HK Ocular Surface Newsletter Issue No. 3 Jul 2023

OPHTHALMOLOGY

Last updated: 24 July 2023 | In: Ophthalmology, Therapeutic Areas

Article Keywords

topical cyclosporine, ocular graft-versus-host disease, conjunctival injection, chronic dry eyes, inflammation, atopic dermatitis, dupilumab-induced conjunctivitis

DR. ALLIE LEE
Clinical Assistant Professor
Department of Ophthalmology,
LKS Faculty of Medicine,
The University of Hong Kong

OCULAR GRAFT-VERSUS-HOST DISEASE (GvHD): THE DOWNSIDE OF SUCCESS

Haematopoietic stem cell transplantation (HSCT) remains to be the last hope of survival for many haematological malignancies and non-malignant disorders.¹ Graft-versus-host disease (GvHD) occurs in allogeneic HSCT recipients when donor T cells identify normal host tissues as foreign and attack them.² It can cause serious complications of multiple organ systems, for example, skin, liver, lungs, gastrointestinal tract, eyes and joints.³ Ocular involvement is common, affecting up to 70% of allogenic HSCT patients.⁴ With expanding indications for HSCT and improved survival thanks to new advances in transplant medicine, ophthalmologists are more likely to encounter patients with long-term ophthalmic complications following allogenic HSCT.

Ocular GvHD typically affects the ocular surface, including the cornea, conjunctiva, as well as meibomian glands.⁴ Histopathologically it is characterized by immune-mediated inflammation.⁴ Dr. Lee shared that the most common clinical presentations were conjunctival injection and chronic dry eyes. While eyes with severe ocular surface inflammation would present as acute conjunctivitis and diffuse conjunctival injection, eye signs for early low-grade inflammation can be more subtle. Dr. Lee noted that many patients came with apparent “white eyes”, with hidden inflammation localized in the upper lid palpebral conjunctiva, that could only be revealed after careful examination upon lid eversion (Figure 1 & 2).

Untreated ocular surface inflammation could lead to extensive scarring and fibrosis. Many progressed to chronic dry eye disease that significantly affects patients’ visual function and quality of life. In very advanced cases, the cornea would be susceptible to persistent epithelial defects, melting, perforations, and some would eventually require corneal grafting or result in irreversible visual loss. Therefore, ocular GvHD should be identified and treated early to prevent long-term complications.

Figure 1: Bulbar conjunctiva appears white with minimal injection
Figure 2: On upper lid eversion, palpebral conjunctival is injected with subconjunctival scarring (arrow)

In Dr. Lee’s practice, the first step would be determining the degree of inflammation. For patients with highly inflamed ocular surface, a short course of topical corticosteroids for four to six weeks will be considered first-line. Topical cyclosporine A (CsA) will then be added as a steroid-sparing agent. “I found commercially available topical CsA to be both efficacious and well tolerated in most patients. I would usually start with CsA daily or BD, titrate up or down on a case-by-case basis, up to QID. In general, I would prescribe topical CsA for six to 12 months”, said Dr. Lee. It is very common for patients to experience mild irritation after topical CsA instillation in the first one to two weeks. Refrigerated eyedrops and instilling lubricants prior to topical CsA are useful in relieving the discomfort, as reported by some patients.

In the past, there has been a lack of designated services and focused expertise for ocular GvHD patients in Hong Kong. With this service gap in sight, a multidisciplinary collaboration between ophthalmologists and the bone marrow transplantation team has been established in Queen Mary Hospital and Grantham Hospital to provide subspecialty eye care for HSCT patients. This includes a direct referral pathway of HSCT patients to join a regular ocular surface disease screening programme, together with a fast-track clinic to offer timely treatment for acute cases. This cohort covers 85–90% of all HSCT patients in our locality in that period and no severe ocular surface complications have been reported since its establishment in 2021.

Case Sharing

A 48-year-old man with acute myeloid leukemia underwent HSCT from a matched unrelated donor in 2013. Prior to HSCT, he had no ocular surface diseases. However, he developed severe dry eyes that affected his activities of daily living since 18 months post-transplant. He had multiple punctal plugs over the years with no marked improvement and was maintained on lubricants Q1H.

This patient consulted Dr. Lee for increasing ocular discomfort and red eyes around 10 years post-transplant. On slit-lamp examination, both bulbar and palpebral conjunctiva were injected (Figure 3), with diffuse punctate epithelial erosions and decreased tear break-up time (Figure 4). On lid eversion, subconjunctival scars were found in bilateral upper lids. Both eyes were tested positive on InflammaDry^®, a point-of-care test for elevated tear inflammatory marker matrix metalloproteinase-9 (MMP-9). Systemically he adhered to regular follow-up at the haematologists’, and showed no evidence of thyroid or rheumatological disorders. The clinical features were compatible with flare-up of ocular GvHD-related inflammation and dry eyes. Treatment aimed to control ocular surface inflammation and improve lubrication. The patient was thus prescribed CsA 0.1% nocte, preservative-free lubricants Q1H and eye gel nocte. At four-week follow-up, both inflammation and dry eye symptoms improved.

Figure 3: Ocular surface inflammation with injection over bulbar and palpebral conjunctiva
Figure 4: Diffuse punctate epithelial erosions and reduced tear break-up time

Key Takeaways

Ocular GvHD poses the risk of severe inflammation and dry eye diseases if left underdiagnosed and untreated. Ophthalmologists should aim for early diagnosis and treatment to prevent long-term debilitating complications. Topical CsA 0.1% can be considered in patients with inflammatory episodes and first-line treatment failures. In Hong Kong, there is a collaborative effort between ophthalmologists and haematologists to provide a designated subspecialty service for HSCT patients, thereby optimizing care and raising disease awareness.

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DR. TOMMY C.Y. CHAN
Specialist in Ophthalmology
Hong Kong Sanatorium & Hospital

MANAGEMENT OF RED EYE IN ECZEMA PATIENTS

Atopic dermatitis (AD), or eczema, is a chronic inflammatory skin condition that is often associated with ocular comorbidities.⁵ Moderate-to-severe eczema patients are more likely to develop conjunctivitis and keratitis than the general public.⁶ Other potential complications include blepharitis, keratoconus, glaucoma, cataract, and retinal detachment.⁵ Additionally, pruritus in AD stimulates eye rubbing⁷, which Dr. Chan warned may transfer germs from the hands to the ocular surface, leading to infectious conjunctivitis or conjunctival erosion. He further added that habitual eye rubbing can lead to mechanical trauma, including keratoconus and retinal detachment.

Medication use also plays a role in the development of ocular complications. The most commonly prescribed AD treatment is topical corticosteroids, which may lead to the development of glaucoma and anterior subcapsular cataract.⁸ The recently approved biologic dupilumab for AD treatment, on the other hand, is associated with conjunctivitis.^9,10 “I have encountered some cases of dupilumab-induced conjunctivitis, mostly mild in severity and without appearing to have any distinct clinical characteristics,” said Dr. Chan. He mentioned that dermatologists usually can manage patients with dupilumab-associated conjunctivitis with topical fluorometholone; additional follow-ups by ophthalmologists are rarely required. For patients who flare up after terminating topical corticosteroids, Dr. Chan recommends steroid-sparing agents such as topical cyclosporine A (CsA) to alleviate signs.

“It is important to identify the types rather than the causes of conjunctivitis, as management differs,” said Dr. Chan. For allergic conjunctivitis, he usually prescribes artificial tears to dilute allergens for mild cases and adds antihistamines or mast-cell stabilizer eyedrops to reduce allergies when necessary. Topical corticosteroids would be considered for severe allergic conjunctivitis. For infectious conjunctivitis, Dr. Chan usually prescribes antibiotics in combination with topical corticosteroids empirically for a week. Fluoroquinolones like levofloxacin and ciprofloxacin, and aminoglycosides like tobramycin are commonly used antibiotics. The choice of antibiotics depends on the doctor’s preference or the patient’s medical history of drug allergies, if any.

In addition, Dr. Chan shared his experience regarding the use of topical CsA. Patients with allergic conjunctivitis who are prone to relapse after the termination of topical corticosteroids may be considered for topical CsA. In Dr. Chan’s routine practice, he prescribes topical CsA for three months as patients’ first trial. The dosing schedule would be QID during the first month, and he would gradually taper the medication as the condition improved. “Whether topical CsA 0.05% or 0.1% is preferred depends on the patient’s tolerance; however, lower-concentration topical CsA treatment efficacy is usually less ideal,” Dr. Chan commented.

Case Sharing

An 8-year-old boy with eczema who had recurrent allergic conjunctivitis was presented to Dr. Chan in 2019. Ophthalmic examinations revealed limbitis and conjunctival hyperemia (Figure 5 & 6). Dr. Chan prescribed topical corticosteroids TID or QID and added topical CsA 0.1% QID, considering that the frequent recurrence of the disease required high-dose topical corticosteroids. The patient experienced stinging after the instillation of topical CsA, so lubricant eyedrops were administered to alleviate his discomfort prior to topical CsA instillation. Redness faded, and limbitis resolved after two weeks of treatment.

Topical corticosteroid therapy was then stopped, and the patient continued on topical CsA 0.1%. Symptoms improved, with the sclera almost normalized after the two-week topical CsA monotherapy. The patient continued topical CsA 0.1% QID for two more months and subsequently had the dosage titrated down from QID to BD as maintenance. The patient remained symptom-free on maintenance therapy for six months, and the prescription was changed to PRN. He reported less frequent flare-ups throughout the three years, and the frequency of using the topical CsA 0.1% is approximately two to three times per month as of now.

Figure 5: Upper palpebral conjunctiva before treatment
Figure 6: Lower palpebral conjunctiva before treatment

Key Takeaways

Patients with eczema have an increased risk of ocular comorbidities due to the disease or medication use. Instead of repeated prescriptions of antihistamines or topical corticosteroid monotherapy, Dr. Chan encourages the early use of more potent medications, such as topical corticosteroids in combination with topical CsA in eczema patients with conjunctivitis, to stop the vicious cycle earlier.

References

Boelens JJ, et al. Front Pediatr. 2020;8:454.

Ferrara JLM & Chaudhry MS. Hematology Am Soc Hematol Educ Program. 2018;2018(1):221–7.

Soleimani M, et al. Surv Ophthalmol. 2023;68(4):697–712.

ClinicalTrials.gov. Available online. https://clinicaltrials.gov/ct2/show/NCT05170347. Last accessed: 07 June 2023.

Hsu JI, et al. Cutis. 2019;104(3):189–93.

Thyssen JP, et al. J Am Acad Dermatol. 2017;77(2):280–6.e1.

Pietruszyńska M, et al. Postepy Dermatol Alergol. 2020;37(2):174–9.

Govind K, et al. J Allergy Clin Immunol Pract. 2019;7(1):298–9.

Simpson EL, et al. N Engl J Med. 2016;375(24):2335–48.

Lin TY, et al. Pharmaceutics. 2023;15(4):1031.

Disclaimer: This article is brought to you by Santen Pharmaceutical (Hong Kong) Limited. Contribution of the articles by the healthcare professionals are made on an honorary basis. The contents contained herein represent the healthcare professional’s opinions based on his/her own clinical experience.

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This article is not medical advice. Patients should seek personal assessment by a licenced specialist. Physicians are recommended to read the full publication(s) as cited in the article before making medical decisions. This article does not supersede nor replace the published article(s).