Imaging Modalities for Dry Eye Disease
Dry Eye Disease (DED) is a type of ocular surface disease. According to the TFOS DEWS II, it is defined as a chronic multifactorial inflammatory disease characterized by a loss of tear film homeostasis and accompanied by ocular symptoms, tear film hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities. It can present alongside or mimic various lid, conjunctival or corneal disorders. Imaging techniques are useful in diagnosing DED and the correct etiology, differentiating DED from other anterior segment disorders, and screening DED in patients presenting risk factors (e.g. systemic inflammatory diseases) or requiring preoperative evaluations for refractive or cataract surgery.
Anterior segment photo documentation can be directly done in real time examination, via cameras installed or integrated in slit lamps or smartphone-based wireless devices.
Anterior segment photos can be used to document and follow over time dry eye signs or concomitant issues such as anterior blepharitis of various etiologies (e.g. staphylococcus residues or demodex mite residues), eyelashes abnormalities (e.g. poliosis, ectropion, entropion), palpebral and bulbar conjunctival redness, eyelid margin telangiectasia, eyelid margin irregularities and fluorescein-stained cornea under white or blue light. It can also be used to measure tear meniscus height, which is useful in the diagnosis and follow-up of aqueous-deficient DED. Lipid layer quality and thickness can be also assessed with a camera. The color of the lipid layer is then compared to a scale, which allows the clinician to evaluate the lipid content of the tear film. This is useful for evaporative and mixed-etiology DED. Ocular surface staining is also an important diagnostic technique, using fluorescein dye, lissamine green dye or, less frequently, Bengal pink dye. Superficial punctate keratitis, lid-wiper epitheliopathy can be diagnosed as part of DED as well as DED mimickers such as superior limbic keratitis, can be differentiated. Images of ocular surface staining can then be saved for further analysis, or more often comparison in patient follow-ups.
Bulbar, limbal and eyelid redness, as well as lid roughness, corneal staining and meibomian gland dysfunction can be graded using the Efron scale (based on the work of Nathan Efron when at the European Center for Contact Lens Research at the University of Manchester, UK).
The CCLRU scale, developed by the Cornea and Contact Lens Research Unit (University of South Wales, Sydney, Australia), grades similar markers with an added three variables for each zone: depth, type and extent of surface area staining. The area with most staining is considered to be of most clinical significance.
Video imaging, followed by computer analysis, can also be done to evaluate blinking frequency and quality. This is indicated in patients with suspicion of incomplete blinking, or abnormal blinking rate. A higher blinking rate is usually noted in DED patients, as eye irritation is higher. Moreover, high-resolution video can be used to assess lipid content of the tear film. An interferogram is generated based on system-enhanced light reflections from the tear film. It is then compared to an interferometry color scale that is validated for a lipid layer thickness.
Furthermore, Non-Invasive Tear Break-Up Time (NITBUT) is useful in the diagnosis and follow-up of lipid-deficient dry eye disease or mixed etiology dry eye disease. The patient is instructed to blink once then the device measures how many seconds it takes for the tear film to lose its stability, thus break-up. This moment happens when the first spot of dry cornea appears after a full blink. As it is non-invasive, it is representative of the patient’s everyday state. Fluorescein Tear Break-Up Time (FTBUT) involves a fluorescein dye that is added to the cornea. FTBUT follows the same protocol, as time (in seconds) is calculated until the tear film loses stability after one blink.
Meibography is the in vivo imaging of meibomian glands, which are located in the posterior part of the eyelid. Images are taken from the inferior and superior eyelids (after superior eyelid eversion performed manually by the examiner) using interferometry. To improve image quality, dynamic and adaptive transillumination are integrated. The examiner can then compare the images to the Pult’s scale for Meibomian Gland Dysfunction grading.
It is indicated to evaluate the shape, integrity and loss of meibomian glands in inferior and superior eyelids. This allows the evaluation of the meibomian gland dysfunction and dystrophy, key aspects in MGD and evaporative DED. The degree of meibomian gland loss or dysfunction or altered architecture can also direct the clinician towards the best course of treatment for patients suffering from MGD.
Anterior Segment Optical Coherence Tomography
Anterior Segment Optical Coherence Tomography (AS-OCT) uses lower-coherence interferometry to produce cross-sectional images of the anterior segment. It can be used to get a detailed image of the cornea and tear film, when adding an extension lens to the OCT apparatus. Upper and lower tear meniscus height, areas and volumes (TMH, TMA and TMV respectively) can be measured at the junction of the bulbar conjunctiva and lower eyelid. Furthermore, AS-OCT can determine corneal pachymetry and epithelial thickness mapping. Time-Domain OCT (TD-OCT) has been used initially but Spectral-Domain OCT (SD-OCT) enables a higher resolution. Swept-Source OCT (SS-OCT) allows even higher resolution, faster image acquisition and 3-dimensional imaging. SD-OCT and SS-OCT can be used to image meibomian glands, and SS-OCT can also capture meibomian glands acini and ducts.
Although corneal pachymetry and epithelial thickness maps are not diagnostic criteria for dry eye disease, studies have shown considerable differences in patients with DED as compared to healthy eyes. Tear meniscus height however is a diagnostic aspect of aqueous-deficient DED and mixed etiology DED. Meibography is a diagnostic tool for MGD causing evaporative DED.
Corneal nerves confocal laser scanning microscopy
In-vivo confocal laser scanning microscopy can be used to assess the morphology and integrity of the corneal epithelium, sub-basal nerves, stroma and endothelium. It can also assess nerve fiber density, nerve reflectivity and tortuosity, inflammatory cell density, epithelial cell (superficial, wing and basal cell), goblet cell, stromal keratocyte, endothelial cell density and morphology. Other applications include evaluating acinar unit density and diameter, nucleocytoplasmic ratio in the conjunctiva, and further morphological assessment of the meibomian glands and lacrimal gland.
Although it is not performed at a baseline DED evaluation, it can be helpful in cases of corneal neuropathic pain or neurotrophic disease to evaluate cellular density. However, meibography, more often done using interferometry, is a diagnostic tool for MGD, which causes evaporative DED.
Advanced Combined Imaging Modalities
Some imaging apparatus can capture many images in one single evaluation, such as the Oculus Keratograph 5M ®. It can capture meibography, images for bulbar redness, tear meniscus height and non-invasive tear break-up time. Another example of such devices is the Lipiview II ® (Johnson & Johnson), which has a meibography module as well as a video module analyzing tear quality (i.e. lipid layer quality as compared to a scale of lipid content) and blinking quality (i.e. incomplete blinks calculator). More recently, companies have developed apparatus that combines dry eye disease imaging with other measurements, such as axial length measurement and anterior topography. Topcon’s device, MYAH ®, encompasses all three measurements.
For certain devices, such as the Lipiview II ® , meibography is acquired using interferometry, and thus contraindicated in patients with a history of epilepsy or at risk for seizure. Furthermore, eyelid eversion must be possible to perform before image capture.
The patient must be able to correctly position themselves on the imaging apparatus and/or slit lamp head and chinrests, thus patients with physical disabilities might not be able to undergo such imaging. All of these techniques are imaging techniques, thus no risk is involved, unless the manufacturers specified so. They are safe, non-invasive and do not involve the use of ionizing radiation, hence they are not contraindicated in pregnant women. The false positive rates of these imaging modalities are generally low, therefore they cause minimal number of overdiagnosis and undue stress to patients. These imaging techniques assist clinicians in making accurate diagnosis, choosing different treatments modalities, following up patients, and educating patients on their conditions and the evolution of their diseases.
- ↑ Craig JP, Nelson JD, Azar DT, et al. TFOS DEWS II Report Executive Summary. The Ocular Surface. 2017;15(4):802-812. doi:10.1016/j.jtos.2017.08.003
- ↑ Shimizu E, Ogawa Y, Yazu H, et al. “Smart Eye Camera”: An innovative technique to evaluate tear film breakup time in a murine dry eye disease model. Lin MC, ed. PLoS ONE. 2019;14(5):e0215130. doi:10.1371/journal.pone.0215130
- ↑ Dutt S, Vadivel S, Nagarajan S, et al. A novel approach to anterior segment imaging with smartphones in the COVID-19 era. Indian J Ophthalmol. 2021;69(5):1257. doi:10.4103/ijo.IJO_3707_20
- ↑ Binotti WW, Bayraktutar B, Ozmen MC, Cox SM, Hamrah P. A Review of Imaging Biomarkers of the Ocular Surface. Eye Contact Lens. 2020;46 Suppl 2:S84-S105. doi:10.1097/ICL.0000000000000684
- ↑ Lynn L. Contact Lens Spectrum - Deciphering Corneal Staining Scales. Contact Lens Spectrum. Published April 2007. Accessed February 10, 2022. https://www.clspectrum.com/issues/2007/april-2007/deciphering-corneal-staining-scales-(1)
- ↑ LipiView® II Ocular Surface Interferometer. Johnson & Johnson Vision. Published December 2019. Accessed February 10, 2022. https://www.jnjvisionpro.ca/products/lipiview-interferometer
- ↑ Wise RJ, Sobel RK, Allen RC. Meibography: A review of techniques and technologies. Saudi Journal of Ophthalmology. 2012;26(4):349-356. doi:10.1016/j.sjopt.2012.08.007
- ↑ Pult H, Riede-Pult B. Comparison of subjective grading and objective assessment in meibography. Cont Lens Anterior Eye. 2013;36(1):22-27. doi:10.1016/j.clae.2012.10.074
- ↑ Akiyama R, Usui T, Yamagami S. Diagnosis of Dry Eye by Tear Meniscus Measurements Using Anterior Segment Swept Source Optical Coherence Tomography. Cornea. 2015;34 Suppl 11:S115-120. doi:10.1097/ICO.0000000000000583
- ↑ Mahmoud MSED, Hamid MA, Abdelkader MF. Anterior Segment Optical Coherence Tomography of Tear Film and Cornea in Systemic Lupus Erythematosus Patients. OPTH. 2021;Volume 15:3391-3399. doi:10.2147/OPTH.S323673
- ↑ Han SB, Liu YC, Mohamed-Noriega K, Tong L, Mehta JS. Objective Imaging Diagnostics for Dry Eye Disease. Journal of Ophthalmology. 2020;2020:1-11. doi:10.1155/2020/3509064
- ↑ Erdélyi B, Kraak R, Zhivov A, Guthoff R, Németh J. In vivo confocal laser scanning microscopy of the cornea in dry eye. Graefes Arch Clin Exp Ophthalmol. 2007;245(1):39-44. doi:10.1007/s00417-006-0375-6
- ↑ Matsumoto Y, Ibrahim OMA. Application of In Vivo Confocal Microscopy in Dry Eye Disease. Invest Ophthalmol Vis Sci. 2018;59(14):DES41-DES47. doi:10.1167/iovs.17-23602
- ↑ Zhao H, Chen JY, Wang YQ, Lin ZR, Wang S. In vivo Confocal Microscopy Evaluation of Meibomian Gland Dysfunction in Dry Eye Patients with Different Symptoms. Chin Med J (Engl). 2016;129(21):2617-2622. doi:10.4103/0366-6999.192782
- ↑ MYAH. MYAH from Topcon Healthcare. Accessed February 10, 2022. https://topconmyah.com/
- ↑ Corneal topography and tear film analysis in one device - OCULUS, Inc. Accessed February 10, 2022. https://www.oculus.de/us/products/topography/keratograph-5m/oculus-keratograph-5m/