophy. Acta Ophthalmol. 1953;31(4):377-83.

5. Werner LP, Issid K, Werner LP, et al. Salzmann’s corneal degeneration associated with epithelial basement membrane dystrophy. Cornea. 2000;19(1):121-3.

6. Stem MS, Hood CT. Salzmann nodular degeneration associated with epithelial ingrowth after LASIK treated with superficial keratectomy. BMJ Case Rep. 2015;pii:bcr2014207776.

7. Moshirfar M, Chang JC, Mamalis N. Salzmann nodular degeneration after laser in situ keratomileusis. Cornea. 2010;29(7):840-1.

8. Frising M, Pitz S, Olbert D, et al. Is hyaline degeneration of the cornea a precursor of Salzmann’s corneal degeneration? Br J Ophthalmol. 2003;87(7):922-3.

9. Obata H, Inoki T, Tsuru T. Identification of oxytalan fibers in Salzmann’s nodular degeneration. Cornea. 2006;25(5):586-9.

10. Stone DU, Astley RA, Shaver RP, Chodosh J. Histopathology of Salzmann nodular corneal degeneration. Cornea. 2008;27(2):148-51.

11. Meltendorf C, Bühren J, Bug R, et al. Correlation between clinical in vivo confocal microscopic and ex vivo histopathologic findings of Salzmann nodular degeneration. Cornea. 2006;25(6):734-8.

12. Yoon KC, Park YG. Recurrent Salzmann’s nodular degeneration. Jpn J Ophthalmol. 2003:47(4):401-4.

13. Ozkurt Y, Rodop O, Oral Y, et al. Therapeutic applications of lotrafilcon a silicone hydrogel soft contact lenses. Eye Contact Lens. 2005;31(6):268-9.

14. Fraunfelder FW, Cabezas M. Treatment of recurrent corneal erosion by extended-wear bandage contact lens. Cornea. 2011;30(2):164-6.

15. Moutray TN, Frazer DG, Jackson AJ. Recurrent erosion syndrome—the patient’s perspective. Cont Lens Anterior Eye. 2011;34(3):139-43.

16. Huang Y, Sheha H, Tseng SCG. Self-retained amniotic membrane transplantation for recurrent corneal erosion. J Clin Exp Ophthalmol. 2013;4:272.

17. Bowers PJ Jr, Price MO, Zeldes SS, Price FW Jr. Superficial keratectomy with mitomycin-C for the treatment of Salzmann’s nodules. J Cataract Refract Surg. 2003;29(7):1302-6.

18. Marcon AS, Rapuano CJ. Excimer laser phototherapeutic keratectomy retreatment of anterior basement membrane dystrophy and Salzmann’s nodular degeneration with topical mitomycin C. Cornea. 2002;21(8):828-30.

19. Reddy JC, Rapuano CJ, Felipe AF, et al. Quality of vision after excimer laser phototherapeutic keratectomy with intraoperative mitomycin-C for Salzmann nodular degeneration. Eye Contact Lens. 2014;40(4):213-9.

20. Chiu GB, Bach D, Theophanous C, Heur M. Prosthetic Replacement of the Ocular Surface Ecosystem (PROSE) scleral lens for Salzmann’s nodular degeneration. Saudi J Ophthalmol. 2014;28(3):203-6.

21. Severin M, Kirchhof B. Recurrent Salzmann’s corneal degeneration. Graefes Arch Clin Exp Ophthalmol. 1990;228(2):101-4.

22. Sinha R, Chhabra MS, Vajpayee RB, et al. Recurrent Salzmann’s nodular degeneration: report of two cases and review of literature. Indian J Ophthalmol. 2006;54(3):201-2.

23. Oster JG, Steinert RF, Hogan RN. Reduction of hyperopia associated with manual excision of Salzmann’s nodular degeneration. J Refract Surg. 2001;17(4):466-9.

24. Reinshagen H. Salzmann’s nodular corneal degeneration—a case report. Klin Monbl Augenheilkd. 2014;231(4):325-6.