Salzmann Nodular Degeneration in Ocular and Systemic Diseases.

This review aimed to evidence the predisposing conditions for Salzmann nodular degeneration (SND), where particular attention was paid to its association with ocular and systemic diseases. SND is a rare disease characterized by bluish-white nodules located in the mid-periphery of the cornea, which are otherwise completely clear. SND has been found in association with different systemic and ocular diseases, and it may have unilateral or bilateral presentation. Initial forms are only diagnosed occasionally as they are asymptomatic, whereas, in advanced disease, the visual acuity might be seriously impaired. Although SND is well described, its exact etiopathology is currently still unknown and is frequently misdiagnosed. It is associated with ocular surface inflammatory conditions and previous corneal surgery, and it has been described in different systemic diseases. Diagnosis is clinically based with slit lamp examinations, and instrumental assessments with corneal topography permit one to observe the alterations of the corneal profile, whereas anterior segment-optical coherence tomography (AS-OCT) is used to investigate the stromal depth of the nodules. Therapy might be conservative with the objective of improving the ocular surface homeostasis and surgical outcomes, where the aim is to restore the corneal regularity and visual acuity. Ophthalmologists should pay particular attention when detecting nodules in patients with ocular and non-ocular inflammatory diseases to guarantee the patient a timely diagnosis and a better therapeutic outcome. Additionally, collaboration between specialists who deal with treating patients suffering from disorders potentially associated with SND is recommended.

Combined superficial keratectomy, alcohol delamination and amniotic membrane patch with fibrin glue in Salzmann nodular degeneration.

PURPOSE: To describe the outcomes of five Salzmann's Nodular Degeneration (SND) cases treated with a combination of alcohol delamination, superficial keratectomy and amniotic membrane patch with fibrin glue. METHODS: Five patients affected by SND with significant discomfort and decreased visual acuity were evaluated with refraction, best corrected visual acuity, Break-up time test, corneal topography, Anterior Segment of Optical Coherence Tomography and images of anterior segment with a full slit lamp examination. All the patients underwent alcohol delamination of the corneal epithelium followed by superficial keratectomy to remove the subepithelial nodules. A patch of amniotic membrane was applied to all of them with a ring shape and a banana shape in two patients due to the location of the disease. A bandage contact lens was inserted. The patch was kept in place for 14 days. Another bandage contact lens was inserted for 21 days until the corneal epithelium had completely healed. RESULTS: The surgical procedure was successful in removing the nodules in all patients. Vision was restored in all cases with a significant regularization of the corneal surface and reduction of ocular discomfort. After a 12-month follow-up, none of the patients showed recurrence of the disease. CONCLUSIONS: Combining alcohol delamination with superficial keratectomy and amniotic membrane patch with fibrin glue is an effective procedure for the management of SND to regularize the corneal surface and avoid the recurrence of subsequent nodules. This report is the first description of the outcomes of SND cases treated with a combination of the aforementioned techniques.

Peripheral hypertrophic subepithelial corneal opacification - Role of tear secretion, medication and systemic diseases.

BACKGROUND: Peripheral hypertrophic subepithelial corneal opacification (PHSCO) is a corneal disease that may severely affect vision. The major goal of this study was to test the hypothesis that tear secretion, medication and systemic diseases are associated with PHSCO. METHODS: This is a retrospective, case-control study conducted at the Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz. We analysed medical records of patients diagnosed with PHSCO. Sex, age, Schirmer's test II, general medication and medical history were assessed and compared to an age- and sex-matched control group from the Gutenberg Health Study (GHS). RESULTS: One hundred ninety-five eyes of 112 patients with PHSCO were included. Eighty-eight patients were female with a mean age of 55.3 ± 14.7 years (23-89 years) and 24 patients were male with a mean age of 59.3 ± 12.6 years (38-84 years). In 83 patients (74.1%) both eyes were involved. The Schirmer's test II was significantly reduced in patients with PHSCO compared to the GHS control group (p < 0.001). Patients with PHSCO were more frequently administered artificial tears and steroid eye drops (p < 0.001) and were more hyperopic than healthy controls (p = 0.01). Systemic diseases or medication did not differ markedly between PHSCO and healthy controls. CONCLUSION: Reduced tear secretion and more frequent use of artificial tears in patients with PHSCO suggest a link between PHSCO and dry eye disease. The results of the study do not support our hypothesis that PHSCO is associated with systemic diseases. Interestingly, patients with PHSCO were less frequently on ß-blockers than control subjects.

Risk factors for peripheral hypertrophic subepithelial corneal opacification.

BACKGROUND: To evaluate the phenotype, tear secretion and refractive changes of patients diagnosed with peripheral hypertrophic subepithelial corneal opacification (PHSCO). METHODS: This is a retrospective, interventional case series conducted at the Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz. Medical records of patients diagnosed with PHSCO were analysed. Sex, age, fluorescein tear film breakup time (FTBUT), Schirmer Test II, iris colour and hair colour were assessed. Objective refraction was evaluated at different time points and, in case of surgery, 1 month and 1 year postoperatively. RESULTS: One hundred ninety-five eyes of 112 patients (78.6% female, 21.4% male; mean age 56.2 ± 14.3) were included. The median FTBUT was 6 sec. (Q1: 4/Q3: 8.75; range 1-20 s) (measured in 70 eyes of 36 patients), the median Schirmer Test II was 8 mm (Q1: 5/ Q3:15; range 1-35 mm). In 83 patients (74.1%) both eyes were involved. In 86 eyes of 64 patients (55.3%) superficial keratectomy was performed. Sphere and cylinder changed significantly 1 month and 1 year postoperative compared to the pre-operative objective refraction, while there was no significant change between 1 month and 1 year postoperatively. CONCLUSION: We found that PHSCO occurs mostly bilaterally in middle-aged women and appears to be associated with decreased tear production and reduced tear film stability.

Atypical Presentation of Salzmann Nodular Corneal Degeneration as a Subepithelial Corneal Dystrophy: A Case Report.

Salzmann nodular corneal degeneration (SNCD) is a rare, non-inflammatory, slowly progressive degenerative disease of the cornea. It is characterized by bluish-white nodules raised above the surface of the cornea. SNCD does not seem to consist of one clinical entity, which poses challenges to differentiate it from corneal dystrophies. A 20-year-old Chinese female with a history of eczema and dry eyes presented with a complaint of itchiness in both eyes, watery eyes, and gradual blurring of vision in the right eye for two years. Upon examination, right eye vision was counting fingers, whereas the left eye's best-corrected vision was 6/9. The anterior segment examination of the right eye showed generalized cornea haziness with superficial vascularization, while the left eye showed mild corneal haziness with no vascularization. Otherwise, both eyes had no signs of corneal infection, corneal scar, subepithelial nodular appearance, or allergic reactions, with no evidence of fluorescein staining. Anterior segment optical coherence tomography (AS-OCT) did not indicate subepithelial opacity. Subsequently, the patient underwent right eye superficial keratectomy under local anesthesia. Although clinically the patient was thought to have a form of subepithelial dystrophy, the histopathological report confirmed it to be SNCD. The best-corrected vision of the right eye improved to 6/12 post-keratectomy. We report an unusual presentation of Salzmann's corneal degeneration as subepithelial corneal haziness, which was treated successfully with superficial keratectomy.

Salzmann nodular degeneration in posterior keratoconus: a case report.

BACKGROUND: To report an unusual case of salzmann nodular degeneration (SND) in posterior keratoconus (PKC) after a corneal penetrating injury. CASE PRESENTATION: A 56-year-old woman presented with a history of recurrent light sensitivity, foreign body sensation, and tears after a corneal penetrating injury 20 years ago. The patient was diagnosed with SND accompanying with PKC by slit-lamp microscope, anterior segment optical coherence tomography (OCT), and corneal tomography. A combined therapy of medication (0.1% sodium hyaluronate eye drops, recombinant bovine basic fibroblast growth factor eye drops, and 0.1% fluorometholone eye drops) and bandage contact lens could not relieve the latest episode. A phototherapeutic keratectomy (PTK) treatment (laser ablation depth: 15 µm; treatment zone: 7.5 mm) was performed to remove nodules and smooth the surface. The best spectacle-corrected visual acuity improved from 20/63 preoperatively to 20/40 postoperatively. No SND relapse and corneal ectasia were recorded at follow-up 12 months later. CONCLUSIONS: This is the first known, reported case of SND accompanying with PKC after corneal trauma. The PTK is a safe and effective option for SND with PKC.

Superficial keratectomy followed by intense pulsed light for Salzmann's nodular degeneration and coexisting meibomian gland dysfunction.

PURPOSE: To describe the clinical course of a case of bilateral Salzmann nodular degeneration (SND) treated with superficial keratectomy (SK) followed by intense pulsed light (IPL) for the treatment of coexisting meibomian gland dysfunction (MGD). CASE DESCRIPTION: A 54-year-old man who presented to us complaining of progressive blurred vision associated with foreign body sensation in both eyes because of SND and coexisting MGD. In view of symptoms and visual acuity (VA) deterioration, bilateral SK was performed. Two months after SK, IPL treatment to the face and meibomian gland expression (MGX) using the E-eye device (E-SWIN, Paris) on days 0, 15, and 45, were performed in both eyes with the aim to avoid recurrence and/or progression of MGD. One year after SK, the patient was asymptomatic and VA was 20/20 in both eyes; however because of worsening of non-invasive tear film break-up time measured on Sirius® Scheimpflug tomograph, IPL and MGX were promptly repeated and scheduled every 6 months. CONCLUSION: In our case, IPL was a safe and effective option to control MGD in a patient with SND requiring SK with no observed recurrence of SND 2 years after surgery.

Atypical Presentation of Salzmann Nodule: A Case Report and Literature Review.

Salzmann's nodular degeneration (SND) is an unusual corneal condition that is slowly progressive and non-inflammatory in nature. It results in millimetric gray-white to bluish nodules formation anterior to Bowman's layer of the cornea. It usually affects both eyes in 80% of the cases. These elevated nodules are located near the limbus or in the mid-peripheral cornea, with some exceptions. Salzmann nodule develops following corneal trauma or inflammation. However, it can present idiopathically. Here, we report an atypical case of idiopathic symptomatic large central SND that was treated successfully with superficial keratectomy.

Corneal Nodules and Possible Pathologies: A Case Series.

Corneal nodular lesions are not uncommon in clinical practice. Diagnosing and managing this condition can be challenging due to its variable causes. This article highlights three cases of corneal nodular lesions. A common clinical pathway for the diagnosis and treatment of cornea nodular lesions is discussed. Two young females and an elderly man presented with a unilateral corneal nodule of variable duration, which was further demonstrated on anterior segment optical coherence tomography (AS-OCT). Several diagnoses were made after thorough history and examination which include herpetic stromal keratitis, phlyctenular keratoconjunctivitis secondary to blepharitis, and Salzmann nodular degeneration. All cases were initiated on topical antibiotics and topical steroids with additional medication or surgical procedure onboard according to their clinical condition. The corneal nodules resolved with scarring after a period of treatment. In conclusion, corneal nodular lesions can be associated with various pathologies. Thorough history, examination, and appropriate investigations are needed to reveal the underlying causes. Serial anterior segment images and AS-OCT are useful to monitor progression and treatment response. Prompt diagnosis and initiation of treatment are crucial to prevent further complications.

Salzmann's nodular degeneration.

Salzmann nodular corneal degeneration is a non-inflammatory, progressive corneal degeneration characterized by bluish-white nodules of varying shapes classically located in the mid-peripheral cornea. It was first described by Maximilian Salzmann in 1925 and was noted at that time to be associated with "eczematous keratoconjunctivitis". Since then, significant progress has been made to understand environmental and genetic risk factors associated with SND. However, etiopathogenesis remains poorly understood. A review of the literature was performed to highlight our recent understanding of SND and its management.

Myopic regression and recurrent Salzmann nodule degeneration after laser in situ keratomileusis in Ehlers Danlos Syndrome.

PURPOSE: We describe the first case of Ehlers Danlos Syndrome (EDS) reported in the English language ophthalmic literature to have undergone Laser In Situ Keratomileusis (LASIK) surgery. OBSERVATIONS: We review our patient's specific postoperative complications of myopic regression, Salzmann nodular degeneration, and dry eye syndrome, as well as the risks and consequences of performing LASIK on patients with this collagen disorder. CONCLUSIONS AND IMPORTANCE: Refractive errors may prompt EDS patients to seek laser vision correction, placing them at increased risk for complications such as myopic regression, keratectasia, and dry eye syndrome. Aberrant wound healing and collagen dysfunction may have influenced our patient's myopic regression and Salzmann nodule degeneration post-LASIK. Currently, EDS is considered a relative contraindication in LASIK due to a presumed higher risk of postoperative keratectasia; however, we believe it is possible that not all forms of EDS need to be an absolute contraindication to LASIK. More research is warranted to determine preoperative risk stratification for laser vision surgery in each subtype of EDS.

Successful surgical management of post-penetrating or deep lamellar keratoplasty Acquired Corneal Sub-Epithelial Hypertrophy (ACSH): A case series.

INTRODUCTION: Acquired Corneal Sub-Epithelial Hypertrophy (ACSH) has been described in patients with peripheral superficial corneal opacities following penetrating keratoplasty and might present similar to Salzmann's nodular degeneration (SND) or peripheral hypertrophic sub-epithelial corneal degeneration (PHSCD). We describe the clinical presentation, topographic findings and the surgical outcome of three cases, which fit the appearance and characteristics of ACSH. PRESENTATION OF CASES: Three patients (3 eyes) with paracentral or peripheral corneal opacification were reviewed to describe their clinical examination (SL), morphology of the opacity (depth, diameter and density) and document their topographic changes before and after surgical intervention by peeling of the epithelium with or without superficial keratectomy under the microscope in addition to brief description of their histopathological examination. DISCUSSION: All 3 cases were secondary to corneal procedures [Penetrating keratoplasty (PKP) in 1 for pseudophakic bullous keratopathy and deep anterior lamellar keratoplasty (DLK) in 2 for advanced keratoconus]. All cases presented with reduced vision, astigmatic changes in topography or manifest refraction. The visual acuity, symptoms, and topographical findings all improved after treatment. Histopathologically, all cases fit the newly described entity of ACSH. CONCLUSION: Careful clinical judgement guided by corneal topography are needed for proper the diagnosis of acquired corneal opacification that results in reduction of vision to identify ACSH from other similar conditions (PHSCD and SND). Peeling of the thickened epithelial and sub-epithelial tissue is curative avoiding the need for corneal re-grafting.

Phototherapeutic keratectomy.

Phototherapeutic keratectomy is an excimer laser-based surgical procedure widely performed by corneal surgeons for treating anterior corneal stromal pathologies. Phototherapeutic keratectomy helps by ablating the corneal stroma, thereby improving corneal clarity and smoothening the surface. Transient discomfort and induced hyperopia from corneal flattening are the immediate postoperative concerns. The long-term course is often marked by the recurrence of original corneal pathology and corneal haze formation. Phototherapeutic keratectomy, however, allows for repeat stromal ablation for managing recurrences, as the corneal thickness permits, without affecting the outcome of future keratoplasty. Adjunctive methods such as topical mitomycin-C may be additionally used to reduce recurrence rates. Also, various masking agents such as carboxymethyl cellulose, sodium hyaluronate, and dextran are used in eyes with irregular corneal surface to allow for uniform stromal ablation. Overall, phototherapeutic keratectomy has provided corneal surgeons an additional surgical tool, particularly those residing in developing nations where the availability of donor corneal tissue is an important limiting factor.

Successful Treatment of Corneal Opacification with Associated Thickened Epithelium by Simple Peeling: Acquired Corneal Subepithelial Hypertrophy (ACSH).

PURPOSE: To study clinical and histopathological findings of corneal opacification caused by thickened epithelium leading to reduced vision and topographical changes and to evaluate the outcome of its removal. METHODS: Twelve patients (17 eyes) with central, paracentral or peripheral corneal opacification were reviewed to obtain their visual acuity, describe their slit lamp (SL) appearance (depth, extent and density) and document their topographic changes before and after peeling of the epithelium under SL or surgical removal under the microscope. Specimens of six cases were available for histopathological examination and immunohistochemical staining. RESULTS: Most of the eye opacifications were secondary to corneal procedures in 10 [Penetrating keratoplasty (PKP) in 7 for congenital glaucoma, keratoconus or adherent leukoma - usually over graft-host junction -, Photorefractive keratectomy (PRK) in 2 and Phototherapeutic keratectomy in one], chronic inflammation following trachoma or non-specific causes (3), and herpetic scar (1). Three cases were considered to be idiopathic. All cases presented with decreased vision, astigmatism or changes in topography or refraction. Their vision, clinical symptoms and topography improved after treatment. Histopathologically, all six cases shared findings that are similar to what have been described as peripheral hypertrophic subepithelial corneal degeneration (PHSCD) rather than Salzmann's nodular degeneration. None of the cases showed inflammation or subepithelial pannus formation in the excised tissue. However, our cases did not fit into the diagnosis of PHSCD because of the location of the corneal opacification (being peripheral in 41% of the corneas, the presence of underlying primary etiologic factors in 82% of the eyes and the bilateral occurrence in 5 patients. CONCLUSIONS: Meticulous SL examination aided by corneal imaging may accurately diagnose and determine the depth of corneal opacification as a cause for reduced vision. Histopathologically, the removed tissue is similar to PHSCD, but cases differ in their clinical profile. Peeling the thickened epithelial/subepithelial tissue is curative in most patients, improves visual and clinical outcome and avoids unnecessary corneal grafting.

Salzmann nodular degeneration: prevalence, impact, and management strategies.

PURPOSE: This review will summarize the clinical and histological presentation of Salzmann nodular degeneration (SND), its prevalence and risk factors, potential underlying mechanisms, diagnostic tools, management options, and impact on cataract surgery and co-morbid ocular surface diseases. METHOD: PubMed review of 44 articles published between 1976 and 2018. RESULTS: SND is a corneal disease characterized by whitish gray or bluish nodules on the peripheral or central cornea. The clinical presentation of SND is variable and the nodules can be asymptomatic or cause foreign body sensation and/or blurred vision. Histologically, SND appears as subepithelial nodules with thin overlying epithelium, disrupted or absent Bowman's layer, and activated fibroblasts within the nodule. SND pathogenesis is not fully understood but is thought to involve poor epithelial protection and disruption of the epithelial-stromal interface, allowing for penetration of epithelially derived growth factors into the stroma and subsequent activation of stromal fibroblasts, eventually leading to sub-epithelial deposition of disorganized extracellular membrane components. SND most commonly occurs in Caucasian females in a bimodal distribution, occurring in the fifth or eighth and ninth decades of life. Risk factors for SND include ocular surface diseases and surgery. Surgical intervention is recommended in individuals with symptomatic nodules - primarily superficial keratectomy performed with or without intraoperative mitomycin C, photokeratectomy, and/or amniotic membrane transplantation. These procedures have been successful in removing the lesion and reducing corneal irregularity, but have variable recurrence rates (0-31%). CONCLUSION: The pathogenesis of SND is complex and multifactorial. Advances in diagnostic and treatment modalities have allowed for earlier and more accurate diagnosis and effective treatment of SND.

Salzmann's nodular degeneration of cornea associated with thyroid eye disease.

Salzmann's nodular degeneration (SND) typically occurs in patients who are female, 50-60 years old, and have a history of corneal inflammation and irritation. Multiple case reports have documented associations between SND and trachoma, viral infections, trauma, contact lens wear, corneal surgeries and corneal exposure. The authors describe a patient with bilateral SND confirmed by anterior segment optical coherence tomography (OCT) imaging in the context of thyroid eye disease (TED) and history of LASIK. Treatment involved propylthiouracil (PTU), artificial tear use, loteprednol etabonate ophthalmic gel, eyelid taping and selenium supplementation and prospective superficial keratectomy with diamond burr polish.

Visualization of corneal vascularization in peripheral hypertrophic subepithelial corneal opacification with OCT angiography.

PURPOSE: The major goal of this study was to test the hypothesis that in patients with peripheral hypertrophic subepithelial corneal opacification (PHSCO), visualization of corneal vessels is better with optical coherence tomography angiography (OCTA) than with conventional slit lamp microphotography. METHODS: Patients with PHSCO were included in this prospective study. The corneal findings were photographed using a slit lamp camera (Haag Streit BM 900® ) and visualized with anterior-segment OCT (Optovue XR Avanti, Fremont, California, USA). Additionally, OCTA with the Angiovue Imaging™ System was performed in the area of PHSCO. RESULTS: Thirty-four eyes of 19 patients (26% male and 74% female) with PHSCO were included in this study. In 21 eyes, vascularization in the area of PHSCO was visualized with the Angiovue-OCT, whereas only 10 eyes presented vessels in slit lamp photographs. CONCLUSION: Optical coherence tomography angiography allows better visualization of corneal neovascularization than slit lamp photography in patients with PHSCO. Corneal opacifications were found predominantly nasally, which was reflected by a local enlargement of corneal thickness.

Degeneración nodular de Salzmann / Salzmann's nodular degeneration

La degeneración nodular de Von Salzmann constituye una entidad clínico-patológica en la que aparecen nódulos lisos y opacos, blanco grisáceos o algo azulados en las capas anteriores de la córnea. La afectación suele ser bilateral y los nódulos tienden a disponerse en anillo sobre la media periferia corneal. Pueden estar relacionados o no con un proceso inflamatorio previo y su tratamiento puede ser sintomático o quirúrgico si compromete el área pupilar y con ella la visión del paciente.Se presenta un paciente masculino, de 57 años de edad, coloración de la piel blanca, quien acudió a la consulta y refirió enrojecimiento de ambos ojos (predominio del ojo derecho), con picor, escozor y lagrimeo, de más de 6 meses de evolución. Asociado a esto notó una zona de color blanquecina en ambos ojos. En la exploración oftalmológica se observaron lesiones blanquecinas sobrelevadas de aspecto hialino, en el tercio inferior de la córnea en el ojo derecho y en el ojo izquierdo hacia la región nasal. Se concluye que el caso presenta una degeneración nodular de Salzmann(AU)

Von Salzmann nodular degeneration constitutes a clinical pathological condition in which flat and opaque, white-grayish or bluish nodules appear in the anterior layers of the cornea. The effect is usually bilateral and the nodules tend to spread in a ring form upon the corneal peripheral media. It can be related or not with previous inflammatory process and its treatment can be symptomatic or surgical if the papillary area and the patient's vision are compromised. Here is the case of a 57 years-old male Caucasian patient, who went to the doctor´s and complained of reddened eyes (mainly the right eye), itching and tearing for more than six months. In addition to this, he observed a whitish area in both eyes. The eye screening showed overelevated whitish lesions of hyaline aspect in the lower third of the right eye cornea and in the left eye towards the nasal region. It was concluded that this is a case of Von Salzmann nodular degeneration(AU)

Salzmann's Nodular Degeneration.

Salzmann's nodular degeneration (SND) is a rare, noninflammatory, slowly progressive degenerative disease of the cornea that is characterized by the appearance of nodular bluish gray opacities that vary in number and size. It is usually bilateral; most commonly occurring in people aged 50-60 years old, with a female preponderance; and often associated with a history of prior corneal inflammation. The clinical features usually depend on the location of the nodules. Generally, the nodules of SND are bluish white to gray in color, 1-2 mm in size, and round, conical or prismatic in shape. The overlying Bowman's layer is usually absent from the nodular areas and is partially replaced by granular Periodic Acid Schiff-positive eosinophilic material resembling the basement membrane. Diagnostic investigations include ultrasonic pachymetry, anterior segment optical coherence tomography, ultrasound biomicroscopy, and confocal microscopy. The majority of patients respond well to conservative management with topical lubricants; severe cases may require surgical intervention. The various surgical modalities described include superficial keratectomy, which may be combined with phototherapeutic keratectomy and keratoplasty. Various modifications of these procedures include the use of alcohol-assisted epithelial delamination, intraoperative mitomycin-C or amniotic membrane transplantation to make the procedure easy, reduce the risk of recurrence and improve postoperative comfort. Recurrences are rarely reported; overall, the visual prognosis following treatment is optimal.