Image-Guided Evaluation and Monitoring of Treatment Response in Patients with Ocular Surface Disease

Fig. 3.1
IVCM meibomian gland evaluation (ad). At the time of diagnosis, IVCM scans of upper lids reveal obstruction of meibomian gland ducts close to the orifices (ab), progressive intraductal obstruction along the length of the glands (c), and the presence of inflammatory cells adjacent to the duct walls (d). AS-OCT meibography of the patient’s upper lid displays enlargement of meibomian gland ducts and reduction in length (e). In the lower lid, there is an obvious obstruction near the meibomian orifices that prevents gland secretions from reaching the ocular surface (f)

What Diagnosis Do These Findings Suggest?

IVCM and AS-OCT of MGs furnish objective parameters regarding the amount of orifices and their diameter, as well as the number of MG, their length, and their width. The AS-OCT is also able to give an overview of MG distribution in the upper and lower eyelid [5]. These imaging technologies have potential to guide physicians in the management of MGD therapy . The choice between topical and systemic therapy is guided by live imaging of the glands themselves. Visualization of intraductal inflammatory cells and fibrosis are fundamental pieces of information that can be obtained from IVCM and AS-OCT. It should be noted that near-infrared imaging of the meibomian glands with devices such as LipiView™ or Keratograph 5M™ can now provide very nice images and information about the morphology of the glands (higher quality than AS-OCT images); however, they cannot provide cellular level detail about inflammatory cells which can only be provided by IVCM. In this case, the findings are an indicator for the success of intraductal meibomian gland probing as a measure to improve symptoms attributable to glandular obstruction [6].

Intraductal MG probing was performed with 1 mm and 2 mm probes for all glands, after a 2% lidocaine local injection (into the upper lid) and proparacaine eyedrops were applied. Additionally, the lids were expressed with a meibomian gland expresser. The patient tolerated the procedure well. Further treatment included systemic treatment of doxycycline 100 mg two times per day, azithromycin ophthalmic solution 1% one application at night to eyelids, prednisolone 0.12% drops twice per day, and hot compresses along with lid massage. Flaxseed oil supplement was also prescribed.

What Are Your MGD Treatment Recommendations?

Treatment of MGD can include a surgical approach, medical therapy, or a combination of both. Invasive orifice penetration and intraductal probing is a relatively new and successful application to consider when you have to manage recurrent and severe MGD caused by intraductal fibrosis. This approach yields results immediately and is effective in relieving symptoms that accompany dry eye disease. AS-OCT and IVCM can guide this approach to therapy. These instruments are able to visualize the number of atrophic glands that are not candidates for probing. Moreover, these instruments furnish information that can reveal the length of MG ducts. This data can then be used to select the appropriate length probes before the procedure. Medical treatments include systemic tetracyclines (doxycycline, minocycline) and topical macrolides (1% azithromycin) [711]. These drugs have anti-inflammatory properties, such as inhibiting microbial lipase production, reducing the activity of tissue matrix metalloproteinases (MMP), and lowering the release of pro-inflammatory-free fatty acids and diglycerides onto the lid margin [1216].

At her last follow-up, 1 year after MG probing, the patient reported a remarkable improvement in her symptoms. She does not complain anymore about excessive tearing. She has followed her treatment instructions of maintaining lid hygiene, using hot compresses, performing lid massages, and taking flaxseed oil supplement. She stopped systemic anti-inflammatory treatment after 6 months. Ophthalmic examination showed some isolated meibomian glands occluded and a marked decrease of lid hyperemia. Her conjunctiva was normal. Slit-lamp examination revealed a normal ocular surface. Schirmer’s test was 10 mm/5 min in both eyes, and a TBUT of 8 s was found in both eyes.

Her latest IVCM scans showed MG ducts were more prevalent than before treatment and did not show inflammation in the meibomian ducts (Fig. 3.2a ). IVCM results indicated that some areas of fibrosis persisted, but obstruction was significantly reduced (Fig. 3.2b ). AS-OCT of upper and lower lids revealed a change from abnormal gland morphology (Fig. 3.1e, f ) to a more normal state (Fig. 3.2c, d).


Fig. 3.2
One year after MG probing, IVCM scans of the upper lid reveal open meibomian glands, although ducts remain smaller than normal (a). Some areas of fibrosis remain in the duct walls, especially close to the orifices (b). AS-OCT at 1 year after meibomian gland probing demonstrates a clear reduction in duct width and an elongation of gland length (c). The lower lid displays recanalization of the meibomian gland ducts along the entire length of the lid, up to the previously sealed orifices (d)

Case 2

JO is a 38-year-old female referred to our center with a diagnosis of dry eye disease. She complained of light sensitivity and pain in both eyes. She was put on artificial tears for 6 months without noticing any improvement. The patient denied having any significant disease or surgery in the past. Her visual acuity was 20/20, and her near vision was J1+ in both eyes. Her meibomian glands and eyelid margin appeared normal, as did her conjunctiva. Slit-lamp examination revealed a normal ocular surface with normal tear breakup time and without a staining. Intraocular pressure and fundus examination were normal.

How Would You Proceed at This Stage?

In all patients with a significant discrepancy between symptom and ocular surface condition, it is likely that the patient’s troubles are caused by some form of corneal neuropathy . Chronic and persistent ectopic activity of injured corneal nerves can cause pain in response to both innocuous stimulation (allodynia) and noxious stimuli (hyperalgesia) [1719]. Photoallodynia is an important symptom associated with neuropathy in the cornea. If the ocular surface does not justify the light sensitivity, it is quite common to identify nerve abnormalities. Very recently, IVCM has demonstrated the ability to detect corneal subbasal nerve damage and aberrant nerve regeneration. The tests also image the formation of neuromas and neurite sprouting in patients with photoallodynia [20].

In vivo confocal microscopy was performed on this patient. The test showed nerves with severe tortuosity, nerve beading, and frequent microneuromas (Fig. 3.3a, b ). These findings led to a diagnosis of corneal neuropathy.


Fig. 3.3
Peripheral corneal neuropathy in the subbasal nerve plexus. The IVCM scans display an abnormal arrangement of subbasal plexus nerves, reduction of nerve density, the presence of neuromas, nerve beading, and nerve sprouting (a, b). IVCM scans taken 8 months after treatment reveal a less aberrant subbasal layer. Visible differences include a marked decrease of neuromas, the disappearance of sprouting, and an increase in nerve density (c, d)

What Are Your Next Diagnostic Steps?

The first thing to do after you diagnose corneal neuropathy is spend some time with your patient in order to fully explain this disorder. Most will be relieved to know that there is an explanation for their symptoms. Many of these patients have had years of frustration searching for a solution to painful symptoms and are familiar with having their complaints written off. Now, the next step is to understand if the pain is localized peripherally (peripheral sensitization) or if there is a central component (central sensitization). The best way to determine this is with the installation of proparacaine drops.

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Jan 14, 2018 | Posted by in OPHTHALMOLOGY | Comments Off on Image-Guided Evaluation and Monitoring of Treatment Response in Patients with Ocular Surface Disease
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