severe dry eye

A Swell Remedy

These case studies illustrate how anti-inflammatory therapies are providing relief from severe dry eye.

Tracy S. Swartz, O.D., M.S., F.A.A.O., Huntsville, Ala.

Recent research indicates the inflammatory component of severe dry eye plays a significant role in both the signs and symptoms of the disease.^1,2 As a result, eyecare practitioners are increasingly adding anti-inflammatory therapies, such as topical non-steroidal anti-inflammatory drugs (NSAIDS), corticosteroids, cyclosporine, antimicrobial drugs, oral tetracycline antibiotics and omega-three fatty acids, to their severe dry eye treatment armamentariums.^3-9

Here, I present two case studies that illustrate the benefits of prescribing anti-inflammatory therapies for severe dry eye.

Blurred vision secondary to skin disease

A 53-year-old Caucasian female presented complaining of increasing blurry vision, as each day passed, intermittent ocular redness, but no ocular pain following herpes zoster ophthalmicus OS six months prior.

History: The patient's past medical history was positive for herpes zoster infection. Her current medications consisted of valcyclovir 500 mg twice a day with trifluridine ophthalmic solution q.i.d. — prescribed by her regular optometrist — to treat the viral infection, artificial tears as needed to control dry eye symptoms and topical erythromycin b.i.d. OS for prophylaxis.

Exam findings: A refraction of −6.00+2.00 × 126 revealed her best-corrected visual acuity (BCVA) as 20/25 OD; −3.75+ 1.00 × 77 enabled her to read 20/60 OS.

Confrontational visual fields, cover test and extraocular muscles were normal OU.

The patient's left pupil was minimally reactive, but no objective or subjective afferent pupillary defect was noted OS.

Her intraocular pressure (IOP) was 14 mm Hg OD and 12 mm Hg OS. Clinical signs included data loss on topography, with irregular astigmatism OS.

Slit lamp exam revealed grade 2 lissamine green conjunctival staining OD and grade 4 staining OS. The patient's inferior cornea stained significantly as well OS.

In addition, I noted severe meibomian gland loss OS with scarring and thickening of the lid margin. Attempts to express meibum failed (see figure 1, below.)

Figure 1: This patient's severe meibomian gland loss made expressing meibum impossible.

A linear, raised pseudodendrite was noted OS, which failed to absorb Rose Bengal staining. This indicated the raised pseudodendrite was most likely due to dry eye rather than active herpetic disease (see figure 2, below.)

Figure 2: A pseudodendrite is a common finding in patients who have neurotrophic dry eye.

Dilated fundus exam revealed a healthy retina and optic nerve OU.

Diagnosis: Based on the patient's clinical presentation and history, I diagnosed her as having neurotrophic dry eye, resulting from herpes zoster infection OS, and meibomian gland dysfunction (MGD) OU.

Discussion: Neurotrophic dry eye is an unfortunate complication of herpes zoster. These patients are at risk for epithelial breakdown, secondary infection and corneal ulceration and perforation.

Persistent keratopathy and early stromal melts are managed using bandage contact lenses. Steroids should be avoided when frank epithelial defects exist, as these may exacerbate the stromal melting. Systemic anti-inflammatory agents may be required to prevent the automimmune response and halt the stromal melting. I recommend comanagement with a rheumatologist to medically manage the immune system long-term.

More severe thinning or corneal perforation may require fibrin glue and keratoplasty. Partial or complete tarsorrhaphy may be needed if the exposure keratopathy is severe or other medical intervention is unsuccessful in controlling the dry eye.

This particular patient's dry eye was complicated by severe MGD. Lid evaluation is important to discern the type of dry eye, and expression of the meibomian gland should be performed at the slit lamp to assess its ease of expression, meibum quality and gland status.

One can also look for lissamine green staining of the lid margin, or “lid wiper epitheliopathy,” which indicates more severe lid disease. Specifically, lid wiper epitheliopathy results from chronic lid disease due to inflammation and resulting lid margin epithelial breakdown.

This patient's lid disease was severe with telangiectasis, gland insipation and loss, with failure to express any meibum from the glands. When glands are clogged, no expression is possible, and the lids become thickened and scarred, I recommend using both topical and oral medications to increase comfort and improve the tear film.

In addition to treating the evaporative component of dry eye, tear substitutes should be recommended with increasing frequency and viscosity, as the aqueous deficiency component of dry eye increases in severity.

When the aforementioned treatments do not solve the problem, autologous serum, or tears compounded from the patient's blood, should be used. Autologous serum contains anti-inflammatory factors that have the potential to inhibit chemical mediators found on the ocular surface, such as inhibitors of inflammatory cytokines and matrix metalloproteinase inhibitors.

Management: The treatment goals for this patient were to reduce the inflammation related to the dry eye and MGD and allow the epithelium to heal. As a result, I prescribed a topical corticosteroid q.i.d., and a topical macrolide q.d. for three weeks. The patient continued taking valcyclovir 500 mg, b.i.d., per her infectious disease doctor's orders.

The patient returned for follow-up three weeks later, reporting improved comfort, less redness and resolution of her blurry vision. The patient's BCVA, however, was limited to 20/70 OS.

Slit lamp exam revealed grade 4 superficial punctate keratitis (SPK) OS with an unchanged pseudodendrite. Since the patient said she felt subjective improvement, I chose to continue her medications unchanged for an additional three weeks.

One week later, the patient returned to the practice complaining of sudden pain upon installation of the topical macrolide OS, which she said she experienced two days prior to this appointment. Further, her vision was unchanged.

Slit lamp exam revealed a keratoepithelial defect, where the pseudodendrite was. As a result, I diagnosed her as having a neurotrophic ulcer OS, and the corticosteroid and topical macrolide were discontinued. A bandage contact lens was placed to allow the defect to heal, and a topical fluoroquinolone was added b.i.d. for prophylaxis. Further, I prescribed Vitamin C 500 mg daily to accelerate healing.

The patient returned for follow-up three days later, reporting significant improvement in comfort. For the first time, the patient pinholed to 20/25 and refracted to 20/60 OS.

Slit lamp exam revealed the epithelial defect was 80% smaller, and the SPK had greatly improved as well. Vitamin C, topical antibiotics and artificial tears hourly with the bandage lens were continued for one week.

Upon the patient's return to the practice, her vision was 20/25 OS, and she said her comfort had greatly increased. The defect had resolved. (Had the patient's defect not resolved with the bandage lens, continuation of the lens with autologous serum every two hours would have been my next treatment step. That said, this treatment often is not covered by insurance. So if the patient couldn't afford it, a second option would have been ophthalmic inserts placed into the fornix. These slowly dissolve, lubricating the ocular surface for prolonged lengths of time. A caveat: They require removal of the bandage lens, making them a less desirable option because the cornea becomes exposed.)

The patient's lids were considerably less erythematous, and meibum was expressed with moderate pressure. A topical macrolide q.d. and a corticosteroid b.i.d. were restarted, with maintenance of the bandage lens.

One month later, the patient returned to the practice with stable vision at 20/25 OS, wearing her bandage lens.

Slit lamp exam revealed moderate SPK OS, but resolution of the pseudodendrite. I determined that the bandage lens was needed long-term, with the topical macrolide q.d. and corticosteroid b.i.d. prophylactically. In addition, I added topical cyclosporine to quell the inflammation now that the condition was under control.

As a result of her chronic ocular problems related to Herpes Zoster, the patient's infectious disease specialist determined a maintenance dosage of 500 mg valcyclovir b.i.d. was needed to prevent herpes zoster recurrence.

The lens was worn for nearly a year with a BCVA of 20/25 OS as the patient weaned herself off the lens.

A total of 16 months post her initial visit, the patient maintains 20/25 OS using the topical macrolide q.d. and corticosteroid b.i.d. with regular artificial tears and wears the lens when her eye starts to feel dry. She is doing well.

Practice benefits: The initial visit was billed as a consult, with each follow-up visit billed as a 99312 office visit. This enabled me to address her medical concerns while her regular O.D. maintained her contact lens care and yearly visits.

Emergencies were handled by me rather than her regular O.D. at my request because I needed to differentiate a herpetic outbreak from a dry eye or contact-lens-related issue.

This case not only solidified my relationship with her O.D. and her family, but also enabled me to create a relationship with an infectious disease doctor who was under the impression that all I did was “prescribe glasses.”

Contact lens-induced keratitis

A 45 year-old black male contact lens wearer presented complaining of ocular pain, severe photophobia, tearing and redness OU.

History: The patient's ocular history included keratoconus, and his systemic history was remarkable only for hypertension, for which he was taking “one medication” (not identified.)

Exam findings: The patient's BCVA was reduced to 20/40 OD and 20/30 OS in the contact lenses. Preliminary testing was normal. Refraction by plano +5.25 × 160 resulted in a BCVA of 20/50 OD, and +1.25+2.50 × 005 improved the left eye to 20/40.

Slit lamp exam revealed grade 2 conjunctival hyperemia with grade 3+ SPK OU. His lids were erythematous and thickened, with frothing and insipated glands along the lower lid margins OU.

Anterior chambers were clear, and the lenses were relatively clear.

The patient's IOP was 18 mm Hg OU, and posterior segment was normal OU.

Topography revealed keratoconus (KC) OU (see figure 3a/3b below).

Figures 3a/3b: The topography in this severe dry eye patient revealed keratoconus OU.

Diagnosis: Based on the exam findings, I diagnosed this patient as having SPK, severe dry eye and KC OU.

Discussion: KC affects one in 2,000 in the general population and has been linked to increased inflammation, particularly during contact lens wear.^8-11 Topical steroids work well in acute situations related to contact lens wear, but chronic use may lead to IOP elevation. Topical cyclosporine works well to address the lower levels of inflammation.

In addition, these patients tend to be atopic, and foretelling seasonal exacerbation of allergies is important to reduce inflammation and control the ocular surface disease. Scheduling visits to prepare for seasonal problems works well to control the disease, thereby maintaining patient comfort and vision, and instilling patient compliance for continued care.

Management: This particular case illustrates the need for dry eye disease treatment in patients who have KC. Because irregular astigmatism results from KC, treatment of dry eye may improve the distortion, secondarily improving the patient's vision. Treatment of allergies and ocular surface disease may decrease eye rubbing, which has been linked to keratoconus progression.¹² As a result, I prescribed a steroid /antibiotic combination q.i.d. and a topical macrolide q.d. to reduce inflammation and address the lid disease.

In addition, I prescribed a topical NSAID b.i.d. OU to treat the photophobia and discomfort. Finally, I instructed the patient to discontinue contact lens wear, which was problematic, given he had no glasses. I, therefore, had him return to the practice quickly in the hopes that I could obtain a stable refraction and prescribe glasses.

He returned for follow-up four days later, reporting resolution of his pain and light sensitivity. He said he hadn't worn his contact lenses since his prior visit. The patient refracted to 20/30 OU.

Slit lamp exam revealed a 50% improvement in the SPK, with mild conjunctival hyperemia OU. I instructed the patient to use a topical macrolide q.d., the topical NSAID as needed for pain, and I gave him a new spectacle correction, as I needed him to remain contact lens free.

A month later, the patient returned for follow-up. At this visit, he said he was only using the topical macrolide q.d. with artificial tears “three-to-four times per day.” He said he had no pain, and that his vision had improved since the last visit. His BCVA had improved to 20/20 OU with, thankfully, only a mild change in the refraction, with significantly changed topography.

In addition, the SPK had nearly resolved with mild lissamine green stain on the conjunctiva, and the meibomian glands expressed a slightly milky secretion with little pressure. Further, no meibomian glands were clogged, and the tear film was debris free.

I instructed the patient to use eye drops q.i.d. for the dry eye and to discontinue all other medications. I requested he return in one month, so I could assess the health of his ocular surface.

Upon his return, the patient's vision had slipped slightly to 20/25 OU, and he said his eyes were severely itchy, due to his seasonal allergies. Since his main complaint was now itching, I added a topical anti-allergy medication b.i.d. and cyclosporine b.i.d. daily OU to address the low level of inflammation.

At his one-month follow-up appointment, he reported resolution of itchiness.

Slit lamp exam revealed the anti-allergy medication and cyclosporine improved his condition. As a result, I released him on cyclosporine b.i.d. indefinitely with the topical macrolide pulsed for 14 days as needed.

Finally, I strongly recommended he discontinue contact lens wear. Since his regular O.D. was not interested in recreating problems associated with his lens wear, and his cornea was such a difficult fit, he happily supported my recommendation.

Practice benefits: This patient's initial visit was also coded as a consult (99244), with follow-up visits coded as level three office visits. Topography was performed often but cannot be billed with such frequency. Although third party reimbursement varies, I've found that once every six to 12 months is typically the limit. In this patient's case, I used topography to illustrate his progress and encourage compliance to both his medications and follow-up visits. The patient has a history of contact-lens noncompliance, and although discontinuation of the lenses was challenging, he was convinced it was to his benefit.

The aforementioned case studies support recent research that indicates the inflammatory component of severe dry eye plays a significant role in both the signs and symptoms of the disease. As a result, should you encounter similar patients, you should consider prescribing anti-inflammatory medications. OM

1. Pflugfelder SC, Jones D, JiZ, et al. Altered cytokine balance in the tear fluid and conjunctivae of patients with Sjögren's syndrome keratoconjunctivitis sicca. Curr Eye Res 1999 Sep; 19(3):201-11.
2. Tsubota K, Fujihara T, Saito K, Takeuchi T. Conjunctival epithelium expression of HLA-DR in dry eye patients. Ophthalmological 1999; 213(1): 16-19.
3. Marsh P, Pflugfelder SC. Topical nonpreserved methylprednisolone therapy of keratoconjunctivitis sicca in Sjögren's syndrome. Ophthalmology 1999 Apr;106(4):811-816.
4. Sainz De La Maza Serra M, Simon Castellvi C, Kabbani O. Nonpreserved topical steroids and lacrimal punctual occlusion for severe keratoconjunctivitis sicca. Arch Soc Esp Oftalmol 2000 Nov;75(11):751-56.
5. Maskin SL, Anderson B, Chodosh J, et al. Loteprednol etabonate 0.5% (Lotemax) versus vehicle in the management of patients with KCS and at least moderate inflammation [Abstract]. Invest Ophthalmol Vis Sci 2003;44:E-Abstract 686.
6. Solomon A., Rosenblatt M., Li DQ, et al. Doxycycline inhibition of interleukin-1 in the corneal epithelium. Invest Ophthalmol Vis Sci. 2000 Aug;41(9): 2544-57.
7. Dursun D, Kim MC, Solomon A, Pflugfelder SC. Treatment of recalcitrant recurrent corneal erosions with inhibitors of matrix metalloproteinases-9, doxycy-cline and corticosteroids. Am J Ophthalmol. 2001 Jul;132(1):8-13.
8. Rosenberg ES, Asbell PA. Essential fatty acids in the treatment of dry eye. Ocul Surf. 2010 Jan;8(1):18-28.
9. Rashid S, Jin Y, Ecoiffier T, et al. Topical omega-3 and omega-6 fatty acids for treatment of dry eye. Arch Ophthalmol. 2008 Feb;126(2):219-25.
10. Ringsdorf WM Jr, Cheraskin E. Vitamin C and human wound healing. Oral Surg Oral Med Oral Pathol. 1982 Mar;53(3):231-6.
11. Sanjay S, Huang P, Lavanya R. Herpes Zoster Ophthalmicus. Curr Treat Options Neurol. 2010 Oct 12.
12. McMonnies CW. Mechanisms of rubbing-related corneal trauma in keratoconus.Cornea 2009 Jul;28(6):607-15.