Irritation in a bottle: Glaucoma and OSD

Editor’s Note: Ophthalmology Times is pleased to announce Lekha Mukkamala, MD, and Albert S. Khouri, MD, of Rutgers-New Jersey Medical School, Newark, NJ, as the third-place winners of the 2016 Resident Writer’s Award Program, sponsored by Allergan. The Ophthalmology Times Resident Writer’s Award Program is a unique recognition opportunity designed to promote excellence in ocular surface disease education. It was created to acknowledge outstanding case identification and written presentation skills in ophthalmology residents.

Sophia Wang, MD, and Shahzad Mian, MD, of the University of Michigan Kellogg Eye Center, Ann Arbor, are the first-place winners of this year’s Resident Writer’s Award Program. Their submission-“10 tips for OSD-associated toxic epidermal necrolysis (TEN)”-can be seen at OphthalmologyTimes.com/10TipsforTEN. Alexander Nguyen, MD, and Jessica Chow, MD, of Yale University School of Medicine, New Haven, CT, are this year’s second-place winners. Their submission-“Cyclosporine for dry eye associated with anti-PD-1 therapy”-can be seen at OphthalmologyTimes.com/CyclosporineAntiPD1.

History

Our patient is a 72-year-old African American male with a history of hypertension, well-controlled diabetes and 9 years of POAG in both eyes, with the left worse than the right. Baseline vision was 20/30 and 20/40. The patient was on maximal topical therapy in both eyes with the following regimen: brimonidine TID, dorzolamide/timolol BID, and latanoprost QHS.

He previously had questionable adherence with his medications, but now reported more regular administration, as his daughter was frequently assisting. The patient presented for follow-up with a chief complaint of increasingly blurry vision and foreign body sensation in both eyes over the past 2 months.

Examination

Visual acuity was 20/50, pinhole to 20/40 OD and 20/60, pinhole to 20/50 OS. IOP was 13 and 24 mm Hg OD and OS, respectively. Anterior segment exam was significant for 2+ diffuse punctate epithelial erosions (PEE) bilaterally, and pseudophakia bilaterally. Fundus examination revealed C/D of 0.6 OD and 0.8 OS, with mild nonproliferative diabetic retinopathy bilaterally.

Visual field results showed a dense superior arcuate defect in the left eye that was reproduced from the last field 3 months ago, when progression of the defect had been noted and compliance with medication had been stressed.

After extensive discussion with the patient and family regarding the recommendation of surgery to prevent further visual field loss in the left eye and given the persistently high IOP for goal on maximal medial therapy, the patient agreed to proceed with trabeculectomy with mitomycin C (MMC) OS.

Course

The patient underwent trabeculectomy with MMC without complication OS. The postoperative course was uneventful with a low, diffuse avascular bleb maintaining pressures in the low- to mid-teens on no topical medications.

Upon follow-up 3 months after the surgery, the patient felt that foreign body sensation persisted in the right eye but was markedly improved in the left. The patient’s vision was 20/60 with no improvement with pinhole OD, and 20/25 OS. There was 2-3+ diffuse PEE OD, while OS showed a diffuse filtering bleb with trace PEE inferiorly on the cornea. IOP was 13 mm Hg in both eyes.

Fluorescein and lissamine green staining were obtained and illustrated the compromise of the corneal epithelial surface OD. The improvement in vision in the left eye was thought to be due to the resolution of OSD with elimination of the burden of topical medications. The persistent decline in right eye acuity was attributed to worsening keratopathy that occurred with continued administration, given that visual field and IOP were stable.

Therefore, in the right eye, the patient was started on cyclosporine 0.05% BID and preservative-free artificial tears QID, with brimonidine being decreased to BID.
The ocular surface healed nicely with only trace PEE inferiorly in the right eye 4 months later. The patient’s vision improved to 20/25 with complete resolution of symptoms.

Discussion

Glaucoma medications pose a significant burden on the ocular surface, specifically the corneal epithelium. The OSDI is a subjective measure of OSD symptoms that is commonly used to identify and stratify the severity of OSD.^1-3 The OSDI is based on a questionnaire addressing three main categories: ocular symptoms, vision-related function, and environmental triggers.² At baseline, our patient had an OSDI of 27, an abnormal score that indicates the significant impact of OSD on the patient’s daily activities.

A multicenter prospective study used the OSDI and found that almost half of patients on IOP-lowering medications had at least mild OSD.¹ The preservative benzalkonium chloride has long been identified as one of the culprits for inducing corneal epithelial toxicity by its detergent properties, resulting in changes such as a decrease in the quantity of goblet cells and tear secretion.^4,5

However, it is not the only factor that may result in corneal epithelial compromise with glaucoma medications as the pH, solvents, and chemical properties of the active ingredient may also play a role.

Additional investigations have shown the frequency and cumulative duration of therapy, as well as the numbers of medications determine the extent of ocular surface toxicity. An “intensity index” (in drop-years is calculated as the number of drops per week times the therapy duration in years) has been proposed to quantify the burden of topical treatment.

Prospective study

In a prospective study of 61 patients, it was found to be positively correlated with the OSDI score. Therefore, the intensity index can serve as a more accurate measure to predict the development of OSD.² Our patient’s intensity index was 363, which would indicate a high likelihood of the patient exhibiting signs of OSD.
Several therapeutic options have been shown to be efficacious in patients with glaucoma, including cyclosporine 0.05%,⁵ sodium hyaluronate^4,6 and preservative-free artificial tears (i.e. 0.3% hydroxypropyl methylcellulose/dextran).⁴

In a prospective comparative study, cyclosporine 0.05% twice daily for 6 months significantly improved the corneal sub-basal nerve fiber layer (SBNFL) density, which is important for corneal trophism and overall corneal health. Signs and symptoms of OSD were similarly improved.⁵

Sodium hyaluronate (0.18%) and preservative-free artificial tears were demonstrated to improve signs and symptoms of OSD after 1 month of use in a masked, randomized, parallel-group study of 70 patients on anti-glaucoma medications. Greater improvement in lid margin inflammation and conjunctival injection was noted in the group using sodium hyaluronate.⁴

In our patient, after the treatment as described above, the OSDI improved to a relatively low score of 6, which was much improved from the score of 27 prior to treatment. Other compounding factors, such as diabetes and lid disease (i.e., blepharitis and meibomian gland dysfunction [MGD]), can also worsen OSD.
A recent cross-sectional study of 70 patients on glaucoma medications for at least 1 year reported the presence of mild to moderate MGD in 80% of their cohort. However, OSD markers were not worse in patients with MGD compared with those without MGD. It was concluded that OSD was mostly attributed to chronic use of topical medications rather than merely MGD.⁷

OSD symptoms are also well known to affect patient adherence with medications.⁴ A higher intensity index will naturally be found in patients requiring more medical treatment, and therefore will likely be those who have more severe glaucomatous disease. Thus, it is of even greater importance to adequately treat OSD to improve adherence.

The intensity index can perhaps be used as a measure to identify patients at risk for OSD and guide initiation or modification of treatment, whether it is via using topical cyclosporine, preservative-free solutions, decreasing the glaucoma intensity index with fixed combinations, or surgery.

Conclusion

OSD is of significant concern in patients with glaucoma on multiple topical medications. In our patient, glaucoma surgery allowed the discontinuation of topical therapy in one eye while the fellow eye continued to require intense topical therapy, highlighting the deleterious effects of topical therapy on the ocular surface.

Optimal treatment of this condition with minimizing the intensity as well as with additional pharmacologic treatments for OSD can improve visual acuity and compliance and result in better outcomes both medically and regarding patient satisfaction.

Disclosures:

Lekha Mukkamala, MDE: lekha.k.mukkamala@gmail.com

Albert S. Khouri, MDE: khourias@njms.rutgers.edu

Drs. Mukkamala and Khouri reported no financial interests in the subject matter.

References:

1. Fechtner R, Godfrey D, Budenz D, et al. Prevalence of ocular surface complaints in patients with glaucoma using topical intraocular pressure-lowering medications. Cornea. 2010;29:618-621.

2. Saade CE, Lari HB, Berezina TL, et al. Topical glaucoma therapy and ocular surface disease: a prospective, controlled cohort study. Can J Ophthalmol. 2015;50:132-136.

3. Schiffman R, Christianson M, Jacobsen G, et al. Reliability and validity of the ocular surface disease index. Arch Ophthal. 2000;118:615-621.

4. Prabhasawat P, Ruangvaravate N, Tesavibul N, Thewthong M. Effect of 0.3% hydroxypropyl methylcellulose/dextran versus 0.18% sodium hyaluronate in the treatment of ocular surface disease in glaucoma patients: a Randomized, double-blind, and controlled study. J Ocul Pharmacol Ther. 2015;31:323-329.

5. Saini M, Dhiman R, Dada T, et al. Topical cyclosporine to control ocular surface disease in patients with chronic glaucoma after long-term usage of topical ocular hypotensive medications. Eye (Lond). 2015;29:808-814.

6. Liu X, Yu F-F, Zhong Y-M, et al. Therapeutic effects of sodium hyaluronate on ocular surface damage induced by benzalkonium chloride preserved anti-glaucoma medications. Chin Med J (Engl). 2015;128:2444-2449.

7. Uzunosmanoglu E, Mocan MC, Kocabeyoglu S, et al. Meibomian gland dysfunction in patients receiving long-term glaucoma medications. Cornea. 2016;35:1112-1116.