Establishing an objective biomarker for corneal cystinosis using a threshold‐based Spectral domain optical coherence tomography imaging algorithm

Abstract

Purpose The purpose of the present study was to establish a semi‐automated threshold‐based image segmentation algorithm to detect and objectively quantify corneal cystine crystal deposition in ocular cystinosis with anterior segment optical coherence tomography (AS‐OCT). Methods This prospective, observational, comparative study included 88 eyes of 45 patients from the German Cystinosis Registry Study as well as 68 eyes of 35 healthy control subjects. All eyes were imaged with AS‐OCT (Cirrus HD‐OCT 5000, Carl Zeiss Meditec AG, Jena, Germany). As an initial step, B‐scan images were subjectively analysed for typical changes in morphology in comparison to healthy controls. Based on the experience gained, an objective semi‐automated B‐scan image segmentation algorithm was developed using a grey scale value‐based threshold method to automatically quantify corneal crystals. Results On AS‐OCT B‐scans, corneal crystals appeared as hyperreflective deposits within the corneal stroma. The crystals were distributed either in all stromal layers (43 eyes, 49%) or confined to the anterior (23 eyes, 26%) or posterior stroma (22 eyes, 25%), respectively. The novel automatic B‐scan image segmentation algorithm was most efficient in delineating corneal crystals at higher grey scale thresholds (e.g. 226 of a maximum of 255). Significant differences in suprathreshold grey scale pixels were observable between cystinosis patients and healthy controls (p < 0.001). In addition, the algorithm was able to detect an age‐dependent depth distribution profile of crystal deposition. Conclusion Objective quantification of corneal cystine crystal deposition is feasible with AS‐OCT and can serve as a novel biomarker for ocular disease control and topical treatment monitoring.

Corneal Manifestation in Patients with Infantile Nephropathic Cystinosis

“…Using AS-OCT, Keidel et al developed a semiautomated B-scan image segmentation algorithm to objectively grade cornea crystal depth and proposed a novel biomarker for disease control and topical treatment monitoring (▶ Fig. 3) [22].…”

Spectral domain optical coherence tomography-based retinochoroidal cystine crystal score: a window into infantile nephropathic cystinosis

“… 5 For objective grading of the corneal crystals, a semiautomated grey scale system was developed using anterior segment optical coherence tomography (Cirrus HD-OCT 5000, Carl Zeiss Meditec AG, Jena, Germany) and applied as described previously. 6 The CCCS, on the other hand, is a subjective 13-step grading system based on a library of slit-lamp photographs of corneas with increasing crystal density. The assessment is made by subjective image comparison with an online photo atlas.…”

Ciszteamintartalmú szemcsepp alkalmazása cystinosisban

“…Feltételezhető, hogy a viszkózus formának köszönhetően hosszabb ideig a szemfelszínen maradó hatóanyag a cornea rétegeibe felszívódva nagyobb koncentrációt ér el a szaruhártya elülső rétegeiben a hátsó rétegekhez viszonyítva, így ezen a területen fokozottabb a cisztinkristályok feloldódása. Cystinosisban a kristálylerakódás a szaruhártya elülső rétegeiben indul, majd később a hátsóbb rétegek is érintetté válnak [18,19]. Így a viszkózus állagú készítmény minél korábbi életkorban való alkalmazása és ezáltal a szaruhártya elülső rétegeiben lerakódott kristálymennyiség hatékony csökkentése feltehetően hozzájárul a cornealis érintettség mértékének enyhítéséhez.…”