Not long ago, many physicians were just as likely to dismiss dry eye complaints as a nuisance as they were to take patients seriously and provide treatment. Treatment would typically consist of over-the-counter artificial tears and be based on a diagnosis largely reliant on patients’ symptoms and complaints. A lack of understanding of the problem meant that few physicians actively looked for dry eye disease (DED) and fewer still were motivated to dig deeper into the cause of the condition to provide targeted, individualized therapy.

It’s now 2020, and the landscape of DED has altered dramatically. First, we have a better understanding of the mechanisms at work and a realization that DED is a multifactorial and, importantly, progressive disease — not a mild inconvenience for “difficult” patients. Second, we have greater availability of effective prescription treatments, myriad artificial tear choices, emerging off-label and compounded preparations and, more recently, device-based interventions to combat the condition. Third, manufacturers have developed advanced diagnostics, including point-of-care tests, to further pinpoint a specific etiology.

Armed with a working definition of DED, ways to identify it and, most importantly, treat patients’ pathology, physicians now regularly incorporate dry eye screening as part of their routine patient workup.

This review highlights the “big three” diagnostic and treatment algorithms: TFOS DEWS, CEDARS and ASCRS.

TFOS DEWS

A look at its history

The Tear Film and Ocular Surface Society (TFOS) put forth a seminal scientific work in its 2007 report of the International Dry Eye Workshop (DEWS).¹ What has become known as TFOS DEWS expanded the scope of DED and essentially offered physicians a DED roadmap. Research since has led to even bigger gains in the science (a literature search of PubMed shows the number of peer review articles on DED has more than doubled since the first DEWS report) as well as the clinical picture — and ultimately its impact on visual outcomes and quality of life.

The sequel

A decade after its landmark report, the highly anticipated TFOS DEWS II was released.² The update tackled the literature published since 2007 and defined DED as “a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles.”

From the updated definition of TFOS DEWS II, diagnostic methods and treatment types follow. The key change in the definition is the recognition that the loss of tear film homeostasis is a fundamental characteristic of DED, as well as the acknowledgment of neurosensory abnormalities as an etiologic factor (See “DEWS to DEWS II: What changed?”).

Identifying the DED subtype (aqueous deficient or evaporative) is important for classification; however, the report notes that subtypes are part of a spectrum of disease, not distinct pathophysiological entities. Still, determining the predominant underlying etiology helps direct primary treatment approaches.

Diagnostic methodology

Because signs and symptoms of DED are poorly correlated, there is no single gold-standard diagnostic marker. Tools include:

• Patient questionnaires.
• Signs; the presence of at least one abnormal homeostatic marker (decreased tear breakup time [TBUT], tear film hyperosmolarity or ocular surface staining).
• Meibomian gland features and tear meniscus assessment.
• Differential diagnosis; DED-like symptoms include conjunctivitis, blepharitis, Sjögren syndrome, infection and lid-related disease.

“The DEWS recommendations provide a useful framework for seeing patients in a general ophthalmology or optometry practice, where a considered, stepwise approach to diagnosis and treatment can be taken and when there is no urgency of impending lens-based or keratorefractive surgery, which is the situation addressed by the ASCRS subcommittee’s algorithm” [see below], says Jay S. Pepose, MD, PhD, a co-author of one of the TFOS DEWS II reports.

Management and therapy

TFOS DEWS II presents an evidence-based, multi-staged management algorithm to determine the best treatment for each patient, based on subjective and objective measurements.

• Step 1. Patient education; environmental modifications; dietary recommendations; and home treatment with lid hygiene, warm compresses and lubricating eye drops.
• Step 2. Management with prescription medications, including topical steroids, cyclosporine, leukocyte function-associated antigen-1 antagonists, secretagogues and topical or oral antibiotics. This step also includes punctal plugs and other minor in-office procedures such as meibomian gland expression and intense pulsed light.
• Step 3. Oral secretagogues, bandage or scleral contact lenses and autologous serum eyedrops.
• Step 4. Reserved for refractory DED that may require long-term topical corticosteroids, amniotic membrane grafting or surgical intervention such as permanent punctal occlusion, tarsorrhaphy and other eyelid procedures.

ASCRS CORNEA CLINICAL COMMITTEE

The presurgical patient

If TFOS DEWS II is the motherlode from which other algorithms flow, the others discussed here seek to narrow the focus for clinical ease. The ASCRS Cornea Clinical Committee wanted to hone in on the health of the ocular surface as it relates to refractive and cataract procedures. The team’s goal was to produce an algorithm physicians could use to prepare their patients for successful surgery.³

“Our algorithm is unique in that it specifically targets the presurgical patient, recognizing that an aggressive treatment approach is required to minimize the delay before surgery,” says Christopher Starr, MD, a lead architect of the ASCRS approach. “To simplify diagnostic decision-making, in the algorithm we provide a list of preoperative tests we consider essential and those we consider optional. To guide surgeons in prioritizing therapy, we categorize ocular surface disease (OSD) as visually significant (VS-OSD) and non-visually significant (NVS-OSD).”

Any OSD and DED specifically can reduce visual quality and adversely affect refractive measurements before surgeries. Plus, surgery itself can exacerbate or induce OSD, leading to worsened vision, increased symptoms and overall dissatisfaction postoperatively. In its 2018 annual survey, ASCRS found most physicians were not using modern diagnostic tests and advanced treatments.

To help close this gap, the committee’s algorithm aids physicians in efficiently diagnosing and treating VS-OSD before surgery. By treating OSD preoperatively, postoperative visual outcomes and patient satisfaction can be significantly improved.

It should be emphasized as well that if OSD is present preoperatively and not diagnosed until after the procedure, patients may blame the surgeon for causing the condition.

Diagnosis

Tools suggested by this algorithm include:

• Questionnaire. For its algorithm, the group created the “ASCRS-Modified Preoperative OSD Standardized Patient Evaluation of Eye Dryness II questionnaire” (SPEED II; with permission from Johnson & Johnson Vision), designed specifically for preoperative refractive surgery patients. To address the implications of paying out of pocket for premium technology, they adapted items from Steven Dell, MD’s Cataract and Refractive Lens Exchange Questionnaire.
• Osmolarity. Because hyperosmolarity is central to DED, ASCRS recommends point-of-care tear testing. The sensitive threshold of 308 mOsm/L differentiates between normal patients and those with mild or moderate DED. In general, mild to moderate DED is typically diagnosed at a mean osmolarity of 315 mOsm/L and severe DED at a mean value of 336 mOsm/L. An intereye difference of 8 mOsm/L or higher is also considered abnormal, and intereye variability and day-to-day variability have been shown to correlate with increasing DED severity.
• MMP-9. The enzyme matrix metalloproteinase-9 (MMP-9) plays a key role in the breakdown of the ocular surface and can be tested at the point of care. A reading is considered positive if MMP-9 is ≥40 ng/mL. Patients with inflammation will likely benefit from preoperative topical anti-inflammatory therapy.
• Clinical exam. The mnemonic “look, lift, pull, push” can be applied for the quick, focused ocular surface examination to confirm the subtype, severity and visual significance of OSD.

Treatment

The group advocates beginning at Step 2 or later of DEWS II. A combination of medical and procedural interventions based on disease subtype and severity dictate the best approach for preoperative patients. DED’s multifactorial nature necessitates an array of therapies.

• Inflammation. Anti-inflammatory treatment can be beneficial, and pulsed topical steroids may be considered in the short term. If ocular rosacea and lid margin inflammation are present, oral tetracyclines can be considered.
• Lid margin disease. Meibomian gland dysfunction and anterior blepharitis must be treated before surgery. Relieving obstruction in the meibomian glands must be part of therapy to improve DED symptoms. Blepharitis is a common cause of cataract surgery cancellation and a major risk factor for postoperative endophthalmitis, the report notes.

CEDARS

Diagnostic-based

The Cornea, External Disease and Refractive Society (CEDARS) group emphasizes a diagnostic-based approach, which may be more practical for physicians in their day-to-day practice who see a broad range of patients. The group uses the term “dysfunctional tear syndrome” throughout the document and incorporates diagnostic tools and guidelines to direct treatment tailored to the specific disease subtype(s).⁴

According to authors Mark Milner, MD, Kenneth Beckman, MD, and Jodi Luchs, MD, “We recognized that previous algorithms tended to be severity-based rather than diagnostically based. In other words, the treatment regimen did not change much based on underlying diagnosis, but rather only based on severity. Many other approaches show a treatment protocol that starts with simple things like environmental changes and artificial tears, and then moves down the line if the first steps do not work.”

“Unfortunately,” they added, “we now know that we may not wish to treat an evaporative dry eye secondary to goblet cell disease the same way we would treat aqueous-deficient DED from Sjögren syndrome, or an evaporative dry eye secondary to lid margin disease, or an evaporative case due to Bell’s palsy exposure.” Dr. Beckman was also involved in the ASCRS algorithm development.

Four categories

Dr. Milner came up with the four major dry eye categories for the CEDARS algorithm:

• Aqueous deficiency
• Evaporative disease based on goblet cell/mucin deficiency
• Blepharitis/meibomian gland deficiency
• Exposure

These categories, however, should not be considered as mutually exclusive; there is likely overlap. Physicians must also be aware of “co-conspirators,” conditions that can masquerade as dry eye, comprising a fifth category. Masqueraders include superior limbic keratoconjunctivitis, medicamentosa, Thygeson’s, mucus fishing syndrome, contact lens-related dry eye, chemical, conjunctivitis, allergy/atopy, floppy eyelids or corneal neuralgia, and they have their own treatment trees.

Treatment

For each of the categories, the group recommended treatments that should be employed in a step-wise progression. The algorithm also suggests non-traditional therapies like hormone therapy or compounded agents or even non-drug approaches for certain diagnoses.

Notably, the authors say that the need to incorporate a broader range of dry eye treatments was also a major impetus to create their algorithm. This area is sure to get more attention as the research evolves.

MATCH THE ALGORITHM TO THE PATIENT

The three algorithms are more similar than they are different, says Dr. Starr.

“TFOS DEWS II is great for the general dry eye patient, ASCRS is great for OSD in the preoperative refractive surgery patient and CEDARS is a great methodology for approaching OSD in the general population,” he says. “The take-home message for practices is to create a protocol that works for their particular office, faithfully or partially adapting one of the algorithms or bits and pieces from each.”

Dr. Starr encourages physicians to approach DED patients as OSD patients, because there is usually more going on than “just” dry eye. This is why the ASCRS algorithm “utilized osmolarity (dry eye test) and MMP-9 (DED and other causes of inflammation) as our essential OSD screening tests.”

The overarching theme of these treatment algorithms, simply put, is this: DED is a complex multifaceted and progressive condition that requires a multifactorial approach. Patients should be assigned initial treatment, followed by an evaluation period, prior to adding concomitant treatments. The stepwise, additive approach is the best way to ensure successful visual and quality-of-life outcomes in patients suffering with all types of OSD.

“The mistake that physicians often make is in thinking one treatment is a panacea,” the CEDARS group warns. “DED — like glaucoma — is a complex disease and therefore a multi-treatment disease. Patients may be taking the commercially available drugs and still need additional therapy, which is why we advocate for considering off-label and compounded treatments.” OM

REFERENCES

1. The definition and classification of dry eye disease: report of the definition and classification subcommittee of the international dry eye workshop (2007). Ocul Surf. 2007;5:75-92.
2. Jones L, Downie LE, Korb D, et al. TFOS DEWS II management and therapy report. Ocul Surf. 2017;15;3;575-628.
3. Starr CE, Gupta PK, Farid M, et al; ASCRS Cornea Clinical Committee. An algorithm for the preoperative diagnosis and treatment of ocular surface disorders. J Cataract Refract Surg. 2019;45:669-684.
4. Milner MS, Beckman KA, Luchs JI, et al. Dysfunctional tear syndrome: dry eye disease and associated tear film disorders — new strategies for diagnosis and treatment. Curr Opin Ophthalmol. 2017;27:Suppl 1:3-47.