OSD: Scratching the surface

When the (ocular surface) going gets tough …

Three cases illustrate the resourcefulness OSD demands of physicians.

By Allister Gibbons, MD, and Kendall E. Donaldson, MD, MS

Ophthalmologists can successfully manage common conditions like mild dry eye, allergies and other diseases with simple therapies for most patients, most of the time. However, once in a while we encounter a patient who continues to suffer despite treatment with all available modalities. These patients, despite having sought treatment from one excellent colleague after another, complain that these physicians could not identify and therefore treat their condition adequately. They usually bring multiple family members, printed records, large notebooks with personal notes (and questions), and a bag (or two) full of ophthalmic drops, gels and homeopathic remedies. Many of these patients also are taking myriad systemic medications for concomitant systemic illnesses; these treatments also cause or exacerbate their ocular surface disease condition. Accompanying this physical entourage (and just as challenging), we can also find frustration, anxiety, anger and sometimes a loss of faith in traditional medicine.

These patients often feel they’ve been victimized by their condition and have given up their own role in the treatment process. We consider these patients — difficult to treat and often demoralized by their inability to find relief — to be our most challenging cases. What follows are a few real-life OSD challenges and how we treated them.

CASE #1: DRY EYE — SJÖGREN’S SYNDROME

The signs and symptoms

An agreeable 82-year-old patient presents to our clinic, referred by a much-esteemed local corneal specialist. The patient tells us she has had surface symptoms for as long as she can remember, and that originally OTC lubricants brought sufficient relief for her symptoms. As time went by, topical steroids, punctal plugs, hydroxypropyl cellulose ophthalmic (Lacrisert, Bausch & Lomb) and even topical cyclosporine (Restasis, Allergan) were added to address her ever-increasing symptoms.

She informs us that she is under the care of a local rheumatologist who agrees with her Sjögren syndrome diagnosis, made on the basis of her ocular and oral signs and symptoms, along with positive antibody tests. She had been on systemic hydroxychloroquine therapy, which was recently suspended, and had also tried oral cholinergic agonists (pilocarpine, Salagen, Eisai Pharmaceuticals).

The patient tells us she can no longer keep her eyes open enough to watch television, read or drive, which is quite debilitating for this otherwise healthy and independent lady. She is at the end of her rope and, by the looks of her referral letter, so too is her regular ophthalmologist.

After carefully reviewing her history and treatment, and ruling out other causes of surface symptoms (such as exposure keratopathy or conjunctival chalasis) her Schirmer’s test reveals 1-2 mm of tear production in five minutes (without anesthesia). The rest of her exam, which included the more objective diagnostic tests of tear osmolarity and MMP-9, is remarkable for extensive confluent punctate epithelial erosions (PEE) on both corneas, which stain significantly with fluorescein. Lissamine green staining reveals her conjunctiva is quite affected as well.

What do we do now?

Possible treatments that had not been explored up until this point included mainly blood-derived products and surface protection with scleral lenses. The patient expressed serious concerns about using scleral lenses on her own, due to her lack of experience and advanced age. So we started her on 20% autologous serum tears (AST), four times a day. We maintained her topical cyclosporine and non-preserved artificial tears.

After two months of treatment, she showed improvement but was still symptomatic. So we increased the dosing to 30% AST, six times times a day in both eyes. The result was significant relief from her dry eye symptoms. Even though the patient admits to still having symptoms, she can now drive and reads quite a bit — and even gets through a whole television episode without needing eyedrops. On the slit lamp exam, she still had some PEE, though they were less severe and confluent.

The take-away

Initially, we divide patients starting serum tears into “non-responders” and “responders.” We always give a full eight weeks of initial treatment because while we have found that some patients find immediate relief, others seem to take four to six of weeks to show subjective improvement. We believe that this late-responder group probably corresponds to people whose ocular surface needs to heal before they feel any improvement.

Also, we have been surprised to find on occasion a lack of correlation between subjective improvement and objective improvement. The “responder” group can be further subdivided into a complete-response group and a partial-response group. In the latter, we usually increase the concentration of serum tears by 10% every two months until we reach 40% to 50% before moving on to more aggressive therapies.

In complex surface cases, the physician must always balance the needs and realities of the patient versus his or her own expectations of a pristine ocular surface. Sometimes taking on additional therapies after the patient is subjectively comfortable will only reduce the compliance and quality of life for the patient.

CASE #2: OCULAR GRAFT VS. HOST DISEASE

The signs and symptoms

A very nice 60-year-old male patient is referred by his hematologist. He had an uneventful bone marrow transplant for acute myeloid leukemia (AML) one year ago. Seven months after the transplant, he began to have foreign body sensation in both eyes, burning accompanied by skin changes, hair loss and diarrhea. His treating oncologist diagnosed graft versus host disease (GVHD). The physician increased the systemic tacrolimus dose, and accordingly referred him to us.

The patient is on non-preserved artificial tears and had bilateral inferior punctal plugs placed by his previous eye-care professional.

The exam is remarkable for significant meibomian gland dysfunction, a very inflamed conjunctiva in the superior tarsal area and extensive confluent punctate epithelial erosions (PEE) in both corneas, which stain significantly with fluorescein. Lissamine green staining showed his conjunctiva is quite affected as well. His Schirmer’s test reveals practically no tear production at 5 minutes.

What do we do now?

In an initial phase, ocular GVHD can cause intense inflammation of the conjunctiva, which in turn can lead to scarring. It is imperative to manage this inflammation to avoid or minimize scar formation of the superior tarsal conjunctiva. We decided to add prednisolone 1% drops every three hours in both eyes, maintain non-preserved artificial tears and see him back in a week.

At the next follow-up, his inflammation had improved significantly, though scar formation was evident. Further, his surface was still affected. Foreign body sensation and blurred vision were a major cause of concern for this patient. We started him on autologous serum tears (AST) at 30%, six times a day in this case.

After two weeks, though he showed a partial subjective response, there was no improvement in the ocular surface staining scores. We placed a bandage soft contact lens, and after 1 week the patient was significantly better. We then scheduled the patient to be fit with a PROSE (prosthetic replacement of the ocular surface ecosystem, BostonSight) device.

The good news — after 8 weeks of daily wear, he was practically symptom-free and was fully functional.

The take-away

Initially, it is very important in GVHD to use steroids to decrease inflammation and scarring. The physician must address surface disease in an orderly fashion, proportional to its severity. And it is crucial to remember that tear evaporation plays a mayor role in these patients’ dry eye disease. Addressing this early in treatment can provide faster relief.

The early fitting of a PROSE device or large scleral contact lens can be life changing in these patients, though initially a bandage contact lens can serve as a bridge until a definitive fit. Just as in Stevens-Johnson patients, who can have significant lid margin keratinization, these patients can be severely dry and also have significant scarring of the upper conjunctiva that can cause a similar lid-wiper effect. A scleral lens will help physically protect the ocular surface while maintaining the surface moist in a liquid medium.

CASE #3: RHEUMATOID MELT AFTER CATARACT SURGERY

A concerned 76-year-old patient comes referred by a very accomplished local cataract surgeon. The patient informs us that she had uneventful cataract surgery 21 days ago. Approximately one week after surgery, she developed an erosion on her cornea of the operated eye (with no pain) that quickly progressed to thinning of the cornea that led to a near perforation.

All of this information was corroborated by a referral letter (soon to be followed by a concerned call from the surgeon). The surgery had been uncomplicated (the surgeon saw no wound burn and the procedure had taken no more than 5 minutes) and the patient’s vision had improved significantly initially, only to decrease when the surface issues arose approximately one week after surgery.

The postoperative treatment regimen started with moxifloxacin q.i.d., prednisolone 1% q.i.d. and an ophthalmic bromfenac solution once daily. The primary surgeon then added non-preserved artificial tears, punctal plugs, and a self-retaining amniotic membrane (ProKera, Bio-Ttissue).

On exam, her right (unaffected eye) had moderate to severe dry eye findings, including filaments and a diffuse punctate epitheliopathy (though the patient was asymptomatic); additionally, a significant nuclear sclerotic cataract was present. Her left eye had a ring epithelial defect along the inferior margin near the limbus measuring 4 mm in length, 2 mm in height, and was more than 90% thinned in the most affected area. A monofocal posterior chamber lens was present within the capsular bag.

What do we do now?

We decided that surgical placement of a slightly decentered, large diameter graft would be the best course of action. Prior to surgery, we obtained a full rheumatologic panel, including antinuclear antibodies (ANA), rheumatoid factor, RPR (rapid plasma regain), Sjogren’s antibodies, a complete blood count and a sedimentation rate. After surgery, we started the patient on 40 mg of prednisone. The rheumatologic panel only revealed a 1:40 ANA with a mixed pattern.

The patient did very well postoperatively, with no additional corneal melting. We slowly tapered her off the oral steroid. A rheumatologic consultation revealed no specific diagnosis, and we decided not to start steroid sparring therapy unless the episode reoccurred. The patient deferred cataract surgery in the other eye until vision stabilized in her grafted eye.

Regarding preparation for the other eye, we started aggressively treating her dry eye. She is on AST 30% q.i.d and punctal plugs in the lower puncta bilaterally. We will start oral prednisone on the day of surgery and follow her much more closely than a routine cataract case.

Parting pearls

Autologous serum tears and PROSE devices allow us to treat some of our more severe ocular surface disease patients. Also, the use of amniotic membranes and treatment with topical and oral steroids may be indicated in some patients, especially those with concomitant systemic diseases (See Table, page 52).

Beware the cataract patient with significant dry eye disease during the preoperative evaluation. We now know that dry eye can appear de novo in previously asymptomatic patients after cataract surgery, or it can become more significant and severe during the postoperative recovery process. Fortunately, newly available diagnostic tools such as tear osmolarity (TearLab) and MMP-9 detection (RPS) allow us to identify at-risk patients pre-operatively.

These let us advise patients of their risk in advance and potentially treat them before upcoming surgery. Also, any new epithelial defect in a postoperative patient warrants corneal specialist involvement and extremely close follow-up, as disaster could be lurking nearby. A complete systemic work-up and appropriate systemic therapy, along with potential surgical intervention, may be required in more severe cases. OM

About the Author
	Allister Gibbons, MD received his medical degree from the University of los Andes in Santiago, Chile. He then completed his ophthalmology residency at the Fundacion Oftalmologica los Andes, and an anterior segment fellowship at that same institution in 2009. He is currently doing an ocular surface fellowship at the Bascom Palmer Eye Institute in Miami.
	Kendall E. Donaldson, MD, MS is associate professor at the Bascom Palmer Eye Institute, where she specializes in cornea/external disease and cataract/refractive surgery. She is medical director of the Bascom Palmer Eye Institute in Plantation, Fla. Disclosure: Dr. Donaldson has no financial relationships to disclose.