Advancements in Ocular Surface Disease: From Diagnosis to Management

From Diagnosis to Management

Ophthalmology · Seminar week 23 · released August 13, 2026 · includes a discussion video

The management of dry eye disease (DED) has evolved significantly, focusing beyond aqueous deficiency to include complex factors like inflammation and neurosensory components.…

Dry eye disease is no longer adequately described as insufficient tears. Modern ocular-surface practice treats it as a heterogeneous failure of tear-film and epithelial homeostasis, often driven simultaneously by meibomian gland obstruction, aqueous deficiency, inflammation, eyelid disease, exposure, toxicity, and altered somatosensory processing. Successful management therefore depends on identifying mechanisms rather than escalating empiric drops indefinitely.

Learning Objectives

1. Explain the tear-film, inflammatory, epithelial, and neurosensory mechanisms that sustain dry eye disease.
2. Apply an evidence-based diagnostic algorithm using OSDI-6, tear-film stability, osmolarity, staining, and phenotype-directed testing.
3. Diagnose Demodex blepharitis and prescribe lotilaner using an evidence-based protocol.
4. Select appropriate candidates for intense pulsed light and integrate it with comprehensive meibomian gland dysfunction management.
5. Distinguish nociceptive dry-eye symptoms from peripheral, central, and mixed neuropathic ocular pain.
6. Coordinate multidisciplinary care for autoimmune, dermatologic, exposure-related, and pain-dominant ocular-surface disease.
7. Construct a staged, measurable treatment plan for a patient with multiple overlapping disease drivers.

Introduction to Modern Dry Eye Disease Pathophysiology

%%FIG0%% TFOS DEWS III defines dry eye as a multifactorial, symptomatic disease characterized by loss of tear-film and/or ocular-surface homeostasis in which tear-film instability and hyperosmolarity, inflammation and damage, and neurosensory abnormalities are etiologic factors (PMID: 40451408). This updates, rather than overturns, the influential TFOS DEWS II framework (PMID: 28736335). The practical implication is important: a patient does not need to fit neatly into an “aqueous-deficient” or “evaporative” box, and symptom severity need not parallel staining.

Teaching Point: Think of the functional lacrimal unit as a closed control system. Corneal and conjunctival sensory nerves detect desiccation and mechanical stress; trigeminal afferents communicate with brainstem autonomic centers; parasympathetic and sympathetic efferents regulate lacrimal secretion, goblet-cell activity, meibomian function, and blinking. Disease at any point—afferent denervation after refractive surgery, autoimmune lacrimal injury, incomplete blinking, or obstructed meibomian glands—can destabilize the entire loop.

The tear film is not simply three static layers. A superficial lipid layer retards evaporation and supports optical stability, while the underlying aqueous-mucin continuum contains electrolytes, antimicrobial proteins, growth factors, and soluble mucins. Membrane-associated mucins and the epithelial glycocalyx create a wettable surface. Goblet-cell loss, epithelial metaplasia, lipid deficiency, or reduced aqueous flow can therefore produce similar breakup patterns through different mechanisms.

Hyperosmolarity is both a marker and an amplifier. Excess evaporation or reduced aqueous delivery concentrates the exposed tear film, activating epithelial mitogen-activated protein kinase and NF-κB pathways. The resulting IL-1, TNF, chemokines, and matrix metalloproteinase-9 promote barrier disruption, epithelial apoptosis, immune-cell recruitment, and loss of goblet cells. Th1- and Th17-associated responses can extend this inflammation through conjunctiva and lacrimal tissue. An irregular epithelium then destabilizes the tear film further, while increased lid-wiper friction generates additional mechanical injury. This self-reinforcing “vicious circle” explains why replacing tears without controlling inflammation or evaporation may provide only transient relief (PMID: 29055361).

Obstructive meibomian gland dysfunction is a major evaporative driver. Terminal duct hyperkeratinization and inspissated meibum obstruct outflow; stagnation alters lipid composition and raises the meibum phase-transition temperature. Bacterial lipases can generate irritating free fatty acids, while lid-margin telangiectasia and rosacea add inflammatory signaling. Glands may shorten, dilate, or disappear over time. Conversely, aqueous deficiency from Sjögren disease, age-related lacrimal dysfunction, graft-versus-host disease, medications, or sensory denervation reduces tear volume. Most patients referred to tertiary clinics have both deficiencies rather than a single mechanism.

Nuance: Meibography demonstrates structural reserve, not real-time function. A patient may have considerable dropout with modest symptoms, while another has severe obstruction and inflammation despite relatively preserved gland architecture. Similarly, Schirmer testing estimates aqueous production but cannot explain lipid failure, exposure, toxicity, or neural pain.

Neurosensory abnormalities can produce opposite phenotypes. Peripheral sensitization causes burning, photophobia, and wind allodynia; persistent afferent activity may lead to central sensitization and symptoms disproportionate to surface findings. Reduced sensation can impair reflex tearing and blinking and may progress to neurotrophic keratopathy, in which epithelial damage is greater than the discomfort reported. “Too much pain” and “too little pain” are therefore both clinically meaningful.

Framework: At each visit, identify the dominant drivers across five domains: tear-film deficiency, eyelid or blink abnormality, ocular-surface inflammation or damage, environmental or iatrogenic exposure, and neural dysfunction. Treatment should target each active domain and use separate endpoints for symptoms, tear stability, epithelial integrity, gland function, and pain.

Audience Poll: Which mechanism most often explains treatment failure in your practice: unrecognized MGD, aqueous deficiency, ongoing inflammation, exposure or toxicity, or neuropathic pain?

Diagnostic Algorithms: OSDI-6, Tear Osmolarity, and Advanced Testing

%%FIG1%% Diagnosis begins before a device touches the eye. Establish timing, laterality, triggers, visual fluctuation, contact-lens or surgical history, topical-drop burden, systemic medications, dermatologic disease, and autoimmune symptoms. Dominant itching suggests allergy; morning pain suggests recurrent erosion or nocturnal exposure; unilateral focal pain raises concern for foreign body, infection, or herpetic disease. Ask about dry mouth, dental caries, parotid swelling, inflammatory arthralgia, rash, neuropathy, and graft-versus-host disease.

MUST ACT: Reduced acuity, a corneal infiltrate, epithelial defect, stromal thinning, anterior chamber inflammation, marked unilateral injection, new conjunctival scarring, or severe pain with nausea or headache requires evaluation beyond a routine dry-eye pathway. Do not allow a prior “dry eye” label to obscure keratitis, uveitis, scleritis, angle closure, exposure, limbal stem-cell failure, or cicatrizing disease.

The OSDI-6 contains the most discriminating items from the original OSDI domains: light sensitivity, blurred vision, night driving, watching television or a similar task, wind, and low humidity. Each item is scored from 0 to 4, producing a simple 0–24 sum. The shortened instrument correlated strongly with the 12-item OSDI and showed good repeatability in its development studies (PMID: 31442595). TFOS DEWS III recommends a score of at least 4 as a positive symptom screen (PMID: 40451408).

Nuance: OSDI-6 is not a diagnosis and should not be converted casually to the original OSDI’s 0–100 scale. It can miss symptoms outside its six domains and does not distinguish allergy, exposure, neuropathic pain, or infection. Use the same validated version longitudinally, document functional limitations separately, and add a 0–10 pain score when pain is prominent.

After a positive symptom screen, perform objective testing in an order that minimizes test-induced disturbance. Obtain tear osmolarity and noninvasive breakup time before fluorescein, anesthetic, Schirmer strips, or vigorous lid manipulation. Measure corneal sensation before anesthetic. Follow with slit-lamp examination, staining, lid eversion, gland assessment, meibography when indicated, and Schirmer testing last.

The current TFOS DEWS III diagnostic framework supports dry eye when a positive OSDI-6 accompanies at least one of the following: noninvasive breakup time below 10 seconds; osmolarity of at least 308 mOsm/L in either eye or an interocular difference greater than 8 mOsm/L; more than five corneal fluorescein spots; more than nine conjunctival lissamine-green spots; or lid-margin staining at least 2 mm long and at least 25% of the lid-wiper width (PMID: 40451408). Fluorescein breakup time is an alternative when noninvasive measurement is unavailable, but instilled volume and observer technique must be standardized.

Decision Point: Interpret osmolarity as evidence of homeostatic disruption, not as an isolated verdict. A high value or marked intereye asymmetry supports disease, but a single normal measurement does not exclude fluctuating DED. Reflex tearing, recent drops, sample handling, very low tear volume, and day-to-day variability can affect results. Repeat testing when an unexpected result would materially change management.

Subclassification requires examination of the machinery producing the abnormal result. Assess tear meniscus height and Schirmer output for aqueous deficiency. Inspect blink completeness, lagophthalmos, lid laxity, conjunctivochalasis, and lid-wiper staining. Grade meibomian orifice plugging, the number of expressible glands, and secretion quality rather than recording “MGD present” without severity. Infrared meibography documents truncation and dropout and helps set expectations: a patient with preserved glands but obstructed outflow has more recoverable function than one with extensive atrophy.

Advanced testing is most valuable when it answers a defined question. Lipid-layer interferometry can support evaporative phenotyping. Point-of-care MMP-9 positivity above the assay threshold of approximately 40 ng/mL indicates inflammatory activity but is neither specific nor reliably negative in low-volume tears. Corneal topography or epithelial mapping may explain fluctuating optics or occult epithelial irregularity. Cochet-Bonnet esthesiometry and, in selected referral centers, in vivo confocal microscopy help evaluate neurotrophic or neuropathic disease. Sjögren evaluation, conjunctival biopsy, or microbiologic testing should be driven by the clinical phenotype rather than ordered indiscriminately.

Framework: Use three questions: Does the patient have symptomatic loss of homeostasis? Which objective marker confirms it? Which tear, eyelid, surface, exposure, inflammatory, or neural driver explains it? The first establishes disease, the second provides reproducibility, and the third determines treatment.

Audience Poll: Which test most often changes your treatment plan: osmolarity, meibography, staining, Schirmer testing, MMP-9, or corneal sensation?

Demodex Blepharitis Management with Lotilaner

%%FIG2%% Demodex folliculorum primarily inhabits lash follicles, whereas Demodex brevis can occupy sebaceous and meibomian glands. Colonization becomes more common with age and does not always constitute disease. Pathologic overgrowth produces mechanical irritation, epithelial debris, microbial antigen exposure, and lid-margin inflammation; it may coexist with recurrent hordeola, chalazia, rosacea, MGD, lash misdirection, and tear-film instability.

Teaching Point: Collarettes—waxy, cylindrical sleeves of keratin, lipid, and mite debris fixed around the lash base—are the most useful clinical sign. Examine the upper lashes while the patient looks down; collarettes are easily missed when only the lower lid is inspected. Lash epilation and light microscopy can document mites when the diagnosis is uncertain, but routine epilation is unnecessary when characteristic collarettes are present.

Differentiate Demodex disease from staphylococcal anterior blepharitis, which more often produces brittle scurf and crust extending along the lash shaft; seborrheic blepharitis, with greasy scale; and allergy, in which itching and papillary conjunctivitis dominate. Rosacea-associated telangiectasia and obstructive meibum may coexist and require separate treatment. Collarettes identify Demodex involvement but do not prove that every symptom is mite mediated.

Lotilaner ophthalmic solution 0.25% is a mite-selective isoxazoline that inhibits arthropod GABA-gated chloride channels, causing mite paralysis and death while showing substantial selectivity over mammalian channels. The labeled regimen is one drop in each eye twice daily, approximately 12 hours apart, for six weeks. Remove contact lenses before instillation and wait at least 15 minutes before reinsertion; separate other ophthalmic medications by at least five minutes.

MUST ACT: Confirm Demodex blepharitis before prescribing lotilaner. Nonspecific burning without collarettes, lid-margin findings, or another reason to suspect infestation should trigger a broader differential rather than empiric acaricidal therapy.

SATURN-1 randomized 421 patients to lotilaner 0.25% or vehicle twice daily for 43 days. At day 43, complete collarette cure—zero to two collarettes on the analyzed upper lid—occurred in 44.0% versus 7.4%; clinically meaningful reduction to ten or fewer collarettes occurred in 81.3% versus 23.0%; and mite eradication occurred in 67.9% versus 17.6% (PMID: 35965392). SATURN-2 enrolled 412 patients and reproduced the effect: complete collarette cure occurred in 56.0% versus 12.5%, mite eradication in 51.8% versus 14.6%, and erythema cure in 31.1% versus 9.0% (PMID: 37285925). These are strong vehicle-controlled results, but “collarette cure,” “mite eradication,” and “symptom resolution” are distinct endpoints.

The most frequent adverse effect is transient instillation-site stinging or burning, reported in approximately 10% of treated patients. Chalazion, hordeolum, and punctate keratitis were uncommon in pivotal studies. Reassess the lid margin near the end of therapy and document collarette burden, erythema, gland obstruction, and the patient’s dominant symptoms. Persistent burning after collarettes resolve should prompt evaluation for MGD, inflammation, exposure, allergy, toxicity, or neuropathic pain rather than automatic retreatment.

Nuance: Tea-tree-oil or terpinen-4-ol preparations have variable concentrations, uncertain eradication rates, and meaningful potential for irritation or contact dermatitis. High-concentration homemade applications near the eye are unsafe. Hypochlorous-acid lid products may reduce bacterial burden and support hygiene, but they should not be represented as proven mite-eradicating substitutes for lotilaner.

Practical adjuncts include replacing contaminated eye cosmetics, avoiding shared cosmetics, cleaning reusable lid products, and treating coexisting rosacea and obstructive MGD. Routine treatment of asymptomatic household contacts is not established. Reinfestation can occur, and the optimal evidence-based retreatment interval remains uncertain; retreat when recurrent clinical disease is documented rather than maintaining indefinite acaricide exposure.

Decision Point: If collarettes improve but meibum remains thick and poorly expressible, the Demodex component has responded while MGD remains active. Move to gland-directed treatment instead of declaring lotilaner failure.

Audience Poll: After a successful six-week lotilaner course, which finding most often persists in your patients: erythema, obstructive MGD, symptoms without signs, or recurrent collarettes?

Application of Intense Pulsed Light and Meibomian Gland Dysfunction Treatment

%%FIG3%% Intense pulsed light is broad-spectrum, nonlaser energy therapy—not a generic treatment for every form of dry eye. Its best-supported role is as an adjunct for obstructive MGD, particularly when poor expressibility, abnormal meibum, short breakup time, and lid-margin telangiectasia or rosacea persist despite consistent foundational care.

Before considering a procedure, confirm that functioning gland tissue remains. Document orifice capping, meibum quality, the number of expressible glands, blink completeness, tear-film breakup, staining, and meibography. Extensive dropout predicts limited secretory recovery: IPL may improve output from surviving glands but has not been shown to regenerate atrophied glands.

Framework: Begin with preservative-free lubrication, deliberate complete blinking during screen use, and controlled lid warming. A practical home protocol is 5–10 minutes of sustained heat once or twice daily, followed by gentle massage toward the lid margin; a compress that cools after one minute is unlikely to liquefy altered meibum. Treat Demodex, allergy, exposure, and inflammatory DED concurrently. In-office options include expression, thermal pulsation, and selected light-based treatments, each with different evidence and cost.

Proposed IPL mechanisms include selective photothermolysis of superficial telangiectatic vessels, reduced inflammatory-mediator delivery, heating and liquefaction of abnormal meibum, and possible photobiomodulatory or antimicrobial effects. These mechanisms are plausible but not equally proven. The foundational paired-eye trial treated one eye of 28 participants on days 1, 15, and 45; treated eyes demonstrated improved lipid-layer grade and longer noninvasive breakup time (PMID: 25678687).

A multicenter trial comparing IPL plus meibomian gland expression with warm compress plus expression found a greater breakup-time improvement with the IPL combination (PMID: 32452923). A later double-masked trial randomized 88 patients with moderate-to-severe MGD to four sessions, two weeks apart, of IPL plus expression or sham IPL plus expression. Breakup time and gland-secretion measures favored IPL, although OSDI and meibography did not differ significantly between groups (PMID: 35737696). Meta-analyses generally support improvement in symptoms, breakup time, and gland function, but trial size, sham design, device parameters, and follow-up vary substantially (PMID: 36595759).

Nuance: Statistical improvement in breakup time does not guarantee meaningful relief for every patient. Outcomes are less predictable when pain is centrally sensitized, aqueous deficiency is profound, exposure is uncorrected, or few viable glands remain. IPL should be presented as a course with defined endpoints, not as guaranteed gland restoration.

A commonly studied schedule is three or four sessions separated by two to four weeks, usually followed by controlled gland expression. Filter, pulse structure, skin cooling, number of passes, and fluence must follow the specific device’s labeling and the patient’s Fitzpatrick type; settings from one platform should not be copied to another. Reassess symptoms, breakup time, secretion quality, expressibility, and staining approximately four weeks after the initial course. Maintenance intervals are not standardized and should be based on documented relapse.

MUST ACT: Screen for recent tanning, photosensitizing medications, active infection, suspicious or malignant skin lesions, pigment or tattoos in the treatment field, prior adverse light reactions, and skin types outside the device’s authorization. Pregnancy is generally deferred because safety data are inadequate. Use manufacturer-specified ocular shields and treatment boundaries for every pulse. Inadequate globe protection has caused anterior uveitis, posterior synechiae, pupillary distortion, iris atrophy, and persistent photophobia (PMID: 21346668).

Expected short-lived effects include warmth, erythema, edema, and mild discomfort. Burns, hyperpigmentation or hypopigmentation, lash loss, and ocular injury should be uncommon with appropriate technique. Patients with darker skin require a device specifically authorized for their skin type and an operator experienced in pigment-related risk; lowering fluence by improvisation is not an acceptable substitute.

Other MGD therapies remain relevant. A short course of oral doxycycline—often 40 mg modified-release daily or 50–100 mg daily for selected rosacea-predominant disease—is off-label and requires counseling about gastrointestinal effects, photosensitivity, pregnancy, and esophagitis. Topical azithromycin, thermal pulsation, or manual expression may be considered according to phenotype and availability. Routine high-dose omega-3 supplementation is not strongly supported: the 535-participant DREAM trial found that 3 g/day of fish-derived omega-3 was not superior to an olive-oil comparator for moderate-to-severe DED (PMID: 29652551).

Decision Point: Choose IPL when modifiable obstruction and inflammatory lid vascularity are present. Choose tear conservation or secretagogue therapy when aqueous deficiency dominates, exposure correction when closure is incomplete, and a pain pathway when symptoms remain severe after surface recovery.

Audience Poll: Which factor most influences your IPL recommendation: telangiectasia, gland expressibility, meibography, prior treatment failure, skin type, or cost?

Neuropathic Ocular Pain: Identification and Management

%%FIG4%% Neuropathic ocular pain arises when injury or disease alters signaling within the corneal-trigeminal pathway. Corneal Aδ mechanonociceptors and polymodal or cold-sensitive C fibers project through the ophthalmic division of the trigeminal nerve. Inflammation, desiccation, herpes zoster, contact-lens trauma, or surgery can alter TRPV1, TRPM8, and voltage-gated sodium-channel activity, lowering peripheral firing thresholds. Persistent afferent traffic may sensitize trigeminal brainstem and higher-order networks so that wind, light, temperature, or normal blinking becomes painful after the original insult has improved.

Clues include burning, electric, stabbing, or pressure-like pain; photoallodynia; wind hyperalgesia; pain escalating through the day; severe functional limitation; and symptoms disproportionate to staining or tear metrics. Common contexts include LASIK or PRK, cataract or corneal surgery, Sjögren disease, chronic MGD, migraine, fibromyalgia, diabetes, small-fiber neuropathy, and postherpetic neuralgia.

MUST ACT: “Pain without stain” is a warning phenotype, not permission to skip examination. Exclude infectious keratitis, occult foreign body, recurrent erosion, herpetic disease, exposure, medication toxicity, uveitis, scleritis, angle closure, and neurotrophic epithelial disease. Dry eye and neuropathic pain frequently coexist, and reduced corneal sensation does not exclude neuropathic pain.

Framework: Quantify, localize, and phenotype. Record a 0–10 pain score, descriptors, triggers, sleep and work impairment, migraine history, facial pain, systemic neuropathic symptoms, and prior procedures. The Ocular Pain Assessment Survey or NPSI-Eye can support longitudinal assessment. Test central and peripheral corneal sensation with a cotton wisp or, preferably, a Cochet-Bonnet esthesiometer. Hyperesthesia supports sensitization, while hypoesthesia suggests nerve injury or neurotrophic risk.

For the topical anesthetic challenge, document baseline pain, instill one drop of proparacaine 0.5%, and repeat the score after approximately 90 seconds. Complete relief supports a predominantly peripheral generator; partial relief suggests mixed peripheral and central mechanisms; no relief suggests a substantial central component.

Nuance: The anesthetic challenge is a localization aid, not a definitive test. It cannot reliably distinguish ordinary nociceptive surface pain from peripheral neuropathic pain, and fluctuating symptoms or incomplete anesthesia can mislead. Chronic topical anesthetic must never be dispensed for home analgesia because repeated exposure can produce epithelial toxicity, nonhealing defects, infection, stromal melting, and perforation.

In vivo confocal microscopy may show reduced subbasal nerve density, beading, tortuosity, dendritiform-cell activation, and terminal microneuromas. These findings can support a neuropathic phenotype but are not individually diagnostic or universally standardized. Microneuromas differentiated neuropathic corneal pain from conventional DED in one small retrospective cohort, but that single-center performance should not be extrapolated as perfect sensitivity or specificity (PMID: 32663518).

Peripheral-dominant pain requires removal of ongoing nociceptive input. Stop toxic or frequently preserved drops, correct exposure, treat MGD and Demodex, and suppress active inflammation. Preservative-free lubrication and moisture protection reduce mechanical stress. A carefully monitored short topical corticosteroid course may be followed by cyclosporine or lifitegrast when inflammatory DED persists. Autologous serum tears, commonly compounded at 20% and used six to eight times daily, provide epithelial and neurotrophic factors; retrospective studies have reported improvement in photoallodynia and corneal nerve morphology (PMID: 26045233). A scleral or PROSE lens can shield the surface, although severe allodynia may make lens wear intolerable.

Decision Point: When pain persists after surface rehabilitation or the anesthetic response is incomplete, involve neurology or pain medicine and introduce one systemic neuromodulator slowly. Nortriptyline may begin at 10 mg nightly and increase by 10–25 mg every one to two weeks toward 25–50 mg nightly; selected patients require higher specialist-supervised doses. Screen for cardiac conduction disease, falls, urinary retention, cognitive effects, and anticholinergic worsening of dryness. Gabapentin may begin at 100–300 mg nightly and be titrated toward divided dosing, with renal adjustment and counseling about sedation, dizziness, edema, and respiratory risk when combined with other sedatives. Pregabalin or duloxetine are alternatives selected according to comorbidity and interaction profile.

Low-dose naltrexone is off-label and supported mainly by retrospective data. A common specialist regimen begins around 1–1.5 mg nightly and titrates toward 4.5 mg; it must not be combined with opioid agonists. A retrospective cohort reported improvement in centralized neuropathic corneal pain, but concurrent treatments and nonrandomized design limit inference (PMID: 33450415).

Teaching Point: Behavioral health, sleep treatment, migraine care, and pain rehabilitation address central amplification and disability; they do not imply that pain is imaginary. Screen patients with disabling chronic pain for depression and suicidality. Set expectations in months, track function separately from surface signs, and avoid cycling rapidly through poorly tolerated drugs.

Audience Poll: Does your current workflow distinguish peripheral, mixed, and central ocular pain before systemic treatment?

Integration of Multidisciplinary Care for Complex Cases

%%FIG5%% Complex ocular-surface disease is rarely solved by adding another bottle. The useful multidisciplinary model is phenotype-triggered: the ocular-surface clinician identifies dominant mechanisms, excludes vision-threatening disease, and assigns each systemic or functional contributor to a clinician who can change it. One clinician should remain accountable for integrating the plan.

Framework: Document tear volume, evaporation and gland function, epithelial inflammation or damage, eyelid and exposure disease, and somatosensory pain at every transition of care. Add a measurable baseline, the responsible clinician, and a follow-up interval. “Refractory dry eye” without this map may represent an unrecognized driver, poor adherence, preservative toxicity, unrealistic treatment duration, or neuropathic pain rather than failure of every therapy.

Targeted systemic history determines referral. Xerostomia, recurrent caries, parotid swelling, inflammatory arthralgia, Raynaud phenomenon, rash, neuropathy, cytopenias, or marked fatigue should prompt primary-care or rheumatology evaluation for Sjögren disease or another connective-tissue disorder. Appropriate initial studies may include anti-SSA/Ro, ANA, rheumatoid factor, CBC, metabolic testing, urinalysis, and inflammatory markers, selected according to presentation. Negative SSA does not end the evaluation when objective sicca and systemic features are compelling.

The 2016 ACR/EULAR Sjögren classification system assigns three points each for anti-SSA/Ro positivity and focal lymphocytic sialadenitis with a focus score of at least 1 focus/4 mm², and one point each for ocular staining score at least 5, Schirmer output no greater than 5 mm/5 minutes, and unstimulated salivary flow no greater than 0.1 mL/min. A score of at least 4 meets classification criteria in an appropriate patient (PMID: 27785888). These are classification criteria, not a substitute for clinical diagnosis. Rheumatology, oral medicine, or otolaryngology may coordinate salivary testing or minor salivary-gland biopsy in selected seronegative patients.

Dermatology can treat facial and ocular rosacea, seborrheic dermatitis, atopy, and periocular contact dermatitis. Endocrinology and oculoplastics are important when thyroid eye disease, lid retraction, lagophthalmos, or exposure is present. Hematology or transplant teams must participate in ocular graft-versus-host disease. Dentistry addresses caries and oral complications of Sjögren disease. A contact-lens specialist can fit fluid-reservoir scleral lenses, while a corneal specialist coordinates autologous serum, amniotic membrane, neurotrophic-keratitis treatment, or management of persistent epithelial defects.

MUST ACT: Progressive fornix shortening, symblepharon, keratinization, or unexplained cicatrizing conjunctivitis requires prompt corneal and systemic evaluation. Suspected ocular mucous membrane pemphigoid generally warrants appropriately handled conjunctival or other mucosal biopsy for direct immunofluorescence; a negative biopsy does not always exclude clinically progressive disease (PMID: 30694513).

Medication reconciliation is itself a multidisciplinary treatment. Anticholinergics, sedating antihistamines, some antidepressants, isotretinoin, diuretics, and other agents can worsen tear production or meibomian function. Preserved glaucoma drops and frequent preserved lubricants may produce toxic medicamentosa. The eye clinician should describe the suspected contribution, but the prescribing clinician must decide whether substitution or dose reduction is safe. Abruptly discontinuing psychiatric, cardiovascular, or neurologic medication is inappropriate.

Nuance: Systemic immunomodulation for Sjögren disease does not reliably replace local ocular treatment. Tear conservation, anti-inflammatory therapy, lid management, exposure control, and epithelial protection remain necessary. Punctal occlusion can benefit low-volume aqueous deficiency, but active lid disease and clinically significant surface inflammation should usually be controlled first. Temporary plugs allow a reversible trial before permanent occlusion.

Pain medicine, neurology, headache care, and behavioral health become relevant when photophobia, wind sensitivity, or burning persists despite objective surface improvement. Their involvement validates the biologic pain state and permits safer systemic prescribing. High-quality randomized evidence for neuropathic corneal pain remains limited, so treatment should be slow, measured, and coordinated (PMID: 29055360).

Decision Point: Every referral should contain a specific question: “Evaluate possible Sjögren disease,” “treat rosacea driving MGD,” “correct exposure,” “fit a scleral lens,” or “co-manage mixed peripheral and central ocular pain.” Shared documentation should also state which clinician monitors intraocular pressure, systemic adverse effects, and treatment response.

Audience Poll: Which multidisciplinary relationship most often changes your patients’ outcomes: rheumatology, dermatology, oculoplastics, scleral-lens service, or pain medicine?

Case-Based Discussion

Case of Persistently Dry Eyes: Diagnostic and Therapeutic Advances

A 58-year-old accountant presents with 18 months of bilateral burning, fluctuating vision, foreign-body sensation, and photophobia. Symptoms worsen late in the day, during computer work, and in moving air. She uses preserved redness-relief and lubricant drops six to eight times daily, with relief lasting minutes. Warm compresses have been sporadic. She reports facial flushing, dry mouth, increasing dental caries, fatigue, and morning hand stiffness. She has no contact-lens wear, recent ocular surgery, unilateral discharge, or history of herpetic keratitis.

MUST ACT: Before calling this refractory DED, exclude infection, uveitis, recurrent erosion, exposure keratopathy, toxic keratopathy, limbal failure, and cicatrizing conjunctivitis. Her corrected acuity is 20/20 in each eye, pupils and anterior chambers are normal, and there is no infiltrate, epithelial defect, stromal thinning, or conjunctival scarring.

Testing is sequenced to preserve the tear film. Her OSDI-6 is 18/24 and baseline pain is 7/10. Osmolarity is 323 mOsm/L OD and 311 mOsm/L OS; both the absolute threshold and 12-mOsm/L asymmetry support homeostatic disruption. Noninvasive breakup time is 3.8 seconds. Corneal sensation is mildly reduced bilaterally. Slit-lamp examination shows more than ten upper-lid collarettes, lid-margin telangiectasia, capped meibomian orifices, and thick, poorly expressible meibum. Meibography demonstrates approximately one-third lower-lid gland dropout. There are more than five inferior corneal fluorescein spots and an ocular staining score of 6. Schirmer testing with anesthesia measures 3 mm OD and 4 mm OS at five minutes.

Framework: This is mixed-mechanism disease: aqueous deficiency, evaporative DED from obstructive MGD and probable ocular rosacea, Demodex blepharitis, surface inflammation, and toxicity from preserved drops. The symptom–sign mismatch and mild sensory loss raise concern for neuropathic contribution, but active nociceptive drivers must first be treated. Allergy is less likely without dominant itching or papillary conjunctivitis; isolated aqueous deficiency would not explain collarettes and obstructed meibum.

The initial plan removes aggravators and treats high-confidence drivers. She stops vasoconstrictor drops and changes to preservative-free lipid-containing tears four times daily and as needed, with ointment and moisture protection overnight. She begins deliberate blink exercises, screen breaks, airflow modification, and 8–10 minutes of controlled lid warming followed by gentle massage. Confirmed Demodex blepharitis is treated with lotilaner 0.25%, one drop in each eye twice daily for six weeks.

Because infection and epithelial defect have been excluded, a monitored anti-inflammatory bridge is reasonable: loteprednol 0.5% four times daily for two weeks, then twice daily for two weeks, alongside cyclosporine 0.05% twice daily for longer-term control. Baseline intraocular pressure is documented and rechecked within two to four weeks. She is warned that cyclosporine commonly stings and may require 8–12 weeks or longer for meaningful benefit.

Decision Point: Punctal plugs are deferred. Retaining tears while Demodex, poor-quality meibum, and inflammation are active may worsen the inflammatory reservoir. If aqueous output remains low after lid and surface control, temporary plugs can test whether conservation provides additional benefit.

Her xerostomia, caries, and inflammatory symptoms prompt targeted primary-care and rheumatology assessment. Anti-SSA/Ro is positive. Combined with an ocular staining score of 6 and Schirmer results no greater than 5 mm/5 minutes, she meets ACR/EULAR classification criteria in the appropriate clinical context (PMID: 27785888). Rheumatology evaluates systemic activity while ophthalmology continues local therapy; systemic treatment does not substitute for ocular-surface management.

At six weeks, collarettes are reduced to two per upper lid and erythema has improved, but obstructive meibum and telangiectasia persist. With Fitzpatrick type II skin, viable glands on meibography, and no photosensitizing medication or other contraindication, she undergoes four device-specific IPL sessions at two-week intervals followed by controlled gland expression. At three months, breakup time improves to approximately six seconds, gland secretions are clearer, and corneal staining is minimal.

Despite objective improvement, burning and photophobia remain 6/10. A proparacaine challenge reduces pain to 3/10 but does not abolish it, suggesting a persistent peripheral generator with central sensitization. Take-home anesthetic is explicitly prohibited. The corneal service initiates autologous serum tears 20% six times daily and considers a scleral-lens trial. Pain medicine starts nortriptyline 10 mg nightly with slow titration after reviewing ECG history, anticholinergic risk, interactions, and fall risk. Symptoms, pain, function, staining, breakup time, collarettes, and gland expressibility are followed as separate endpoints.

Teaching Point: Improvement in staining does not invalidate persistent pain. The case is successful only when each residual mechanism is recognized rather than forcing every symptom into the dry-eye severity score.

Audience Poll: At the first visit, which intervention should be prioritized: lotilaner, punctal occlusion, IPL, or systemic neuromodulation?

Tonight on Shift

• [ ] Exclude infiltrate, epithelial defect, thinning, uveitis, exposure, and cicatrizing disease before labeling ocular pain as dry eye.
• [ ] Record OSDI-6 and phenotype tear stability, osmolarity, staining, aqueous output, lid disease, meibum, and corneal sensation.
• [ ] Look specifically for lash-base collarettes and confirm Demodex before prescribing lotilaner 0.25% twice daily for six weeks.
• [ ] Reserve IPL for documented, recoverable obstructive MGD and use device-specific shielding, skin-type selection, and settings.
• [ ] Suspect neuropathic pain when symptoms remain disproportionate; never dispense topical anesthetic for chronic home analgesia.
• [ ] Give every complex patient a staged plan with objective endpoints, one coordinating clinician, targeted referrals, and safety monitoring.

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