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Focusing on treatment of orbital inflammatory disease


inflammation in eye

Immunomodulatory drugs are cornerstone of care for minimizing morbidity. Establishing a diagnosis guides targeted patient care. 

Medical management of orbital inflammatory disease (OID) is based on the use of non-specific and specific immunomodulatory drugs. Patient care is optimized by determining underlying etiology for the inflammation, according to Louise A. Mawn, MD, professor of ophthalmology and neurological surgery, Vanderbilt University Medical Center, Nashville, TN. 

“Orbital inflammation is a response of the immune system and not a diagnosis in itself,” she explained. 

When faced with medical management, Dr. Mawn said physicians first have to know what it is they are treating and how to manage the unknown. 

“I tell patients who present with orbital inflammation that we may be at the beginning of a journey with a path we will walk together to better define their disease so that we can tailor the treatment,” she said. 

Related: Management of ocular inflammation and pain using novel insert  

Diagnostic challenge
Orbital inflammation can develop in association with several diseases, including infectious entities, structural problems, autoimmune disorders, and neoplastic diseases. It may also be idiopathic. 

“If I call the inflammation idiopathic, however, I tell patients that we learned in medical school that the idiots do not know the pathology, and that I will continue to give vigilant attention to their disease because it may be in evolution,” Dr. Mawn said. “We only apply the term ‘nonspecific orbital inflammation’ to describe a condition after we have exhausted a search for a specific cause.” 

Diagnosis in patients with OID involves a complete review of systems and physical examination, a laboratory work-up, imaging, and “bladeless” biopsy, but tissue biopsy may also be necessary.

Related: Ocular surface inflammation: Vicious cycle of ocular surface disruption 

The review of systems homes in on identifying symptoms of joint, gastrointestinal, sinonasal, and skin disease, as well as any personal or family history of endocrine or immune disease.

The evaluation also includes a drug history, recognizing that some medications (e.g., bisphosphonates and propylthiouracil) can cause orbital inflammatory reactions.  

A CT scan is generally performed as initial imaging because of ease of access and lower cost compared with MRI. Patients with orbital inflammation may present first to the emergency department where a CT scan may be done.

Related: Novel drugs + delivery systems ease ocular pain and inflammation 

Minimizing morbidity 
Regardless of the etiology of the inflammation, the immune mediators causing the inflammation are the same. Options for controlling the immune response include agents that act via non-specific pathways and biologics that have specific targets.

Treatment selection, however, may be dictated by insurance, considering that some third-party payers require using a stair-step approach to treat inflammatory disease.

“We may have to start with steroids, which are the least expensive option, then ramp up to other non-specific immune modulators before moving to specific agents,” Dr. Mawn said. 

Related: Combination of NSAIDs and steroids reduces CME outcomes 

Steroids are the mainstay of medical management for OID. They act throughout the body and have multiple possible systemic side effects. Baseline evaluations and monitoring require checking body weight, blood pressure, a complete blood count, a complete metabolic profile with lipids, and ruling out tuberculosis. 

“Our goal using steroids is to use the lowest effective dose that will resolve the inflammation for the minimum period of time to avoid side effects,” Dr. Mawn said.

Other non-specific immune modulators used to treat OID include methotrexate, azathioprine, mycophenolate mofetil, and cyclosporine. Dr. Mawn said that methotrexate is another cornerstone of medical management for OID, but it is also associated with a number of side effects.

“The immunomodulatory action of methotrexate is mediated by inhibition of dihydrofolate reductase that leads to depletion of folic acid,” she said. “Many of the side effects of methotrexate can be mitigated by treating patients with 1 mg/day of folic acid.”

Dr. Mawn added that because methotrexate is stored in the liver, some physicians advocate against giving it to patients who use alcohol or who are on other medications that affect their liver. 

Related: Considering BID ocular steroid post-cataract surgery 

Treatment with a specific immunomodulator often starts with an agent that targets tumor necrosis factor-alpha (e.g., etanercept, infliximab, adalimumab). Other biologics, which tend to be more expensive and therefore are reserved for later use, include rituximab, a monoclonal antibody that targets CD20 on B cells and B cell precursors.

Baseline testing for patients who are to be started on rituximab should include a complete blood count with differential and platelets, complete metabolic profile, and serology for hepatitis A, B, and C and HIV.

Other biologics that might be considered for treating OID include tocilizumab, which targets interleukin-6. 

Teprotumumab is an investigational fully human monoclonal antibody targeting the insulin-like growth factor-1 receptor (IGF-1R) that is being evaluated for the treatment of active inflammatory thyroid eye disease. 

Read more by Cheryl Guttman Krader

Louise A. Mawn, MD
E: louise.a.mawn@vumc.org
This article is based on Dr. Mawn's presentation at the American Academy of Ophthalmology 2019 annual meeting. Dr. Mawn has no relevant financial interests to disclose. 

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