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    Meibography in clinical practice

    Meibomian gland dysfunction (MGD) is one of the most common causes of an abnormality of the tear film lipid layer and evaporative dry eye.1–5 Numerous risk factors of MGD are reported (Table 1).6 Its prevalence varies between countries from 20% to 60%, with the highest rate in Japan.6 MGD is a chronic, diffuse abnormality of the meibomian glands, commonly characterized by terminal duct obstruction and/or qualitative/quantitative changes in the glandular secretion.7 This may result in alteration of the tear film, symptoms of eye irritation, clinically apparent inflammation and ocular surface disease.7



    MGD results in stasis of meibum inside the glands, dilatation of the ductal system and loss of glandular tissue (gland dropout) (Figure 1).5 It is recommended that the diagnosis of MGD is made by assessing ocular symptoms, lid morphology, meibomian gland mass, gland expressibility, lipid layer thickness and meibography.1

    Meibography is the only clinically in vivo technique to visualize the morphology of the meibomian glands. When using this method, the structure of the meibomian glands, including the ducts and acini, can be observed.8–16 Meibography provides photographic documentation of the meibomian gland under specialized illumination techniques.17 This article is aimed to summarize recent development and investigation in meibography and its clinical relevance.

    Meibography principles

    There are two principles in meibography. One is the transillumination of the everted lid11,18,19 the other is direct illumination, named the non-contact meibography.15,20–22 In the transillumination technique, the eyelid is everted over a light source.11,13,23 The most basic version uses white light, for example from a Finoff transilluminator. This is applied to the cutaneous side of the everted eyelid and allows observation from the palpebral conjunctival surface. Tapie24 was probably first describing evaluation of meibomian glands by transilluminating lids in 1977. He also captured the meibomian glands using infrared film (IR). Jester et al. 16 adapted the biosmicroscopic and photographic techniques to improve upon Tapie's technique.16 Subsequently many other groups have used the transillumination IR techniques in meibomian gland observation.11,18,19,25


    Figure 1: Hypothesized long-term changes of meibomian glands in MGD (1. Increased viscosity of the meibomian oil; 2. Orifice plugging and duct obstruction (hyper-keratinisation); 3. Stasis and dilatation of glands; 4. Glands atrophy and dropout)
    Arita et al. 15,20–22 were the first describing noncontact meibography in 2008. In the non-contact technique, a camera and IR light source do not touch the patient during the meibography procedure.15 Their non-contact meibograph15 consists of a slit-lamp microscope equipped with an IR charge-coupled (CCD) device video camera and an IR transmitting filter15 to allow the observation of the everted lid. The light and dark contrast of the meibomian glands is opposite that of the transillumination technique in that they appear light instead of dark.


    Figure 2: The principal of the Portable Non-Contact Meibograph (PNCM)
    The potential advantage of this technique is that it is more comfortable for patients. Furthermore this system is now commercially available in some markets as additional equipment for the Topcon slit-lamp microscope (SLM; Topcon Cooperation, Tokyo, Japan). A SLM-independent and much cheaper alternative was reported in 2011.9,26 A normal IR-CCD video camera including an IR light source was shown to be a useful and SLM independent alternative for non-contact meibography. Such cameras are readily used as security or backup cameras and are really affordable. This so named Portable NonContact Meibograhy (PNCM) consisted of an IR CCD videocamera (Pixel: PAL:628(H)x582(V), ¼" CCD Sensor, 802CHA CCD; Shenzhen LYD Technology Co. Ltd, Shenzhan, China) and near focus adaptation by a +20 Dioptre lens (Figure 2).


    Figure 3: Discrimination of the OSDI by MG morphology criteria of the upper lid (UL) and lower lid (LL).32
    Later Arita et al. demonstrated the usefulness of a SLMindependent system similar to the PNCM (handheld IR camera with IR illumination) at ARVO 2012,27 hereby confirming the usefulness of the PNCM.9


    Figure 4: Computerized analyses of the area of gland loss9
    Many common ophthalmic instruments, such as topographers, Scheimpflug cameras, fundus cameras and so on, also have built-in IR cameras combined with IR light sources, for example, designed for pupillometry. We were able to demonstrate that these devices can be used in meibography, too.28,29 However, minor optical and software modifications are required.28,29


    Figure 5: Five-grade Meiboscale.32,33
    Encouraged by these experiments28–31 and the usefulness of the PNCM9,32–34 Costruzione Strumenti Oftalmici (CSO, Florence, Italy) and bon Optic VertriebsgmbH (Lübeck, Germany), launched such modified instruments combined with the Phoenix (Version 2.5) meibography software in 2011,35 followed by Oculus Optikgeräte GmbH (Wetzlar, Germany), presenting their new Keratograph 5M with meibography option in 2012.30,31

    While the Topcon SLM system allows different magnifications due the slit-lamp microscope itself, the multifunctional ophthalmic instruments as well as the Portable Non-Contact Meibograph (PNCM) provides a close-up image of the entire eyelid (~10× magnification) with the option of digital magnification of the captured image. However, because it seems to be important to analyse the relation of the meibomian glands loss to the entire eyelid higher magnifications does not seem to be essential.9,32

    Diagnostic relevance


    Figure 6: Phoenix meibography grading system (CSO / bon Optic)
    Objective analysis of meibomian gland function can be used to assess chronic blepharitis and MGD with measurable differences. Mathers et al. 36 also supported the significance of meibomian gland dysfunction on tear osmolarity and the evaporative state of the eye.

    McCann et al. 23 suggested tear physiology, evaporimetry, interferometry, meibomian gland expression and meibography to be useful as single tests in the diagnosis of MGD. However, meibography of the lower eyelid seemed to offer the greatest effectiveness as a single measure.23 Area of loss of MG (MGL) is significantly correlated to lipid layer thickness, noninvasive break-up time and dry eye symptoms.9,32

    MGD is commonly characterized by qualitative and quantitative changes in the glandular secretion.7 Consequently a decrease in lipid layer thickness is reasonably expected with increasing MGL. Because the lipid layer is an important component to stabilize the tear film37 correlation between MGL and non-invasive break-up time is reasonable. A loss of 16.9% of the upper lid MG and 28.7% of the lower lid was suggested to be the threshold of dry eye (Figure 3).32

    The area of dropped-out glands is significantly smaller in the upper lid than of the lower lid.23,32 The meibomian glands of the lower lid are significantly wider than of the upper lid, which might be due to just having less space because the number of glands is larger in the upper lid.32 The glands of the upper lid are more bent (tortuosity) than that of the lower lid, which might be a more anatomical issue than impacted due to dysfunction of these glands.32 However, Arita et al. 38 reported relations between gland tortuosity and giant papillary conjunctivitis. Independently, whether a contact lens wearer or not, all patients with repeated allergic reaction of the tarsal conjunctiva showed more bent glands than normal patients,38 while MGL is significantly higher in contact lens wearers than in non-lens wearers.22

    Clinical practice

    Meibography has been shown to be useful in the diagnosis of MGD. The simplest way to obtain meibography might be the use of white light and transillumination of the everted eyelid, observed by a slit lamp microscope. Unfortunately, this procedure is uncomfortable for the patients. In contrast noncontact meibography is a useful, quick and a patient-friendly method for obtaining information on the meibomian gland structure.9,15

    However, there is no general standard in the classification of meibomian glands. Pflugfelder et al. 39 graded gland drop out by a four grade gestalt scale. Another similar grading scale by Nichols et al. describes the meibography images using a four grade gestalt scale.19 Arita et al. 15 scored changes in meibomian glands using a four grade scale describing meibomian gland area. In later investigation they also classified gland tortuosity applying a three grade scale when analysing relations between gland tortuosity and giant papillary conjunctivitis.38 Pult and Riede-Pult26 were first describing computerized grading of meibomian gland morphology in 2011 measuring 'area of loss of meibomian glands', 'thickness of meibomian glands' and 'bend of meibomian glands'.9,26,32 Criteria were measured applying ImageJ 1.42q (Wayne Rasband, National Institute of Health, Bethesda, Maryland, USA).

    The repeatability of this computerized grading technique (Figure 4) was analysed in comparison to a four-grade meiboscale and a new five-grade meiboscale (Figure 5). Both inter- and intra-observer agreement was best in computerized grading, followed by the fivegrade meiboscale and the fourgrade meiboscale.33 Based on this investigation a computerized system, named the Phoenix meibography module (Figure 6) was developed by CSO and bon Optic with an intra-observer repeatability of ±8% [95% Confidence Interval, 100 grade scale (grade 0–100)], being three times more exact than subjective grading.33,40

    Conclusions

    Meibography has been demonstrated to give an important additional piece of information in the assessment of meibomian gland morphology, meibomian gland changes and the diagnosis of MGD. Instruments offering noncontact meibography are now on the market. One is the Topcon Slit lamp Microscope BG-4M which is equipped with an IR light and IR CCD camera, the others are the EyeTop Topographer, Sirius Scheimpflug Camera and Cobra Fundus Camera (CSO; bon Optic)34 and the Oculus Keratograph.

    The Phoenix meibography software associated with the topographer, Scheimpflug camera and fundus camera of CSO and bon Optic includes computerized grading, which might make meibography more accessible in the daily routine and image documentation. Also, a well-trained technician can capture the images, freeing the doctor to focus on the clinical assessment and treatment.

    In the past four decades there have been many techniques introduced, however, the introduction of non-contact meibography and commercialization of such instruments, including computerized classification, will advance meibography in research and clinical practice.

    References

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    33. H. Pult and B. Riede-Pult, Invest. Ophthalmol. Vis. Sci., 2012;ARVO E-Abstract 53:588.

    34. H. Pult and B.H. Riede-Pult, J. Optom., 2012;5:2–5.

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    40. H. Pult and B.H. Riede-Pult, Unpublished study, Weinheim, Germany; 2012.

    Dr Heiko Pult
    Dr Heiko Pult is an optometrist and head of Optometry and Vision Research, Weinheim, Germany. He can be connected by Tel.: +49 ...

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