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Phenotype Submission - Non-infectious uveitis and iridocyclitis

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Cohort Definition Name: Non-infectious uveitis and iridocyclitis

Contributor Name: Jamie Weaver & Erica Voss

Contributor ORCID: JW = 0000-0003-0755-5191, EAV = 0000-0002-0651-0613

Logic Description: Earliest diagnosis of non-infectious uveitis or iridocyclitis, indexed on the first ever event. This event must either be followed by a second event in the 31 to 365 days in the future or the event must occur at the time of an ophthalmology visit.

Recommended study application: outcome

Assertion statement: This cohort definition was executed on at least one real person-level observational health data source and resulted in a cohort with at least 1 person. Results have not been published yet but in progress.

Submitted cohort definition:
COHORT_ID 8466 - Non-Infectious Uveitis.txt (36.8 KB)

Clinical Description

The following text was created through a combination of clinical expertise, published literature, and ChatGPT. For the ChatGPT prompt, see Appendix A. References suggested from ChatGPT were reviewed.

Overview: Non-infectious uveitis and iridocyclitis, often referred to collectively as non-infectious anterior uveitis, are inflammatory eye conditions affecting the uvea, specifically the iris (iritis) and the ciliary body (cyclitis) in the absence of infection. The uvea is the middle portion of the eye that extends from the iris, ciliary body to the choroid. These conditions are characterized by inflammation within the anterior segment of the eye and can lead to various ocular complications if left untreated. Non-infectious uveitis and iridocyclitis are considered autoimmune disorders, primarily affecting adults but can occur at any age. Disease etiology includes underlying medical condition risk factors such as ulcerative colitis, and Behcet’s disease.

Synonyms include anterior uveitis, non-granulomatous uveitis, or autoimmune uveitis.

Presentation: Presentation includes nonspecific and variable symptoms in the eye such as visual loss, pain, or redness. On examination there may be signs of leukocytes in the eye chamber. Signs of infection are absent.

Patients with non-infectious uveitis and iridocyclitis may present with the following non-specific and variable signs and symptoms:

  1. Eye Pain: Typically described as a dull, aching pain in the affected eye.
  2. Redness (Conjunctival Injection): Conjunctival vessels become dilated, resulting in a red appearance of the eye.
  3. Photophobia: Increased sensitivity to light, causing discomfort in well-lit environments.
  4. Blurred Vision: Impaired vision due to the inflammation and potential complications.
  5. Tearing: Excessive tearing may occur.
  6. Miosis: Pupillary constriction.
  7. Floaters: Patients may notice floaters or spots in their vision.

Diagnostics Evaluation: Assessment requires ophthalmological evaluation of the anterior, middle, and posterior eye chambers.

The diagnosis of non-infectious uveitis and iridocyclitis is primarily clinical and may involve:

  1. Slit-lamp Examination: To assess the degree of inflammation and identify specific characteristics such as cells in the anterior chamber (aqueous flare).
  2. Visual Acuity Testing: To evaluate the impact of inflammation on vision.
  3. Tonometry: To measure intraocular pressure, as elevated pressure can indicate complications.
  4. Fundoscopy: To rule out posterior segment involvement.
  5. Laboratory Tests: Such as complete blood count (CBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) to assess for underlying systemic causes.

Additionally, ancillary tests such as fluorescein angiography and optical coherence tomography (OCT) may be used to evaluate the extent of inflammation and complications in some cases.

Therapy Plan: Non-infectious uveitis should be managed with urgency to prevent complications, preferably starting treatment within 24 hours. Treatment depends on the cause, e.g., viral infections require antiviral medication, while noninfectious causes may include steroids, immunosuppressive agents, or biologics (infliximab, adalimumab).

The standard treatment plan for non-infectious uveitis includes:

  1. Topical Corticosteroids: Steroid eye drops or ointments to reduce inflammation.
  2. Cycloplegic Agents: Such as atropine or cyclopentolate to dilate the pupil and reduce pain.
  3. Systemic Immunosuppressive Medications: In severe or recurrent cases, drugs like corticosteroids, methotrexate, or biologics may be prescribed.
  4. Pain Management: Analgesics or nonsteroidal anti-inflammatory drugs (NSAIDs) for pain relief.
  5. Regular Ophthalmologic Monitoring: To assess response to treatment and monitor for complications.

Treatment may vary depending on the severity and underlying cause of the uveitis and consultation with a specialist is often required.

Prognosis: The prognosis for patients with non-infectious uveitis and iridocyclitis varies:

  • Short-term prognosis (up to 3 months) is generally favorable with appropriate treatment, as inflammation can be controlled.
  • Long-term prognosis (1 year or more) may depend on the presence of complications and the underlying cause. Some patients may experience recurrent episodes, while others may achieve remission with minimal long-term sequelae.

If untreated non-infectious uveitis may lead to complications in eye such as keratopathy, synechiae, cataract.

Differential Diagnosis: Conditions that may present similarly to non-infectious uveitis and iridocyclitis include:

  1. Infectious Uveitis: Such as viral or bacterial uveitis, which require specific antimicrobial treatments.
  2. Angle-closure Glaucoma: Elevated intraocular pressure due to blocked drainage angles.
  3. Herpetic Eye Disease: Including herpes simplex virus (HSV) keratitis.
  4. Scleritis: An inflammation of the sclera, which can also cause eye pain and redness.
  5. Episcleritis: A less severe, self-limiting condition presenting with conjunctival redness.

References:

  1. Jabs DA, et al. Guidelines for the Use of Immunomodulatory Drugs in Patients with Ocular Inflammatory Disorders: Recommendations of an Expert Panel. Am J Ophthalmol. 2000;130(4):492-513. Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel - PubMed
  2. Jabs DA, et al. The Standardization of Uveitis Nomenclature (SUN) Working Group. Am J Ophthalmol. 2005;140(3):509-516. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop - PubMed
  3. Suhler EB, et al. A Prospective Trial of Infliximab Therapy for Refractory Uveitis: Preliminary Safety and Efficacy Outcomes. Arch Ophthalmol. 2005;123(7):903-912. A prospective trial of infliximab therapy for refractory uveitis: preliminary safety and efficacy outcomes - PubMed
  4. Gritz DC, et al. Incidence and Prevalence of Uveitis in Northern California: The Northern California Epidemiology of Uveitis Study. Ophthalmology. 2004;111(3):491-500. Incidence and prevalence of uveitis in Northern California; the Northern California Epidemiology of Uveitis Study - PubMed

Phenotype Definition

Earliest diagnosis of non-infectious uveitis or iridocyclitis, indexed on the first ever event. This event must either be followed by a second event in the 31 to 365 days in the future or the event must occur at the time of an ophthalmology visit.

Phenotype Evaluation

Descriptive data on the cohorts of subjects meeting the definition above can across 5 data sources can be me available upon request. We compared our phenotype, which we refer to as “primary”, to a “broad” definition that only looked for the first occurrence of a non-infectious uveitis or iridocyclitis diagnosis and a “narrow” definition which required subjects have two diagnosis of non-infectious uveitis or iridocyclitis (the second in the 31 to 365 days in the future). Below are some observations made in Cohort Diagnostics during selection of our “primary” phenotype definition.

  • In terms of cohort counts, the “primary” definition selected was in between the “broad” and “narrow” definition. It was more restrictive like the “narrow” definition however the allowance for a single diagnosis during an ophthalmology visit allowed for more subjects than the “narrow” definition to be selected. For example, CCAE had about 470K persons in the “broad” definition, 136K persons in the “narrow” definition, and 292K in the “primary” definition.
  • In terms of cohort overlap, when comparing the “primary” to the “narrow” definition, the overlap ranged from 46%-89% with all additional subjects in the “primary” definition, 11%-54%.
  • For the “primary” definition, generally low incidence (0.09-0.92 per 1k/py, ranging from very rare to rare per CIOMs). Often higher in women and increases with age. Mostly stable over time.
  • When reviewing events close to index (-30, -1 days OR 1, 30 days) or on index (0, 0 days):
    • With conditions, along with eye related diagnosis, pain is an event that comes up near the index.
    • For drug exposures, 27% of subjects in CCAE go on to get prednisolone on the index date. After index we do see acetaminophen exposures second to prednisolone.
    • The number 1 procedure day of index is “Ophthalmological services: medical examination and evaluation, with initiation or continuation of diagnostic and treatment program; intermediate, established patient”. There are also many eye related procedures on index like “Fundus photography with interpretation and report”.

Estimates of measurement error computed through PheValuator can be found in Table 1 below. These results and the results for all Phenotypes Considered can be found in Appendix B.

Table 1: Sensitivity And PPV Estimates from PheValuator on COHORT_ID 8466 across 5 observational databases

cdm cohortId sensitivity ppv
cdm_iqvia_amb_emr_v1979 8466 0.523 0.674
cdm_iqvia_pharmetrics_plus_v2001 8466 0.262 0.645
cdm_optum_ehr_v1990 8466 0.310 0.815
cdm_optum_extended_dod_v2050 8466 0.482 0.783
cdm_truven_ccae_v2044 8466 0.410 0.813

In comparing our selected “primary” definition versus our “broad” and “narrow” definitions, we so that broad typically had the highest sensitivity, “narrow” the lowest, and “primary” tended to recover the “narrow” sensitivity a bit. In terms of PPV, it was the lowest for “broad” and typically highest for “primary”. Thus we felt that “primary” was the best choice given its ability to recover some of the sensitivity from the “narrow” however having a much better PPV over “broad”

Appendixes

Appendix A – ChatGPT Prompt

Please compose a detailed report on the condition: Non-infectious uveitis and iridocyclitis. Aimed at medical professionals, you can include technical terms related to general pathophysiology, but avoid delving into molecular biology. The reader is assumed to be a general practitioner or specialist physician without a background in research. Use Vancouver style for inline citations, ordering them by their first appearance in the text. Ensure every statement is backed by a reference from a publication indexed on the National Library Of Medicine’s PubMed. Do not use double quotes or non utf-8 characters in the output.

Follow the given template. The portions in square brackets [] should be developed based on your expertise.

Use the following template. The portions in square brackets [] are what I want you to develop as an expert.

#Condition: [Name of condition mentioned above.]

##Overview: [Write a concise description of the condition. ]

##Synonyms: [List other names for the condition.]

##Presentation: [Detail the signs and symptoms of condition.]

##Diagnostics Evaluation: [Describe the assessment criteria for Condition. Include suitable tests and potential results where relevant.]

##Differential diagnoses: [Provide a list of conditions that could potentially be mistaken with the condition.]

##Treatment plan: [Outline the standard treatment plan for condition, using bullet points. If multiple treatment options exist, treat each as a separate bullet point. Indicate whether the treatment plan is the current or a previous standard that has since evolved.]

##Prognosis: [Write a brief paragraph on the prognosis for a patient diagnosed with Condition, distinguishing between short term (within the first 3 months after diagnosis) and long term (1 year or more after diagnosis) prognoses.]

##Exclusions: [List any conditions or treatments that must be ruled out at the time of diagnosis. ]

#Ambiguity:[Identify any conditions with similar names to condition but that represent different clinical ideas. Do not include subtypes of condition.]

##Subtypes: [Identify any subtypes of condition.]

##References: [Include at least 10 references that were used in creating this report, ensuring they are indexed on PubMed and compatible with a reference manager.]

Appendix B – PheValuator Results

cdm description cohortId sensitivity ppv
cdm_iqvia_amb_emr_v1979 [964] uveitis xSpec 13747 0.549 0.839
cdm_iqvia_amb_emr_v1979 [964] uveitis prevalence 13748 0.982 0.646
cdm_iqvia_amb_emr_v1979 [964] Non-infectious uveitis (broad) 8468 0.982 0.646
cdm_iqvia_amb_emr_v1979 [964] Non-infectious uveitis (narrow) 8467 0.375 0.624
cdm_iqvia_amb_emr_v1979 [964] Non-infectious uveitis (primary) 8466 0.523 0.674
cdm_iqvia_pharmetrics_plus_v2001 [964] uveitis xSpec 13747 0.295 0.921
cdm_iqvia_pharmetrics_plus_v2001 [964] uveitis prevalence 13748 0.672 0.605
cdm_iqvia_pharmetrics_plus_v2001 [964] Non-infectious uveitis (broad) 8468 0.672 0.605
cdm_iqvia_pharmetrics_plus_v2001 [964] Non-infectious uveitis (narrow) 8467 0.242 0.645
cdm_iqvia_pharmetrics_plus_v2001 [964] Non-infectious uveitis (primary) 8466 0.262 0.645
cdm_optum_ehr_v1990 [964] uveitis xSpec 13747 0.446 0.812
cdm_optum_ehr_v1990 [964] uveitis prevalence 13748 0.589 0.768
cdm_optum_ehr_v1990 [964] Non-infectious uveitis (broad) 8468 0.589 0.768
cdm_optum_ehr_v1990 [964] Non-infectious uveitis (narrow) 8467 0.181 0.825
cdm_optum_ehr_v1990 [964] Non-infectious uveitis (primary) 8466 0.310 0.815
cdm_optum_extended_dod_v2050 [964] uveitis xSpec 13747 0.341 0.901
cdm_optum_extended_dod_v2050 [964] uveitis prevalence 13748 0.679 0.766
cdm_optum_extended_dod_v2050 [964] Non-infectious uveitis (broad) 8468 0.679 0.766
cdm_optum_extended_dod_v2050 [964] Non-infectious uveitis (narrow) 8467 0.275 0.809
cdm_optum_extended_dod_v2050 [964] Non-infectious uveitis (primary) 8466 0.482 0.783
cdm_truven_ccae_v2044 [964] uveitis xSpec 13747 0.351 0.946
cdm_truven_ccae_v2044 [964] uveitis prevalence 13748 0.666 0.786
cdm_truven_ccae_v2044 [964] Non-infectious uveitis (broad) 8468 0.666 0.786
cdm_truven_ccae_v2044 [964] Non-infectious uveitis (narrow) 8467 0.235 0.843
cdm_truven_ccae_v2044 [964] Non-infectious uveitis (primary) 8466 0.410 0.813

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