The gold standard to diagnose a PUK is currently the slit lamp examination.1 Monitoring the disease activity by clinical examination alone can be challenging, as the evaluation of the corneal thinning and fluorescein staining in the setting of an inflammatory irregular stroma remains difficult and subjective. Our study demonstrates the benefits of AS-OCT in the diagnosis and the monitoring of PUK. It allowed an accurate localization of the epithelial defect and a measurement of the corneal depth involved. An objective monitoring of the epithelial thickness evolution was also achieved. Findings of the healing process, with epithelial morphologic changes, thickening and filling the thinned area that may be too subtle to be seen clinically were also assessed by AS-OCT.
Anterior-segment OCT findings were useful to recognize early recurrences before they manifested clinically. The surveillance of the level of disease activity is meaningful as PUK can be associated with life threatening situations in the context of systemic diseases.4,11 Detecting discrete anatomical signs of increased disease activity led to an intensification of immunosuppressive therapy to prevent corneal perforation or death. In a field with a low level of evidence-based guidelines for the management of PUK, making therapeutic decisions based on AS-OCT findings was helpful.12 We therefore recommend the use of AS-OCT as an adjunctive objective tool in the diagnosis and management of PUK.
Other peripheral corneal lesions, infectious or inflammatory, can mimic a PUK, and AS-OCT has been shown to be helpful in allowing an accurate diagnosis. For example, its usefulness in the setting of infectious keratitis has been described, with specific AS-OCT features such as retrocorneal plaques and stromal necrosis.13-14 This may help to make a diagnosis when the slit-lamp examination itself remains limited because of corneal opacification.13 Adding our specific findings, the evaluation of complex peripheral inflammatory disease process which are clinically difficult to differentiate, can be improved by AS-OCT.
In our series the diagnosis of PUK was certain as laboratory work-up found a systemic vasculitis in all cases, whereas classically 50% of PUK cases have an associated collagen vascular disease.6 Our findings are the first step towards a better classification using AS-OCT of the peripheral corneal inflammatory lesions’ spectrum, making progress towards standardization of their diagnosis and management, a difficult goal in rare diseases.
Anterior segment OCT has become an important tool in the evaluation and management of many corneal and anterior segment diseases, allowing a detailed evaluation in a non-contact and safe way.9 In cases of ocular surface lesions, close correlation between AS-OCT and histopathology findings have been confirmed that allowing AS-OCT to serve as an adjunctive diagnosis modality.14 In cases of PUK, histological diagnosis is not easily accessible.15 Confocal microscopy could also be helpful, with its resolution of 1 µm /pixel, as it could provide images comparable to histochemical methods, thus enabling the study of epithelial cells and stromal keratocytes.16
Using these imaging techniques, a better understanding of the pathophysiology of PUK can be achieved. The mechanisms of keratolysis are complex and currently poorly understood. The peripheral cornea and limbus reside close to conjunctival blood vessels and lymphatic channels, and with more Langherans cells and C1 components than the central cornea, are an ideal area for immune complex deposition as signs of active collagen vascular disease.15 These depositions could result in activation of metalloproteinases (MMP -type one, two and nine-) and collagenases by inflammatory cells and adjacent conjunctival tissue, and have been found in patients with PUK.17,18 Another proposed mechanism for development of PUK centers around the alterations in the conjunctival vascular structure. Varying degrees of vaso-occlusion of the episcleral and conjunctival vasculature have been demonstrated in patients with PUK.19 This vasculopathy may lead to resorption of stromal tissue, resulting in peripheral corneal ulceration and necrosis.11 The scrambled appearance at the anterior stroma seen on our AS-OCT during the active stage could be either residual fragments of epithelial cells or stromal anterior keratocytes. Depending on the level of disease activity, this appearance could also be either digested epithelial cells or keratocytes by MMP, or ischemic necrotic cells by vaso-occlusion, or a combination of both mechanisms. Likely, the pathophysiology of PUK is multifactorial, and further studies with larger samples and prospective AS-OCT image acquisition is needed to strengthen our understanding of the disease process and to further define the role of AS-OCT in the diagnosis and management of PUK.
This paper has several limitations, including its retrospective nature and small size. Description of AS-OCT findings was limited to the qualitative anatomical changes that occurred in the epithelial and the stromal layers during the different stages of the disease. We did not perform epithelial thickness measurements, as the anterior-segment module of OCT we used did not have a follow-up mode, limiting the reproducibility of imaging acquisition. For a better understanding of the disease, further prospective studies are necessary to quantify epithelial and stromal thicknesses changes objectively at different stages of the disease.