Introduction:
Immunotherapy is a potentially effective new cancer treatment. However, these medications may inadvertently harm eyesight. The development of this technique has led to a paradigm change in the treatment of cancer. Still, immunotherapeutic medications appear to have adverse effects on the eyes and other healthy organs in the body, including melanoma, urinary tract, kidney, and lung cancers. Cancer cells can be recognized and destroyed through this treatment by the patient's immune system. One negative effect of immunotherapy cancer medicines is potential vision disorders. Primary care eye doctors should be knowledgeable about the latest cancer medications and any potential ocular side effects.
What Is Immunotherapy?
Immunotherapy is a kind of cancer treatment that makes use of the patient's own immune system to combat the disease. Immunotherapy has the power to alter or strengthen the immune system's ability to identify and battle cancerous cells. Cancer of many different kinds can be treated with immunotherapy. It can be used either on its own or in conjunction with other cancer treatments, such as chemotherapy. Immune checkpoint inhibitors (ICIs), monoclonal antibodies, adoptive cell transfer, and cancer vaccines are important immunotherapeutic strategies.
ICIs have become widely recognized for inhibiting immune cell inhibitory checkpoints, including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1). ICIs efficiently stimulate the immune system to identify and combat cancer cells by accomplishing this. However, this increased immune response can also result in immune-related adverse events (irAEs), which may negatively impact the eyes and other organs.
What Are the Ophthalmic Complications of Immunotherapy?
Ophthalmic complications associated with immunotherapy can affect different structures within the eye. These complications can be self-limiting and mild conditions or severe, vision-threatening entities.
Some common ophthalmic complications include:
1) Uveitis - One common ocular adverse effect linked to ICIs is uveitis. It can result from immunotherapy and is characterized by inflammation of the uvea, the eye's middle layer. Symptoms like photophobia, discomfort, redness in the eyes, and vision blurring are usually present. Secondary glaucoma, posterior synechiae, and cystoid macular edema are among the problems that can result from uveitis, which affects the iris, ciliary body, and choroid. One of the most frequent adverse effects is anterior uveitis.
The use of Pembrolizumab has documented Bechet's like syndrome. Corneal erosions were the ocular symptom of Bechet-like syndrome, and the patient also developed oral and vaginal ulcers on a systemic level. Nivolumab usage has also been linked to uveitis similar to Vogt-Koyanagi-Harada (VKH). Bilateral anterior chamber response and choroidals, in a patient were treated with intraocular and systemic steroids. Three patients reported uveal effusion syndrome following PD1/PD-L1 (programmed cell death protein 1/ programmed cell death ligand 1) therapy.
2) Dry Eye Syndrome - The most common adverse event related to the ocular surface recorded is dry eye syndrome. Inflammation and malfunction of the lacrimal glands may be the cause, which would decrease tear production and cause instability on the ocular surface. Eye discomfort, foreign body sensations, and visual abnormalities may significantly impact patients' quality of life. The usage of PD1/PD-L1 inhibitors has been linked to Sjogren's syndrome. Artificial tears are an easy solution in mild cases. In extreme situations, it may worsen the patient's quality of life and lead to a corneal perforation.
3) Optic Neuritis - An optic nerve inflammation that may develop after immunotherapy. It usually manifests as acute or subacute vision loss, which is made worse by eye movements. It also frequently causes ocular pain. If optic neuritis is not identified, quick treatment with steroids is necessary, as there is a considerable chance that the patient will suffer permanent vision loss. There have been reports of Pembrolizumab-induced optic neuritis.
4) Retinal Disorders - Retinal diseases such as serous retinal detachment, retinal pigment epithelial alterations, and choroidal neovascularization all can occur in immunotherapy-related retinopathy. A MEK inhibitor's first dose may cause MEK inhibitor-associated retinopathy (MEKAR) in the first week of treatment. Bilateral, round, yellow-gray retinal elevations without inferior tracking are the defining features of this creature. Patients on Balversa, Pemazyre, Nivolumab, and Truseltiq frequently get retinopathy.
5) Orbital Inflammation - An uncommon side effect of immunotherapy is orbital inflammation, which might present as symptoms resembling thyroid eye illness. Patients may exhibit symptoms similar to autoimmune thyroid eye disease, such as proptosis, eyelid edema, diplopia, and reduced ocular mobility. It has been reported that using Pembrolizumab can cause myositis, or inflammation of the eye muscles, when there are inflammatory infiltrates on a biopsy. There have been reports of ocular inflammation similar to thyroiditis that cleared with steroids or monitoring.
6) Conjunctivitis - Immunotherapy can cause conjunctivitis, characterized by conjunctiva inflammation, and can cause redness, stinging, tears, and discharge. While typically mild and self-limiting, severe instances usually require topical corticosteroids or other anti-inflammatory medications to relieve symptoms.
How Are Ophthalmic Complications of Immunotherapy Treated?
Early detection and intervention are essential to maintaining excellent eye health for patients receiving various cancer treatments. Most irAEs can be successfully managed with systemic, topical, or periocular corticosteroids. Treating eye doctors should be aware. Nevertheless, corticosteroids must be administered carefully, as they may adversely affect the ICI's therapeutic effect. Collaborating with the oncology team is crucial to ascertaining the correlation between the severity of adverse events and the response to treatment. In the case of severe irAEs, it is equally crucial to consider the risks associated with treatment delays.
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Topical and Systemic Corticosteroids - The first line of treatment for inflammatory ocular disorders brought on by immunotherapy is corticosteroids. When the anterior segment is involved, topical preparations are usually used; however, in cases where the posterior segment manifests or the patient is resistant, systemic treatment may be required.
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Immunosuppressive Agents - Adjunctive corticosteroid therapy may involve immunosuppressive medications such as Methotrexate, Mycophenolate mofetil, or biologics such as tumor necrosis factor inhibitors.
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Lubricants or Artificial Tear Substitutes - To reduce discomfort on the ocular surface and enhance tear film stability, patients with immunotherapy-induced dry eye syndrome may benefit from lubricating ointments, moisture chamber goggles, and artificial tear substitutes.
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Close Ocular Monitoring - To track the course of the disease, evaluate the effectiveness of treatment, and identify any complications early on, routine ocular follow-up is crucial. Close communication between ophthalmologists and oncologists allows prompt intervention and improved patient outcomes.
Conclusion:
Immunotherapy has transformed the way that cancer is treated, but it also carries a risk of immune-related side effects, which makes close observation and collaborative effort essential.
Ophthalmic complications of immunotherapy include a wide range of conditions with different clinical manifestations and therapeutic difficulties. Through progress in understanding the underlying mechanisms and refining treatment approaches, medical professionals can lessen the effects of ocular problems and enhance the visual results and overall well-being of immunotherapy patients.
