Editor's Commentary

Whenever I prescribe an off-label treatment for a patient, especially for the first time, I tend to experience several thoughts and feelings. The first is generally optimism. If I’m considering going off-label, it’s usually because standard therapies haven’t worked, and I genuinely want to help my patient. The second feeling is probably a mix of apprehension and nervousness. Venturing outside of established practice guidelines and knowing that a treatment isn’t backed by formal approval should always be a cautious space. Third, I feel an even greater sense of responsibility because my patient is trusting me to balance unknown risks with potential benefits. 

As we know, evidence-based research is the gold standard for making informed clinical decisions. By ensuring that our therapeutic interventions are supported by scientific data, we can generally reduce unnecessary medical risks while improving patient outcomes. However, our dry eye and ocular surface disease patients don’t always fit into nice, neat categories, wrapped up with a pretty bow. Challenging cases often require creativity, reliance on clinical judgment and experience, and often, the use of a treatment outside of its approved indication. While it may seem risky, off-label treatments sometimes offer the best hope for patients with complex or refractory cases where scientific evidence is sparse.

Whether we prescribe off-label therapy instead of (or in addition to) evidence-based medicine, we need to balance our professional experience, scientific knowledge base, patient wishes and overall well-being, and the responsiveness and severity of the disease we’re treating with known and unknown potential risks. Monitoring for adverse effects is always important, but it becomes even more so when we don’t know the full risk profile. Staying current with the latest scientific literature and professional standards of care is essential for clinicians to achieve the best possible outcomes for their patients.

Amber Gaume Giannoni, OD, FAAO
Editor

Clinician's Corner 

Mark Schaeffer, OD
Clinical Excellence Captain at MyEyeDr, Birmingham, AL

Documentation for Off-label Use of Medication: What You Need to Know 

Off-label prescribing, or using medications for conditions, dosages, or patient populations not formally approved by the FDA, is a common and often necessary practice in optometry. Whether prescribing topical steroids for dry eye disease or repurposing antivirals for atypical ocular infections, off-label use can be clinically beneficial. However, it also carries documentation and liability considerations. This article addresses key questions about chart documentation requirements, informed consent, and risk management, to ensure patient safety and legal protection. 

Proper records protect the patient and practitioner by: 

• Demonstrating clinical rationale
• Providing evidence of informed consent
• Aligning with standards of care

Regulatory bodies and malpractice insurers emphasize that documentation must justify the decision to deviate from labeled uses. Even if off-label use is evidence-based, incomplete records can expose clinicians to legal risks if complications arise. 

When prescribing off-label, include the following in the patient’s chart: 

1. Clinical justification
   • Clearly state the diagnosis and why the off-label medication was chosen. 
   • Include reference-supported evidence (eg, peer-reviewed studies, clinical guidelines). Example: “Patient was prescribed loteprednol 0.5% 1 gt qam off-label for moderate dry eye disease due to its anti-inflammatory properties, as supported by XYZ study.” 
2. Risks and benefits discussion
   • Document that the patient was informed of the following: 
   • Medication’s FDA-approved vs. off-label use
   • Potential risks, benefits, and alternatives
   • Uncertainties related to off-label efficacy or safety
3. Patient consent
   • While verbal consent is often sufficient, written consent, such as a signed form, is advisable for high-risk medications or novel applications. Example: “Patient verbally consented to off-label use of doxycycline 50 mg daily for meibomian gland dysfunction after discussing risks (eg, GI upset, photosensitivity) and benefits (eg, reduced inflammation).”
4. Follow-up plan 
   • Note important monitoring parameters (eg, IOP check in 2 weeks to assess for steroid response) and contingency plans for adverse effects (i.e., if steroid response is present, add topical beta blocker and taper steroid).   

Legally, a signed consent form is not universally required for off-label use, but it provides an extra layer of protection. Requirements vary by state and institution, so check your local regulations.

For example: 

• Low-risk scenarios (eg, using artificial tears off-label): Chart notation of risks/benefits may suffice.
• High-risk scenarios (eg, prescribing immunosuppressants): A signed form is prudent. 

Best practice: Develop a standardized consent template for off-label medication use and include it in your EHR. Even if it isn’t mandated, it reinforces transparency and patient trust. 

Chart notation is necessary but not always sufficient on its own. The depth of documentation matters. Avoid vague statements such as “risks discussed.” Instead, specify the following:

• What risks were highlighted (eg, “discussed risk of corneal melt with topical NSAIDs”)
• Patient understanding (eg, “patient acknowledged risks and agreed to proceed”)
• Shared decision-making (eg, “patient declined approved treatment X due to cost concerns and elected off-label option Y”). 

Courts and licensing boards often scrutinize whether the clinician provided enough context to justify the off-label choice. 

Special considerations 

• Pediatric patients: Off-label use is frequent in children due to limited FDA-approved pediatric ocular therapies. Document parent/guardian consent and cite pediatric-specific evidence. 
• Emerging treatments: For novel off-label applications (eg, biologics for inflammatory eye disease), include literature references to establish credibility. 
• Liability insurance: Confirm that your malpractice policy covers off-label prescribing. Some insurers require proof of adherence to clinical guidelines. 

Off-label prescribing is a valuable tool in optometry, but it demands meticulous documentation. While chart notation of risks/benefits is essential, pairing it with written consent (where appropriate) and evidence-based rationale strengthens your defense against liability claims. Document as if your chart will be reviewed in court—because it might be. 

By prioritizing clarity and transparency, optometrists can ethically leverage off-label therapies while safeguarding their practice and patients. When in doubt, err on the side of over-documentation—your future self will thank you!

Research Update:
Commentary on Abstract of the Week

Blair Lonsberry, MS, OD, MEd, FAAO
Diplomate, American Board of Optometry

Dry eye disease (DED), being multifactorial, presents many challenges when trying to determine the best management and treatment options for our patients. The symptoms associated with DED can lead to a significant disruption to the patient’s quality of life. A prolonged disease state can cause permanent changes to the ocular surface, such as conjunctival squamous metaplasia and punctate epithelial erosions of the conjunctiva and cornea. Traditional artificial tear therapy often provides symptomatic relief but typically does not manage the underlying condition. Treating with topical immunomodulators (eg, cyclosporine) and autologous serum (ie, topical drops made from a patient’s own plasma) have become more mainstream, as they can improve both ocular surface health and patient comfort.

Topical insulin, a novel therapy, has been shown to improve persistent epithelial defects, even when compared to autologous serum,¹ and its use has been proposed for patients with ocular surface disruption due to DED.

The purpose of this study was to evaluate the efficacy of insulin eye drops for DED in reducing corneal staining and improving symptoms. This was a retrospective case study involving 16 subjects (32 eyes), in 14 females and 2 males. The main inclusion criterion was a diagnosis of dry eye disease with superficial punctate keratopathy despite at least 6 months of intensive treatment (eg, topical autologous serum, cyclosporine, or both) and acceptance of the off-label use of topical insulin. The primary efficacy endpoint was a change in corneal staining at the 3-month visit. A secondary endpoint was the proportion of subjects who reported an improvement in dry eye symptoms.

Regular insulin (100 IU/mL) was diluted in a normal saline and polypropylene glycol base and subjects were prescribed 1 drop (1 IU/mL) every 6 hours. Subjects were allowed to continue any other dry eye treatment they were already taking. All subjects returned at 1- and 3-months, where a symptom assessment was conducted and ocular health was evaluated. The ocular health assessment consisted of a slit lamp exam to assess conjunctival hyperemia [McMonnies scale] and corneal staining [Oxford scale 0–5]). The subject's baseline subjective symptom mean score (range 0–5) was 3.4 (range was from 2–5) and at the end of the 3-month period, 6 subjects (38%) reported they felt better, 3 (19%) were slightly better, and 2 (13%) were subjectively similar. Both conjunctival hyperemia and corneal staining showed statistically significant improvement from baseline. Overall, subjects reported that topical insulin was well tolerated, and no adverse events were reported (including infections).

The authors concluded that topical insulin treatment resulted in significant improvement of signs and symptoms in patients with DED and superficial punctate keratopathy. They propose that topical insulin therapy is a promising novel treatment in patients with DED and refractory epithelial damage. The mechanism by which topical insulin works is not well understood, but it is thought to enhance proliferation of corneal epithelial cells based on its similarities to insulin-like growth factors (IGF), which have been shown to participate in the growth, differentiation, and proliferation of corneal epithelial cells.²  Insulin has also been shown to improve the regeneration of nerve endings, which could be useful given the neurosensory abnormalities often present in dry eye patients. This could partially explain the symptomatic improvement experienced by the subjects in this study.³

References

1. Diaz-Valle D, Burgos-Blasco B, Rego-Lorca D, et al. Comparison of the efficacy of topical insulin with autologous serum eye drops in persistent epithelial defects of the cornea. Acta Ophthalmol. 2022;100:e912–e919. doi:10.1111/aos.14997
2. Stuard WL, Titone R and Robertson DM. The IGF/insulin-IGFBP axis in corneal development, wound healing, and disease. Front Endocrinol (Lausanne). 2020;11:1–15. doi:10.3389/fendo.2020.00024
3. Wang AL, Weinlander E, Metcalf BM, et al. The use of topical insulin to treat refractory neurotrophic corneal ulcers. Cornea. 2017;36:1426–1428. doi:10.1097/ICO.0000000000001297

Abstract

Topical Insulin, a Novel Corneal Epithelial Regeneration Agent in Dry Eye Disease

Barbara Burgos-Blasco, David Diaz-Valle, Daniela Rego-Lorca, Pilar Perez-Garcia, et al.
Eur J Ophthalmol. 2023 Oct 9;34(3):719-725. doi:10.1177/11206721231206790

OBJECTIVE: To evaluate the efficacy of insulin eye drops for dry eye disease in reducing corneal staining and improving symptoms.

METHODS: In this retrospective case series, patients with dry eye disease treated with off-label use of insulin eye drops were collected. The main inclusion criterion was diagnosis of dry eye disease with epithelial damage and acceptance of the off-label use of topical insulin. Age, sex, type of dry eye disease, time since diagnosis, previous ocular surgeries, concomitant treatment, best corrected visual acuity, symptoms, conjunctival hyperemia and corneal staining were recorded. Data from the 1 and 3-month visit were included.

RESULTS: 16 patients (32 eyes) were treated with insulin (14 females and 2 males; mean age 61.3 ± 16.8 years). 12 patients (71%) were also on autologous serum and 10 patients (63%) on cyclosporine. Symptoms were 3.4 ± 1.3 (range 2–5) when scaled from 0 to 5. Mean hyperemia was 1.0 ± 0.9 (range 0–3) and corneal staining was 2.5 ± 1.3 (range 0–5). After 3 months, 5 patients (31%) referred to be much better, 6 (38%) better, 3 (19%) slightly better and 2 patients (13%) were subjectively similar, mean symptoms being 2.3 ± 1.0 (range 1–4; p = 0.001). Hyperemia was 0.3 ± 0.4 (range 0–1) and corneal staining was 1.1 ± 1.0 (range 0–3; both p < 0.001). Topical insulin was well tolerated with no adverse events.

CONCLUSIONS: The excellent results presented in these case series illustrate topical insulin as a promising treatment in dry eye disease with refractory epithelial damage.

CONFLICT OF INTEREST STATEMENT: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Coding

Ryan Ames, OD, MBA
Owner of InSight Eye Care, Oshkosh, WI

Heal Thyself

I have three little daughters, age 6 and under. It seems like this time of year, we can’t go a few weeks without someone getting sick in our house. Every time we get everyone back up and running to school, work, and activities, another one of us catches a cold, a virus, a stomach bug, or the flu. It reminds me of a patient who has trouble with their corneal function: We take 2 steps forward, then suddenly 3 or even 4 steps back. Every time I think we’re in a good and stable place, the lack of ability for the cornea to maintain homeostasis rears its ugly head, and the patient is back in my chair.

The eyelids have certainly had their moment in the spotlight over the past few years with the reinvigoration of evaporative dry eye disease. Still, the cornea remains a vitally important tissue when considering ocular surface disease. It’s a central focal point when diagnosing, treating, and monitoring progression, and the ability of the corneal epithelium to regenerate efficiently is crucial for restoring normal function and preventing infections, inflammation, and other complications. When ocular surface disease delays or disrupts the corneal regeneration process, our battle to restore homeostasis becomes much more complex.

Tear film stability also relies on a healthy corneal epithelium, as epithelial cells produce mucins that help maintain a smooth optical surface. In dry eye disease, epithelial cell damage exacerbates tear film instability, leading to a cycle of inflammation and further epithelial disruption. Our patients will complain of everything under the sun: dry or watery eyes; foreign body sensation or itching; and—my personal favorite—blurred vision, especially fluctuations.

Managing these patients takes incredible patience in therapy, education, and encouragement. Most of our therapies tend to target broad areas of ocular surface disease: evaporation, inflammation, and overall tear production, but we’re also seeing new innovations to try and address nerve function to create a more balanced environment. When the surface is breaking down and unable to heal itself, these therapies can sometimes feel as if they’re falling short and patients, staff, and doctors can become frustrated with the lack of progress in signs or symptoms. The challenge here is to dig in further and get more curious about why traditional therapies aren’t lining up with our clinical experience or the scientific data as we continue to search for the right treatment to break through this cycle and rehabilitate our patient’s cornea to function properly and heal itself.