This article was originally published in a sponsored newsletter.

This issue takes a closer look at potential gaps in the literature regarding the long-term side effects of the use of isotretinoin, an oral medication often prescribed to treat severe recalcitrant nodular acne, as well as challenges that may exist for eye care providers when co-managing with prescribers. As Dr. McGee mentions in her column, often by the time we become involved with a patient’s care (i.e., usually after dry eye symptoms develop), the damage has already been done.

I’ve treated many patients who have suffered greatly after being prescribed isotretinoin, and most weren’t aware of the potential for developing dry eye disease. From their recollection, the focus of risk/benefit conversations revolved around pregnancy prevention, which is understandable given the association with miscarriage and birth defects. Patients have told me they had to watch educational videos on the topic and take monthly quizzes; sign a contract stating they’d abstain from sex or use two methods of birth control during treatment (and up to four weeks afterward); and take a monthly pregnancy test before refills were granted. Even if there was a discussion about dry eye, I can see how it would pale in comparison to the seriousness of this information, especially to teenagers (the demographic mostly frequently prescribed isotretinoin). And to be fair, it is truly difficult for any non–dry eye sufferer to imagine the fierce potential for how ocular dryness might affect their quality of life.

I brought up my concern of isotretinoin-related meibomian gland damage in conversation with a dermatologist friend not too long ago and was told, “I’ve been prescribing isotretinoin for 15 years and haven’t had a single patient complain to me about dry eye.” This is likely true, but it doesn’t mean it isn’t happening. For some, dry eye symptoms don’t manifest until years later and the connection to isotretinoin isn’t made. And just as our patients don’t think to tell us about GI issues, dry mouth or joint pain unless we ask, I wouldn’t expect them to tell their dermatologist about their dry eye symptoms either.

I support Dr. McGee’s call for better documentation of the long-term ocular side effects of isotretinoin in the literature as well as improved collaboration between eye care and dermatology providers as it relates to the ocular health of our mutual patients.

Amber Gaume Giannoni, OD, FAAO
Editor

Roadblocks in Treating Isotretinoin-related Dry Eye and Strategies to Overcome Them

Isotretinoin, a potent medication for the treatment of acne, has well-documented side effects, including significant impacts on ocular health. Indeed, as you’ll read in Dr. Lonsberry’s eloquent summation of this month’s featured abstract, we know isotretinoin can cause a notable decrease in tear production and a reduction in tear break-up time. These changes contribute to symptoms of dry eye, where patients may complain of irritation, redness and visual discomfort. We often see the manifestation of these detrimental effects on the tear film by an increase in corneal staining.

What isn’t in this paper is how isotretinoin targets sebaceous glands, including the meibomian glands, and how these glands can ultimately be destroyed with isotretinoin treatment. I have young patients whose few remaining glands can be traced back to a round or two of isotretinoin. However, this paper underrepresents the impact to the meibomian glands because it wasn’t analyzed long-term.

In my opinion, the biggest roadblock for eye care providers in managing the serious effects of isotretinoin-related dry eye is that we are not the physicians prescribing this medication. This creates an information gap between providers, which means many patients don’t know all of the potential long-term consequences and aren’t managed effectively during or after the course of treatment.

When I am aware that a patient is going to begin a course or is currently taking isotretinoin, I monitor them closely—typically every one to three months for the duration of treatment— to intervene, if necessary, and stay in contact with their dermatologist. I utilize Omega 3s with GLA (gamma-linolenic acid) to improve meibomian gland function and reduce inflammation. I also employ immunomodulators, neurostimulation and interventional treatments such as heat and expression when needed.

However, I often don’t get the opportunity to intervene because our dermatology colleagues typically don’t involve us in the care of their isotretinoin patients. I don’t believe it’s intentional; it’s simply not part of the workflow associated with prescribing this medication. In an ideal world, patients would have baseline diagnostic testing and then be monitored and treated throughout their isotretinoin course. Risks, benefits and alternative therapies for acne treatment that don’t have long-term ramifications (such as intense pulsed light and laser light therapy) would be discussed thoroughly so that fully informed decisions can be made.

I believe we could have more in-depth discussions like this if the long-term effects of isotretinoin were better documented in the literature, like they are with plaquenil. Plaquenil patients have the benefits of continuity of care, have a clear understanding of the side effects and are managed effectively in most cases. I would like to challenge us to match this referral patterns when patients start isotretinoin therapy, because we have the appropriate knowledge base to properly manage and treat them.

Ultimately, managing isotretinoin-related dry eye requires a multifaceted approach that addresses the underlying tear film instability and meibomian gland dysfunction. By implementing early interventions and providing comprehensive patient care, collaboration between providers can mitigate the adverse effects on the ocular surface and improve quality of life for patients undergoing isotretinoin therapy. Regular monitoring and proactive management are key to preventing long-term damage and ensuring the ocular health of our patients.

Acne is a common skin disease that can affect the ocular system. It has not only a medical component, but also a psychosocial aspect that is often more challenging to address. Patients with acne may feel self-conscious, have low self-esteem and even experience symptoms of depression.¹ The first-line treatment for moderate to severe acne is isotretinoin, which inhibits sebaceous lipid synthesis and suppresses sebum production by up to 90%. While systemic isotretinoin can do wonders for acne, it has also been linked to several ocular complications, such as conjunctivitis, blepharitis, dry eye with contact lens intolerance and impaired night vision.

Studies have reported that all associated ocular adverse events were reversible after isotretinoin treatment cessation. However, none have discussed the recovery time of tear film function or the ocular surface after discontinuation of oral isotretinoin treatment. The purpose of this study was to evaluate these recovery times. This was a prospective, cross-sectional study of 17 patients (34 eyes) who were treated with low-dose oral isotretinoin (less than 0.5 mg/kg/day). Modified Ocular Surface Disease Index (OSDI) score, tear break-up time, Schirmer test and corneal staining were performed in all patients at baseline, during treatment and every two weeks after withdrawing treatment, until the results returned to baseline.

The results demonstrated that tear break-up time appeared to be the most sensitive of the testing. It changed significantly at two weeks after starting treatment and returned to baseline four weeks after treatment withdrawal. Other test results included:

• Schirmer test results: Significantly decreased at six weeks and returned to baseline four weeks after treatment withdrawal.
• OSDI scores: Significantly changed at six weeks after treatment (81.8%) and returned to baseline two weeks (54.5%) after treatment withdrawal.
• Meibomian gland disease: No significant change
• Corneal staining: Significantly positive (90.9%) at six weeks after starting treatment and returned to baseline six weeks after treatment withdrawal.

The authors concluded that low-dose isotretinoin (0.15 to 0.4 mg/kg/day) is effective for treating acne and showed a low incidence of adverse events on the ocular surface. This study confirmed the association between isotretinoin and dry eye using multiple diagnostic factors including patient symptoms, tear film stability and ocular surface damage. However, the results showed that dry eye disease can recover to baseline approximately six weeks after withdrawal from treatment. The most significant limitation to this study was the small sample size. The authors recommended that all patients who are being treated for acne with isotretinoin should have a baseline ocular assessment and be followed through their treatment, as well as six weeks after treatment withdrawal.

Reference(s):

1.  Lekskul M, Thaiwat A, Lekvijittada J. Evaluation of recovery time of tear film function and ocular surface after discontinuing oral isotretinoin treatment for acne vulgaris. Int Ophthalmol. 2023 Sep;43:4683-4688. doi:10.1007/s10792-023-02868-y

Evaluation of Recovery Time of Tear Film Function and Ocular Surface After Discontinuing Oral Isotretinoin Treatment for Acne Vulgaris

Manapon Lekskul, Supitchaya Thaiwat and Jiraporn Lekvijittada
Int Ophthalmol. 2023;43:4683–4688. doi:10.1007/s10792-023-02868-y

PURPOSE: This study aimed to evaluate the recovery time of tear film function and ocular surface after discontinuing systemic isotretinoin treatment.

METHODS: This was a prospective, cross-sectional study. 34 eyes of 17 patients treated with low-dose oral isotretinoin (less than 0.5 mg/kg/day) were enrolled. The modified OSDI score, tear break-up time, Schirmer test, and corneal staining were performed in all patients at baseline, during the course of treatment and after withdrawing treatment every two weeks until the result returned to baseline.

RESULTS: Tear breakup time appeared to be the most sensitive and changed significantly at 2 weeks after starting treatment (P < .001) and returned to baseline at 4 weeks after withdrawal from treatment (P < .001). The Schirmer test results significantly decreased at 6 weeks and returned to baseline at 4 weeks after withdrawal from treatment (P < .001). OSDI scores were significantly changed at 6 weeks after treatment (81.8%) and returned to baseline at 2 weeks (54.5%) after withdrawal from treatment. No significant change was found in the meibomian gland dysfunction. Corneal staining was significantly positive 90.9% 6 weeks after starting treatment and returned to baseline 6 weeks after withdrawal from treatment (P < .001).

CONCLUSION: Dry eye disease can return to baseline levels after treatment withdrawal. At least 6 weeks later, patients could wear contact lenses again, and it was useful to prepare all patients requiring further ocular surgery.

Coding Dermatological Conditions

Our understanding of dry eye disease (DED) has evolved over time. We know it is a multifactorial disease process that often includes underlying dermatological conditions as significant contributors. Optometrists are frequently the first to identify these conditions. I personally have lost count of the number of times I have discussed rosacea with patients who have never been diagnosed with it by their primary care physicians. So how do we go about coding multifactor disease processes? Where do we start? When do we stop?

We have all had patients with clear signs of meibomian gland dysfunction (MGD) who are completely asymptomatic with no other DED findings. In this situation, we would code just the MGD. We have also had patients with symptoms of DED and corneal staining, but their meibomian glands are perfect. Obviously, we should just code DED for those patients. However, when a patient has signs and symptoms of DED and MGD, you should code both.

Let’s complicate the situation a bit. A patient presents with irritated (H57.1) and watery eyes (H04.213) that are causing fluctuating vision (H53.10). On exam, you find superficial punctate keratitis (H16.143) and diagnose DED (H04.123) secondary to MGD (H02.88A/B) that is being caused by rosacea (L71.8). All these diagnoses can stand alone as a final diagnosis, but together they paint a much more complete picture. How should this visit be coded?

If there’s an underlying identifiable dermatological condition, it should be added to the MGD or DED diagnoses. Still, it’s often best to stay with what you know when encountering dermatological conditions that can have ocular surface implications. Dermatitis is a broad category of inflammatory conditions of the integumentary system, and can be described as atopic, seborrheic, contact or dyshidrotic. Unless you have an actual diagnosis from a dermatologist, it is best to document Dermatitis, unspecified (L30.9) if you feel it is appropriate to include the dermatological finding in your assessment and plan. However, keep in mind that it is never a good idea to use an unspecified code as your primary diagnosis.

Coding for symptoms, such as eye pain or visual disturbance, is only necessary when no final diagnosis can be made. Here are three general guidelines to follow when reporting signs and symptoms:

1. When no diagnosis has been established for an encounter, code the condition(s) to the highest degree of certainty. You can use symptoms, signs, abnormal test results or other reasons for the visit.
2. If the signs and symptoms are associated routinely with a disease process, do not assign codes for them unless otherwise instructed by the classification.
3. If the signs and symptoms are not associated routinely with a disease process, assign codes for them.

In the end, the key to coding is to clearly document the reason for the visit and use the code that best represents the final diagnosis. If no diagnosis is made, use the code that most closely represents the signs or symptoms directly related to that day’s encounter.