Optical coherence tomography for presurgical delineation of basal cell carcinomas on the face-A comparison with histopathology.

BACKGROUND: To minimize the risk of incomplete excision of basal cell carcinomas (BCC) the macroscopic tumor margins should be adequately defined. Optical coherence tomography (OCT) is a non-invasive imaging tool that can provide structural and vascular information about skin cancer lesions. The study objective was to compare the presurgical delineation of facial BCC by clinical examination, histopathology, and OCT imaging in tumors undergoing full excision. METHODS: Ten patients with BCC lesions on the face were examined clinically, with OCT and histopathology at 3-mm intervals, from the clinical lesion border and beyond the resection line. The OCT scans were evaluated blinded and a delineation estimate of each BCC lesion was made. The results were compared to the clinical and histopathologic results. RESULTS: OCT evaluations and histopathology were in agreement in 86.6% of the collected data points. In three cases the OCT scans estimated a reduction of the tumor size compared to the clinical tumor border set by the surgeon. CONCLUSION: The results of this study support the notion that OCT can have a role in the clinical daily practice by aiding clinicians in delineating BCC lesions before surgery.

Dynamic optical coherence tomography shows characteristic alterations of blood vessels in malignant melanoma.

BACKGROUND: Dynamic optical coherence tomography (D-OCT) allows in vivo visualization of blood vessels in the skin and in malignant tumours. Vessel patterns in malignant melanoma may be associated with tumour stage. OBJECTIVE: The aim of this study was to describe blood vessel patterns in melanomas and to correlate them with stage. METHODS: One hundred fifty-nine malignant melanomas were assessed in a multicentre study. Every tumour was imaged using D-OCT prior to surgery and histologic evaluation. The tumour data such as thickness and ulceration as well as the staging at primary diagnosis and a follow-up of at least 40 months resulted in a stage classification. The vessel patterns were assessed according to predefined categories, compared with healthy adjacent skin, and correlated to stage. RESULTS: Melanomas contained more blood vessels in different patterns compared with healthy adjacent skin. In particular, irregular vascular shapes such as blobs, coils, curves and serpiginous vessels were more common in melanomas. In addition, these patterns were significantly more often found in high-risk and metastatic melanomas than in low-risk lesions. CONCLUSION: In melanomas, the density of the blood vessels is increased, and irregular vascular patterns are more frequent. At higher stages, especially in metastatic melanomas, these atypical vessels are significantly more common.

Dynamic optical coherence tomography of histamine induced wheals.

BACKGROUND: Dynamic optical coherence tomography (D-OCT) is a noninvasive imaging technique providing images of the skin and detecting movement in the tissue ie, measuring blood flow. The "attenuation coefficient" describes light absorption and scattering abilities of the tissue, while the dynamic signal provides a quantitative measure of the blood flow. AIM: The study objective is to describe the dynamic changes of the skin and skin vessels during histamine release using D-OCT. METHODS: Healthy volunteers had local histamine injections in the skin and D-OCT-scans performed at 2-minute intervals to detect changes in blood flow, attenuation and clinical symptoms. RESULTS: 9/10 participants showed clinical wheals. An increase in blood flow was shown at all depths (P < .001 at 2 minutes). The highest relative increase was seen at 300 µm. The signal at 500 µm decreased to insignificant values and remained low after 4 minutes. A decrease in visualization depth of up to 32.7% as well as a significant increase in the attenuation coefficient was shown (P < .001 at 12 minutes for both tests). CONCLUSION: Dynamic optical coherence tomography is able to reliably identify changes in blood flow of histamine induced wheals. Dermal oedema reduces visualization depth and increases the attenuation coefficient.

In vivo measurements of blood vessels' distribution in non-melanoma skin cancer by dynamic optical coherence tomography - a new quantitative measure?

BACKGROUND: Skin biopsies only provide point-in-time data making longitudinal studies difficult. Using Dynamic optical coherence tomography (D-OCT) in vivo, non-invasive imaging of the microvasculature becomes possible. The current OCT literature is almost exclusively based on qualitative information but quantitative data may offer additional advantages, for example, by reducing observer variation. The objective of this study was to evaluate the in vivo superficial distribution of blood vessels, defined as the surface-to-first-vessel distance, in actinic keratosis, basal cell carcinoma, squamous cell carcinoma and normal skin. METHODS: D-OCT images of 52 histologically verified lesions and corresponding normal skin were included. The dataset consisted of 13 AK, 22 BCC and 17 SCC. No tumour sub-classification was done. RESULTS: The quantitative measurement of the surface-to-first-vessel distance showed a significant difference between NMSC and corresponding normal skin. Significant differences were also seen for BCC, and it is hypothesized that the measure may also be able to distinguish between AK and SCC (borderline significant differences). CONCLUSION: Our results could prove useful in discriminating between non-melanoma skin cancer lesions and healthy skin and in making a specific diagnosis. It is suggested that collecting different quantitative measurements increases the utility of D-OCT and makes the method less observer-dependent.

Dynamic optical coherence tomography of skin blood vessels - proposed terminology and practical guidelines.

BACKGROUND: Dynamic optical coherence tomography (D-OCT) has recently been introduced in dermatology. In contrast to 'Standard' OCT imaging, which exclusively relies on the morphological analysis of the tissue, D-OCT allows the in vivo visualization of blood flow. Preliminary D-OCT data showed differences in the vascularization of nevus to melanoma transition, suggesting that this technology may help to differentiate between benign and malignant lesions. OBJECTIVE: Several factors may influence the quality of D-OCT imaging. Therefore, standard operating procedures as well as a common terminology are required for better validation and comparison of the images. METHODS: Here, we present practical guidelines for optimal image acquisition and a proposed terminology on vascular patterns observed by D-OCT. RESULTS: Dynamic OCT allows the morphologic distinction of different vascular shapes (e.g. dots, blobs, curves, lines), their distribution and organization within skin lesions. CONCLUSION: D-OCT adds functional information on skin microvasculature and the vascular networks within lesions.

In vivo microvascular imaging of cutaneous actinic keratosis, Bowen's disease and squamous cell carcinoma using dynamic optical coherence tomography.

BACKGROUND: A clear distinction between actinic keratosis (AK), Bowen's disease (BD) and squamous cell carcinoma (SCC) cannot reliably be made by clinical and dermoscopic evaluation alone. Dynamic optical coherence tomography (D-OCT) is a novel angiographic variant of OCT that allows for non-invasive, in vivo evaluation of the cutaneous microvascular morphology. OBJECTIVE: To investigate the microvascular structures of AK, BD and invasive SCC using D-OCT in order to gain insights into the microvascular morphology of lesions in the spectrum of keratinocyte skin cancers. METHODS: Forty-seven patients with a total of 54 lesions (18 AK, 12 BD and 24 SCC) were included in the study. D-OCT still images of AK, BD and SCC at three predefined skin depths were prepared and randomized, creating a study set of 162 D-OCT images. Three observers performed blinded evaluations of the randomized study set assessing multiple parameters including the different types of vascular morphology. Non-blinded quantitative measurements of vascular diameter were also performed. RESULTS: The blinded observer analysis suggests that D-OCT evaluation of the vascular morphology may aid in distinguishing AK, BD and SCC lesions. We identified two vascular shapes that presented significantly differently across the lesion types, namely 'blobs' and 'curves'. A strong presence of blobs at 300 µm skin depth was characteristically seen in a third of BD cases, while not or only slightly present in AK and SCC lesions. Vascular curves were predominantly present in AK lesions. CONCLUSION: We identified various vascular D-OCT features that may aid in non-invasively differentiating subtypes within the keratinocyte skin cancer spectrum.

Optical coherence tomography in the diagnosis of actinic keratosis-A systematic review.

BACKGROUND: Optical coherence tomography (OCT) is a real-time non-invasive imaging tool, introduced in dermatology in the late 1990s. OCT uses near-infrared light impulses to produce images which can be displayed in cross-sectional and en-face mode. The technique has been used to image skin diseases especially non-melanoma skin cancer including actinic keratosis (AK). Morphological characteristics of AK can be visualized in OCT images and can be used for diagnosis as well as disease monitoring. METHODS: A systematic review of original papers on AK and OCT was performed on 31.03.16 and 24.10.16 in the major databases Pubmed, MEDLINE, EMBASE, Cochrane and Svemed. Through database search and other sources, we identified 1366 titles of which 21 studies met the inclusion criteria and were used for further investigation. RESULTS: 16/16 Conventional OCT (cross-sectional images) studies described disruption of layers consistent with absence of normal layered architecture in the skin. Thickened epidermis was found in 14/16 studies and white (hyperreflective) streaks and dots were described in 11/16 studies. In High-definition optical coherence tomography (HD-OCT) images disarranged epidermis (cross-sectional images) along with an atypical honeycomb pattern (en-face images) was found in 5/5 studies and well-demarcated dermo-epithelial junction (DEJ) (cross-sectional images) was described in 3/5 studies. CONCLUSION: Several morphological characteristics of AKs were identified using Conventional OCT and HD-OCT. It is suggested that these may be used in the diagnosis of AK. Additional validation is however required to establish consensus on the optimal diagnostic criteria.

Diagnostic accuracy of optical coherence tomography in actinic keratosis and basal cell carcinoma.

BACKGROUND: Early diagnosis of non-melanoma skin cancer (NMSC) is potentially possible using optical coherence tomography (OCT) which provides non-invasive, real-time images of skin with micrometre resolution and an imaging depth of up to 2mm. OCT technology for skin imaging has undergone significant developments, improving image quality substantially. The diagnostic accuracy of any method is influenced by continuous technological development making it necessary to regularly re-evaluate methods. OBJECTIVE: The objective of this study is to estimate the diagnostic accuracy of OCT in basal cell carcinomas (BCC) and actinic keratosis (AK) as well as differentiating these lesions from normal skin. METHODS: A study set consisting of 142 OCT images meeting selection criterea for image quality and diagnosis of AK, BCC and normal skin was presented uniformly to two groups of blinded observers: 5 dermatologists experienced in OCT-image interpretation and 5 dermatologists with no experience in OCT. During the presentation of the study set the observers filled out a standardized questionnaire regarding the OCT diagnosis. Images were captured using a commercially available OCT machine (Vivosight ®, Michelson Diagnostics, UK). RESULTS: Skilled OCT observers were able to diagnose BCC lesions with a sensitivity of 86% to 95% and a specificity of 81% to 98%. Skilled observers with at least one year of OCT-experience showed an overall higher diagnostic accuracy compared to inexperienced observers. CONCLUSIONS: The study shows an improved diagnostic accuracy of OCT in differentiating AK and BCC from healthy skin using state-of-the-art technology compared to earlier OCT technology, especially concerning BCC diagnosis.

Optical coherence tomography of basal cell carcinoma: density and signal attenuation.

BACKGROUND: Basal cell carcinoma (BCC) is the most prevalent malignancy in Caucasians. Optical coherence tomography (OCT) is a non-invasive optical imaging technology using the principle of interferometry. OCT has shown a great potential in diagnosing, monitoring, and follow-up of BCC. So far most OCT studies on the subject of BCC have had a qualitative focus, i.e. on morphological analysis of the OCT images. The aim of this study was to explore the use of quantitative OCT measurements, density, and attenuation coefficient in BCC lesions as a way to improve the OCT evaluation of BCC. METHODS: The study was based on OCT images of 58 histologically verified BCC lesions and the corresponding normal adjacent skin. The study population was divided into two groups based on the OCT morphology of the BCC lesions: the "Disrupt BCC group" and the "Nodular BCC group". Density and attenuation coefficients were measured in the OCT images by specially designed software and the regions of interests (ROI) were placed directly on (ROI1) and under the visible BCC lesions (ROI2). The results were compared to the OCT images of normal adjacent skin. RESULTS: Disrupt BCC group: The densities of BCC lesions were significant lower (P = 0.002), than the normal skin in ROI1. Attenuation measurements were found to be significantly greater (P = 0.012) in BCC lesions compared to normal skin in ROI1. Nodular BCC group: Attenuation measurements were found to be significantly lower (P = 0.017) in BCC lesions compared to normal skin in ROI1. CONCLUSIONS: Our study suggests a quantitative potential of OCT in the context of BCC. This study is exploratory and requires independent verification.

Validation of Dynamic optical coherence tomography for non-invasive, in vivo microcirculation imaging of the skin.

OBJECTIVES: Dynamic optical coherence tomography (D-OCT) is an angiographic variation of OCT that non-invasively provides images of the in vivo microvasculature of the skin by combining conventional OCT images with flow data. The objective of this study was to investigate and report on the D-OCT technique for imaging of the vascular networks in skin as well as to validate the method by comparing the results against already accepted blood flow measuring tools. METHODS: 35 healthy subjects were recruited for the multicentre study, consisting of three experiments set up to examine the vascular blood perfusion during different induced physiologic changes in the blood flow. In order to validate the D-OCT images against existing techniques for blood flow measuring we performed consecutive D-OCT, chromametry and laser speckle contrast imager (LSCI) measurements on identical skin sites in all of the experiments. Blinded observer evaluations were performed in order to evaluate the vascular morphology in the D-OCT images. RESULTS: The results showed a statistically significant positive correlation between the D-OCT measurements and the LCSI flux measurements (rs=0.494; 95% CI [0.357, 0.615]; p<0.001), and also the redness a* measurements were positively correlated with the D-OCT measurements (r=0.48; 95% CI [0.406, 0.55]). D-OCT was able to reliably image and identify morphologic changes in the vascular network consistent with the induced physiological changes of blood flow. CONCLUSION: This study has initiated validation of the use of D-OCT for imaging of skin blood flow. Our results showed that D-OCT was able to reliably image and identify changes in the skin vasculature consistent with the induced physiological blood flow changes. These basic findings support the use of D-OCT imaging for in vivo microcirculation imaging of the skin.

Adjunct use of optical coherence tomography increases the detection of recurrent basal cell carcinoma over clinical and dermoscopic examination alone.

BACKGROUND: Basal cell carcinoma (BCC) is a locally destructive form of skin cancer, mainly affecting Caucasians. In the last few years non-surgical treatments of BCC have become widely used and non-invasive methods for treatment monitoring and follow-up are therefore becoming increasingly warranted. The objective of this study was to investigate the utility of adjunct use of non-invasive optical coherence tomography (OCT) imaging for the detection of recurrent BCC over clinical and dermoscopic examination alone, in a real-world setting. METHODS: A total of 58 patients, previously treated with curettage and/or MAL-PDT for BCC, were included in the study. The patients were examined clinically and dermoscopically for recurrence by a dermatologist before joining the study. The included patients were then OCT scanned and if the OCT images raised suspicion of recurrent BCC the area was biopsied. RESULTS: In 6 cases the clinical examination revealed suspicions recurrent lesions and OCT correctly identified all of these (6/6). In 49 cases the follow-up examinations showed no clinical or dermoscopic signs of recurrence, but in 12.2% (6/49) of these cases the subsequent OCT examination revealed a subclinical recurrent BCC lesion. These were all confirmed by histology. In 3 cases both the clinical and the OCT diagnosis was unclear and recurrent BCC could not be ruled out, but histology showed no sign of malignancy. CONCLUSIONS: These results suggest that the adjunct use of OCT increases the detection rate of recurrent BCC over clinical/dermoscopy examination alone.

In vivo, micro-morphological vascular changes induced by topical brimonidine studied by Dynamic optical coherence tomography.

BACKGROUND: Brimonidine is a selective α2 adrenergic receptor agonist with potent vasoconstrictive activity topically used for treatment of facial flushing and erythema caused by rosacea. Direct evidence for the in vivo morphology changes in skin vessels induced by topical application of brimonidine is limited. Dynamic optical coherence tomography is a novel technology that combines conventional OCT with information on flow and thereby provides supplementary information about the microvasculature. Dynamic OCT is non-invasive and creates high-resolution in vivo images of skin to a depth of maximum 2 mm. OBJECTIVE: The objective of this study was to examine and describe micro-morphological skin vessel changes in normal skin exposed to brimonidine gel using Dynamic OCT. MATERIALS AND METHODS: A total of 35 healthy subjects from three European clinical dermatology centres were included in the study. A normal skin area on the cheek was marked and clinically photographed. Brimonidine gel 0.33% was applied on the area and chromaticity measurements; laser speckle measurements and Dynamic OCT images were acquired at baseline and 60 min after application. The images were subsequently described in detail and quantitatively analysed. RESULTS: All the measurement tools (chromaticity, laser speckle, Dynamic OCT showed highly significant (P < 0.001) quantitative differences in blood flow before and after the application of brimonidine. In 58% of the subjects the Dynamic OCT images showed notable changes in the morphology of the blood vessel network after application of brimonidine including a marked reduction in the abundance and the diameter of the blood vessels. CONCLUSION: The vascular constriction induced by topical brimonidine gel 0.33% was visualized in vivo by Dynamic OCT and confirmed by quantitative measurements and analyses. This study shows that Dynamic OCT can detect characteristic morphological changes in the vessels and may potentially aid the monitoring of treatment effects on skin vessels following topical or laser treatment.

Optical coherence tomography in dermatology.

AIM: Optical coherence tomography (OCT) was first used in skin imaging in 1997, and since then the technology has undergone significant technological development. With its high resolution and moderate penetration depth OCT fills the imaging gap between High Frequency Ultrasound and Reflectance Confocal Microscopy. Different modalities of OCT have been developed either focusing on higher image resolution or special visualization of tissue with distinct optical properties, including collagen and blood flow. The aim of this study was to describe trends in OCT research on different dermatological diseases and review the results. METHODS: Pubmed, EMBASE, Web of science, Google Scholar and Cochrane databases were searched for the terms "optical coherence tomography", "OCT" and "dermatology" including English articles on studies of human skin tissue in vivo, finding 117 studies of original research and including 64 studies based on predefined criteria and year of publication. RESULTS: In dermatology, most studies of OCT were on non-melanoma skin cancer followed by pigmented lesions, inflammatory skin diseases, nails diseases and anatomical and physiological features investigated by OCT. In non-melanoma skin cancer diagnostic OCT criteria have been proposed and recent studies have shown a high diagnostic accuracy of 87.4% and identified objective scoring criteria for diagnosing non-melanoma skin cancer. In pigmented lesions, morphological features for differentiation of benign naevi and malignant melanoma have also been suggested, though only included small samples of malignant lesions were used in most studies. Results were further limited by a high light absorption in melanin at the used wavelenghts. Studies on skin inflammation have described morphological features of different inflammatory responses such as allergic reactions, but remain at a preliminary stage. Regarding the anatomical and physiological features of the skin, OCT studies have mainly focused on measuring epidermal thickness and morphological changes in the acute response to UV-radiation. CONCLUSION: OCT research in dermatology has undergone significant developments since its first application in 1997. The rising demand for non-invasive monitoring of skin disorders and treatment outcomes emphasize the need for further advances in the field of non-invasive imaging. Combining OCT with other technical modalities that enable quantitative measurements of e.g. blood flow or light reflectance in tissue may aid the usability of OCT in a clinical setting.

A case report of differentiating staphylococcal scalded skin syndrome and toxic epidermal necrolysis by optical coherence tomography.

BACKGROUND: Staphylococcal scalded skin syndrome (SSSS) and toxic epidermal necrolysis (TEN) both present with acute onset, high morbidity and significant mortality. Rapid diagnosis is therefore of importance. The aim of this study was to investigate and compare the presentation of these diseases using optical coherence tomography (OCT). METHODS: Two male patients with bullous diseases, SSSS and TEN, respectively, were photographed digitally, examined using dermoscopy, OCT scanned and subsequently biopsied in the said order. RESULTS: The bullous skin was visualized by OCT showing two distinct images: the SSSS-patient displayed superficial hyporefletive flaccid structures with a split high in the thickened (0.51 mm vs. 0.12 mm) epidermis while the TEN-patient demonstrated a larger hyporeflective ovoid structure with a split right below the thickened epidermis (0.18 mm vs. 0.06 mm). CONCLUSION: These findings suggest that there is a potential for the application of OCT scanning in the acute phase of SSSS and TEN in order to distinguish them for a faster diagnosis and better management and treatment.

Imaging of collagen deposition disorders using optical coherence tomography.

BACKGROUND: Collagen deposition disorders such as hypertrophic scars, keloids and scleroderma can be associated with significant stigma and embarrassment. These disorders often constitute considerable impairment to quality of life, with treatment posing to be a substantial challenge. Optical coherence tomography (OCT) provides a non-invasive, easily applicable bedside optical imaging method for assessment of the skin. It is hypothesized that OCT imaging may be useful in assessing fibrosis to avoid additional biopsies that could potentially worsen the scarring. METHOD: Thirty-three patients with ordinary scars, hypertrophic scars, keloid scarring, lichen sclerosus et atrophicus and localized or systemic scleroderma were recruited for this pilot study. Affected tissue and adjacent healthy skin were scanned using OCT and digitally photographed. Density measurements were performed in ImageJ on OCT images from scleroderma patients, both systemic and morphea (10 patients), keloid patients (10 patients) and healthy skin adjacent to keloids (10 patients). RESULTS: OCT images of scarring diseases showed varying degrees of disruption to the skin architecture. OCT characteristics were identified for each lesion type. Hypertrophic scars displayed an increased vascularity and signal-rich bands correlating to excessive collagen deposition. Keloids depicted a disarray of hyper-reflective areas primarily located in the upper dermis. Additionally, the dermis displayed a heterogeneous morphology without indications of any vascular supply or lymphatic network. In contrast to keloids, scleroderma displayed a more cohesive backscattering indicating a difference in density of collagen or other dermal structures. OCT images demonstrated no significant differences between mean density measurements in OCT images of scleroderma, keloid and healthy skin (P = 0.07). CONCLUSION: The OCT imaging appears to identify different scarring mechanisms, and therefore be of potential use in the assessment of outcomes following non-invasive therapy of e.g. early or progressive lesions.

Optical coherence tomography imaging of non-melanoma skin cancer undergoing photodynamic therapy reveals subclinical residual lesions.

BACKGROUND: Photodynamic therapy with methyl aminolaevulinate (MAL-PDT) is a widely used non-invasive treatment modality for non-melanoma skin cancer (NMSC). The outcome of MAL-PDT is usually primarily evaluated clinically. Optical coherence tomography (OCT) is a non-invasive imaging technology based on interferiometry. OCT has been proven to provide high accuracy in identifying NMSC lesions and performing thickness measurements of thin tumours. OBJECTIVES: To describe the OCT morphology in in-vivo NMSC lesions during MAL-PDT treatment and to investigate the use of OCT in evaluating the response of MAL-PDT treated NMSC lesions. METHODS: A total of 18 biopsy-proven basal cell carcinomas and actinic keratoses were monitored by OCT during 2 sessions of MAL-PDT treatment. At 3-months follow-up the patients were assessed both by OCT and clinically. If the clinical and OCT evaluation came to different conclusions on recurrence of the lesion, patients were followed more closely at clinical appointments for up to one year after the PDT treatment. RESULTS: All lesions displayed at least one OCT characteristic before MAL-PDT treatment. At 3 months follow-up, recurrence was suspected clinically in 5/18 cases, with OCT in 7/18 cases. OCT correctly identified all of the partial responses also found by the clinical examinations. In both cases where recurrence was only found in OCT, this was subsequently confirmed by histology. CONCLUSIONS: Our study suggests that OCT identified 29% more recurrences than clinical examination alone. OCT can detect subclinical residual NMSC lesions after MAL-PDT treatment and may therefore be an accurate tool for early detection of residual lesional tissue.

Optical coherence tomography imaging of non-melanoma skin cancer undergoing imiquimod therapy.

PURPOSE: To explore the application of optical coherence tomography (OCT) imaging of basal cell carcinomas (BCC) and actinic keratosis (AK) before, during and after imiquimod treatment and the ability of OCT to predict treatment outcome. METHODS: The study subjects were 20 patients with biopsy-verified BCC (9) or AK (11). Patients were OCT-scanned before, after 1 and 4 weeks of imiquimod treatment and after 3 months. Lesions were identified clinically and with OCT. Thickness and morphology of the lesions were recorded at each visit. Any remaining lesions were biopsied at follow-up. RESULTS: Complete data sets were available for 16 patients (8 women and 8 men aged 52-82 years), four in-compliant patients were excluded. OCT identified all lesions. Previously suggested OCT-criteria identified 5/8 BCCs. Crusting, ulceration and active treatment significantly reduced image quality. All BCCs cleared, but at follow-up residual structures were seen clinically in 4 cases. OCT and histology both ruled out residual BCC. For AKs significant thinning occurred after 1 week of treatment (P = 0.04). Imiquimod cleared 2/8 AKs, and significantly decreased the thickness of all lesions (P = 0.02). CONCLUSIONS: OCT could identify superficial BCC and AK before treatment. Monitoring during imiquimod treatment revealed impaired image quality most likely caused by inflammation, crusting and ulceration. On follow-up, OCT showed thinning of AKs indicating effect of treatment. All treated BCCs cleared, but where residual tissue was suspected clinically this could be ruled out by OCT.