When Meds Are Not Enough

Surgical considerations for chronic dry eye.

BY STEVEN L. MASKIN, MD, FACS

Dry eye has been a passion of mine since my three years of cornea and external disease fellowship in the late 1980s. Back then, I worked on establishing rabbit meibomian gland epithelial cell clonal cultures in the laboratory of Dr. Scheffer Tseng, looking at modulation of cell growth and differentiation using serum-free growth factors.^1,2 Since entering private practice in Tampa in 1991, I have focused exclusively on non-refractive cornea and dry eye issues, even authoring an award-winning consumer book on dry eye, published by Yale University Press.³ This book has been a huge help in educating and encouraging dry eye patients to partner with me in their care and optimizing outcomes.

The quest for better patient outcomes has also led to innovative new surgical solutions for chronic, refractory dry eye. Progress in ocular surface and fornix reconstruction^4-6 has broadened our therapeutic options in a variety of clinical settings. In an exciting development reported at the 2009 ARVO annual meeting, I collaborated with Rhein Medical to develop fine stainless steel probes and tubes that have successfully been used to probe the meibomian glands of patients with obstructive meibomian gland dysfunction (MGD) with immediate and dramatic improvement of symptoms.⁷ (Disclosure — this author holds a pending patent on the method and apparatus for intraductal diagnosis and treatment of meibomian gland disease.)

Along with well-known traditional interventions such as punctal occlusion for aqueous tear deficiency and a variety of lid surgeries for abnormal lid positions and lagophthalmous (tarsorrhaphy, Botox, weighted lid implants), we are now able to reverse dry eye symptoms and restore comfort in patients refractory to non-surgical therapy with greater success than ever before.

This article will briefly review considerations for surgical solutions for refractory chronic dry eye. As every patient must be individualized, this article will simply provide guidelines — some first learned in training, then further developed and improved, and others newly innovated, such as meibomian gland probing. What follows is the approach I now use, which has proved to be useful and led to great success in managing even difficult patients suffering from chronic dry eye. I hope they will be of some benefit to you and your patients.

The Approach

Of course, targeted dry eye solutions are based on a thorough diagnostic evaluation, looking for clues as to the nature and components of the surface disease from which the patient is suffering. Also important is to identify contributing factors of each disease component using both a local and systemic analysis. Briefly, one should take into account previous ophthalmic history and topical medications and other medical and surgical history, as well as oral medications, nutriceuticals and supplements, allergies, social and family history and a careful review of systems. A physical examination should be conducted, looking for clues to systemic disease associated with dry eye, from facial signs of rosacea to the arthropathy and xerostomia of the Sjögren's syndrome patient. Then the focus should turn to the ophthalmic exam, with special attention to dry eye.

Local, medically treatable ophthalmic conditions that aggravate chronic dry eye must be identified and treated to minimize impact on dry eye status. These conditions include ocular allergies, sensitivities and toxicities, infections such as anterior blepharitis conjunctivitis, and dacryocystitis as well as other inflammatory conditions, such as ocular cicatricial pemphigoid. Interestingly, bacterial conjunctivitis may be frequently misdiagnosed in the dry eye patient who may only present with irritation and mild hyperemia without the significant discharge seen in the patient with normal tear status. It is also important to look for signs of lagophthalmous and neurotrophic (fifth cranial nerve) disease, such as herpes zoster keratitis, or neuroparalytic (seventh cranial nerve) disease, such as Bell's palsy, to stabilize the patient medically as best as possible with adjunctive supportive measures, such as lubrication and moisture chambers.

After medical, nutritional and topical therapy, along with environmental control, have been optimized, we may turn to surgical solutions to target refractory chronic dry eye. The major systems amenable to surgical intervention are as follows:

► Lid and lash status⁸

► Meibomian gland status

► Aqueous tear status

► Ocular surface and fornix status

► Tear drainage system

Lid and Lash Status⁸

The proper positioning of the lids is essential to prevent exposure of or direct mechanical trauma to the ocular surface. Exposure will create dessication stress to the surface epithelium with subsequent cell breakdown seen, for example, with ectropion, retraction (post-thermal or chemical burn, actinic exposure, thyroid eye disease, ptosis repair or other trauma) and lax lids. Trauma to the ocular surface from abnormal lid positioning may cause direct tissue damage and inflammation and may be seen with entropion and floppy superior lids, which evert during sleep. Floppy lids are well known to create sterile conjunctivitis, yet they usually maintain a relatively normal position against the globe during waking hours. The surgery selected should therefore restore a normal lid contour and healthy lid/globe apposition throughout the 24-hour day/night cycle to protect the globe and allow for a good blink. An analysis of specific surgeries is beyond the scope of this article.

In addition to proper lid positioning, an adequate blink rate and full excursion are also essential to the healthy ocular surface to prevent exposure. Although forced-blink exercises may help with the compliant patient, tarsorrhaphy may be needed for resultant exposure keratitis to decrease palpebral fissure surface area and thus concentrate and thicken the tear film. The lateral tarsorrhaphy is very effective in providing protection and reducing exposure for an extended period of time without obstructing central vision, although it may restrict peripheral visual field. Other approaches include use of weighted lid implants and use of botulinum toxin. However, implants and botulinum toxin both produce a ptotic lid, which may occlude the visual axis and produce an obvious asymmetry if unilateral. Botulinum toxin, in particular, may be helpful if the patient is not a candidate for surgical tarsorrhaphy and if the desire for reduced exposure is expected to be temporary (three months).

At times, the abnormal position is limited to a portion of the lid, seen, for example, with punctal eversion. Surgery to correct this abnormality will restore a healthy tear flow and drainage to limit nasal tarsal exposure with conjunctival inflammation.

Lash status may also cause direct mechanical trauma to the ocular surface and create dry eye symptoms. Although trichiasis trauma to the cornea is usually obvious, aberrant lash growth in the outer canthal area frequently irritates the opposing lid or temporal bulbar conjunctiva, creating secondary blepharospasm with increased surface inflammation and symptoms of dryness. Many procedures have been described, including simple epilation, radiosurgical ablation, cryoepilation, argon laser ablation, electrolysis and direct excision of follicle. Although helpful as a temporary measure, epilation is not a good long-term solution, as it does not remove the follicle. With radiosurgery, each lash is treated individually, and the process is tedious. However, by delivering a high-success rate with minimal inflammation and eyelid scarring, radiosurgery remains a popular modality. Cryoepilation is usually a successful procedure. It treats sections of eyelid one at a time but creates significant inflammation and possible postoperative lid scarring, as well as depigmentation. Argon laser and electrolysis are relatively less successful, while direct follicle removal is useful when planning for a large area of eyelashes. If trichiasis is secondary to entropion, the entropion should be managed and the trichiasis re-evaluated post-operatively.

Blepharospasm may cause ocular irritation, inducing more forceful spasms. Whether treating essential or secondary blepharospasm, injection of botulinum toxin can break this vicious cycle. For secondary blepharospasm, the underlying cause may then be accurately identified and treated. One should be careful, however, that the toxin does not track toward unintended locations, possibly affecting other muscles or tissues. For example, botulinum toxin injection into the lacrimal gland is a known research model to study dry eye.⁹ Also, its excess use may weaken the orbicularis muscle with secondary exposure.

Meibomian Gland and Lipid Tear Status

There are two new procedures to address MGD, including intraductal meibomian gland probing⁷ and intense pulsed light (IPL).¹⁰

At the ARVO meeting in May 2009, I introduced intraductal meibomian gland probing. We presented the initial 25 probed patients who had MGD diagnosed by lid margin or tarsal hyperemia, lid margin telangiectasia, irregularity or thickening and meibomian gland orifice metaplasia, plus lid tenderness or other symptoms of lid-margin congestion. The meibomian glands were probed using a stainless steel 76 μm probe of 2- or 4-mm length provided by Rhein Medical. Twenty-four of 25 patients (96%) had immediate post-probing relief, while all 25 patients had relief of symptoms by four months post-procedure. Twenty (80%) patients did not need re-treatment by average follow-up of 11.2 months, while five (20%) patients had re-treatment at an average of four to six months. Findings included intraductal resistance that could be penetrated with mild additional pressure. There was, at times, a characteristic "pop," suggestive of fibrovascular tissue with immediate and dramatic relief of lid tenderness. There was also a frequent gritty sensation in the proximal duct that has been compared to probing through a Rice Krispy, which may represent passage through hyperplastic keratinized ductal epithelium.

At this time, I have probed about 200 lids in almost 100 patients. We are currently using a visual analog scale (VAS) to standardize patient symptom status pre- and post-probing. In 44 lids of 20 patients with MGD and pre-probing lid tenderness, we have seen an 80% immediate reduction in lid tenderness post-probing, while maintaining this level of improvement for two to three months at the time of this writing. We also looked at non-lid tenderness symptoms in patients with MGD. Using VAS, in 17 lids of seven patients, we saw a 43% immediate reduction in symptoms post-probing improving to 66% improvement by two to three months. These include symptoms of lid heaviness, puffiness, awareness, irritation and discomfort, gumminess and stickiness, as well as sunburn sensation under the lid, itchy and scratchy sensations under the lid, photophobia, pressure on the eye, ptosis and epiphora.

Maskin Meibomian Gland Intraductal Probe inside MG of patient with obstructive meibomian gland dysfunction.

Based on my experience, I recommend meibomian gland probing on all patients with dry eye and irritation with a component of obstructive MGD. This is the only way to ensure complete ductal patency to let the meibum flow. One analogy might be that of a 10-car pile-up on the highway. The glass and debris are cleaned up, leaving the mass of metal in place. There's not much traffic flow there. After obtaining ductal patency, the follow-up challenge is maintenance. This may be provided by currently available pharmaceuticals including Restasis, AzaSite, doxycycline or omega-3 fatty acids, as well as warm compresses, lid hygiene and massage. We are also evaluating intraductal pharmaceutical injection through intraductal tubes to treat more difficult cases. These tubes are also available from Rhein Medical.

Intense pulsed light is a relatively new technology being evaluated for MGD. With this technique, the surgeon uses an intense pulsed light to thrombose lid-margin vascularity, decreasing inflammation and congestion with reduced symptoms.¹⁰ The treatment is delivered to the lower lids; the upper lids can be treated only indirectly through maximization of exposure to the lower lids.

Aqueous Tear Status

Surgical solutions for aqueous deficiency focus on reducing tear outflow, thereby increasing tear volume and decreasing tear osmolarity through punctal occlusion. This intervention is highly effective and usually used after environmental control, drop therapy, omega-3 fatty acid supplementation and topical Restasis prove inadequate. Preferably performed after surface inflammation is brought under control, methods include placement of punctal plugs, as well as thermocautery, electrocautery, laser ablation and radiosurgery, or direct surgical closure.

Although placement of a plug is simple, reversible and often reduces symptoms, it does not always provide satisfactory results. Many complex and suffering dry eye patients I see with difficult ocular surface problems have not benefited from plugs. They may fall out prematurely, create micro-trauma to the ocular surface with nasal surface erosions, fibrose, become colonized with micro-organisms periodically seeding the ocular surface, migrate into the canalicular system and cause sterile inflammation.

My personal preference is thermocautery. I use topical anesthesia with 3.5% lidocaine gel and a low-temp cautery. One area where it is underutilized is in the non-Sjögren's aqueous tear-deficient patient where one puncta may already be occluded. Many patients have done exceedingly well with intentional partial occlusion from use of low-temp cautery. I have had many successful post-LASIK dry eye cases respond in this way. This procedure typically creates a light, superficial scar that I can easily reverse if necessary. It should be noted that partial-occlusion plugs are available as well. In contrast, some Sjögren's patients with bone-dry eyes may need to obtain complete closure of both puncta per eye. Here I use infiltrative anesthesia with 2% lidocaine and epinephrine, and I perform thermocautery after passing a high-temp cautery wire through the puncta into the canaliculus for a deep scar.

In some cases that require complete punctal occlusion, but the punctal thermocautery repeatedly recanalizes, direct punctal or canalicular ligation is another option.¹¹

Fornix And Ocular Surface Status

Optimizing ocular surface health to prevent irritation and dry eye also requires healthy fornices and intact conjunctival and limbal stem cells. In patients with cicatrizing conjunctivitis and symptomatic fornix foreshortening with symble-pharon seen with chemical and thermal burns, ocular cicatricial pemphigoid and Stevens-Johnson syndrome, amniotic membrane grafting with intraoperative use of mitomycin C has been effective in restoring healthy fornices.⁶ At times, a buccal mucous membrane graft may be useful. Systemic immunosuppressive therapy may also need to be used. For limbal stem-cell deficiency, autografts or allografts may be indicated. The details of these procedures are beyond the scope of this article.^12-14

Maskin Probe inside MGD of patient with reconstructed lid and obstructive meibomian gland dysfunction.

Superior and inferior conjunctivochalasis (CCh) is a common disorder frequently missed or underdiagnosed, the impact of which is often underestimated. Superior CCh appears to be in the family of superior limbal keratoconjunctivitis (SLK) disorders. SLK occurs when the lid is tight to the globe, creating mechanical friction trauma to the conjuntiva, as well as lid margin and wiper. Similarly, superiorly-located mechanical trauma of lid margin and lid wiper against chalasis tissue causes an irritable pinching sensation between lid and globe.¹⁵ Both disorders may inflame lid margin and tarsus, creating increased congestion and obstruction of MGs with exacerbation of MGD. Ocular surface reconstruction has been successful in reducing these symptoms.

Inferior and temporal conjunctivochalasis may alter tear flow and cause symptoms of dry eye and irritation. These symptoms may be superimposed on aqueous tear deficiency and symptoms of MGD. Once again, ocular surface reconstruction using amniotic membrane has been shown to reduce symptoms, increasing vision and reducing dependence on artificial tears.⁵

Tear Drainage System

Delayed tear clearance (DTC) is associated with ocular-surface inflammation and irritation.¹⁶ Most often, this occurs with functional nasolacrimal outflow obstruction due to allergy or lax tissues, but it may also occur with mechanical nasolacrimal obstruction or punctal/canalicular abnormality. In cases of functional obstruction, topical steroid, as well as punctal dilation and nasolacrimal irrigation, may be helpful in relieving patients of symptoms of ocular-surface inflammation. If mechanical blockage exists in the tear drainage system, then one may consider dacryocystorhinosomy or Jones tube procedure. If punctal occlusion is necessary in cases of severe aqueous tear deficiency, then we accept the iatrogenic DTC and instead have the patient irrigate his fornices with sterile non-preserved saline to remove stagnant debris, allergens, toxins and other matter.

Summary

Chronic dry eye/ocular irritation is manageable using environmental, medical and surgical approaches. I have limited the discussion here to common causes of refractory chronic dry eye seen daily in my dry eye practice and how I successfully resolve patient symptoms with established and new surgical technologies. It is most important to separate the individual component causes of the patients' constellation of symptoms and prioritize for their relative contributions to patient suffering. Then we can target each diagnosis individually and sequentially. By doing so, the patient is not over- or undertreated but appropriately treated. OM

References

1. Maskin SL, Tseng SCG. Culture of rabbit meibomian gland using collagen gel. Invest Ophthalmol Vis Sci. 1991;32:214-223.
2. Maskin SL, Tseng SCG. Clonal growth and differentiation of rabbit meibomian gland epithelium in serum-free culture. Invest Ophthalmol Vis Sci. 1992;33:205-217.
3. Maskin, SL. Reversing Dry Eye Syndrome: Practical Ways to Improve Your Comfort, Vision and Appearance. New Haven, CT: Yale University Press; 2007.
4. Meller D, Maskin SL, Pires RTF, et a;. Amniotic membrane transplantation for symptomatic conjunctivochalasis refractory to medical treatment. Cornea. 2000;19:796-803.
5. Maskin SL. Effect of ocular surface reconstruction by using amniotic membrane transplant for symptomatic conjunctivochalasis on fluorescein clearance test results. Cornea. 2008;27:644-649.
6. Tseng SC, Di Pascuale MA, Liu DT, et al. Intraoperative mitomycin C and amniotic membrane transplantation for fornix reconstruction in severe cicatricial ocular surface diseases. Ophthalmology. 2005;112:896-903.
7. Maskin SL. Intraductal meibomian gland probing relieves symptoms of obstructive meibomian gland dysfunction. Poster presented at: Annual Meeting of the Association for Research in Vision and Ophthalmology; May 3-7, 2009; Fort Lauderdale, FL.
8. Yen, MT. Surgical therapy for ocular surface disorders. In: Pflugfelder SC, Beuerman RW, Stern ME, eds. Dry Eye and Ocular Surface Disorders. New York, NY: Marcel Dekker; 2004:325-342.
9. Suwan-apichon O, Rizen M, Rangsin R, et al. Botulinum toxin B-induced mouse model of keratoconjunctivitis sicca. Invest Ophthalmol Vis Sci. 2006;47: 133-139.
10. Toyos R. Intense, pulsed light for dry eye syndrome. Cataract Refract Surg Today. 2009;Apr:71-73.
11. DeMartelaere SL, Blaydon SM, Tovilla-Canales JL, et al. A permanent and reversible procedure to block tear drainage for the treatment of dry eye. Ophthalmic Plast Reconstr Surg. 2006;22:352-355.
12. Holland EJ, Schwartz GS. The Paton Lecture: ocular surface transplantation: 10 years' experience. Cornea. 2004;23:425-431.
13. Shortt AJ, Secker GA, Rajan MS, et al. Ex vivo expansion and transplantation of limbal epithelial stem cells. Ophthalmology. 2008;115:1989-1997.
14. Inatomi T, Nakamura T, Kojyo M, et al. Ocular surface reconstruction with combination of cultivated oral mucosal epithelial transplantation and penetrating keratoplasty. Am J Ophthalmol. 2006;142:757-764.
15. DiPascuale MA, Espana EM, Kawakita T, et al. Clinical characteristics of conjunctivochalasis with or without aqueous tear deficiency. Br J Ophthalmol. 2004;88:388-392.
16. Pflugfelder S, Maskin S, Anderson B, et al. A randomized, double-masked, placebo-controlled, multicenter comparison of loteprednol etabonate ophthalmic suspension, 0.5%, and placebo for treatment of keratoconjunctivitis sicca in patients with delayed tear clearance. Am J Ophthalmol. 2004;138:444-457.

Steven Maskin, MD, FACS, is the medical director of the Dry Eye and Cornea Treatment Center in Tampa, Fla. His practice focuses exclusively on dry eye and related diseases. He developed the meibomian gland intraductal probe with Rhein Medical.