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Bilateral, sequential optic neuropathy

  • 1.  Bilateral, sequential optic neuropathy

    Posted 2 days ago
    Edited by Michel Van Lint 2 days ago
    Hello,
    Apologies for the long post. Short and long version below, as well as some images.
    Short version:
    • February 2025: Painful visual loss of the right eye with mild optic disc edema.
    • MRI: Persistent heterogeneous aspect confined to the right optic nerve on T2 without convincing optic nerve enlargement; essentially unchanged over 12 months. No pathological contrast enhancement. Enhanced right optic nerve on T2 STIR.
    • Treatment: Intravenous methylprednisolone and immunosuppressive therapy without meaningful clinical improvement.
    • Outcome right eye: Progressive deterioration to no light perception with complete RNFL and ganglion cell layer atrophy.
    • June 2026: Progressive visual loss of the left eye.  Plasma exchange to no avail.
    • Left eye findings: Goldmann perimetry shows only a small inferotemporal visual field island, while RNFL and ganglion cell layer remain normal on OCT.
    • Additional finding: Absent corneal sensation in the right eye. Right pupil still responds to light.
    • Diagnostic challenge: Persistent enhancement of the right optic nerve, lack of response to aggressive immunotherapy, and sequential bilateral optic neuropathy suggest an infiltrative or neoplastic optic neuropathy, but the initial pain, absence of temporal visual field loss, lack of optic nerve enlargement, and normal left OCT despite severe functional loss are atypical.
    • Current status: Optic nerve biopsy was discussed but declined by the patient. A repeat course of plasma exchange has been initiated while further diagnostic evaluation continues.
    Long version:
    A 47-year-old-aged man from Turkish origin developed visual loss of the right eye with pain on eye movement in February 2025. Examination at presentation demonstrated mild right optic disc edema, and MRI showed a soimewhat heterogeneous aspect on T2 confined to the right optic nerve without convincing optic nerve enlargement. 
    The patient was initially treated elsewhere as presumed optic neuritis with intravenous methylprednisolone, followed by immunosuppressive therapy, but vision progressively deteriorated to no light perception (NLP) in the right eye without meaningful clinical improvement.
    Serial MRI examinations over the subsequent 12 months demonstrated persistent enhancement of the right optic nerve with essentially unchanged imaging. No pathological contrast enhancement. Enhanced right optic nerve on T2 STIR.
    In June 2026, the patient developed progressive visual loss in the left eye. Automated perimetry demonstrated a superior altitudinal deficit. Plasma exchange was given, but to no avail.
    The patient was then sent to me, last week (03 July). Goldmann perimetry showed that only an inferotemporal visual field island remained in his left eye. Notably, there was no temporal visual field defect suggestive of chiasmal dysfunction despite the apparent continuous involvement of the visual pathways on MRI.
    Visual acuity was NLP OD and 1.0 OS. The right optic disc showed diffuse optic atrophy, whereas the left optic disc appeared normal. OCT demonstrated complete RNFL and ganglion cell layer atrophy in the right eye, but entirely normal RNFL and ganglion cell layer thickness in the left eye, despite the profound visual field defect. A mild right RAPD was present with the right pupil still responding to light. An additional unexpected finding was the complete absence of corneal sensation in the right eye, while facial cutaneous sensation was preserved.
    Extensive investigations have failed to establish a diagnosis ("usual" work-up with infectious serology, NMO/MOGAD-screening, lumbar puncture, CT thorax, PET-scan, ...) .
    The combination of persistent MRI enhancement, lack of response to aggressive immunotherapy, and progressive sequential bilateral optic neuropathy raised concern for an infiltrative or neoplastic optic neuropathy. Biopsy was suggested, but denied by the patient.
    Findings that raise questions:
    • initial pain on eye movements
    • absence of temporal visual field loss,
    • lack of optic nerve enlargement despite persistent enhancement
    • normal structural OCT of the left eye despite severe functional loss
    • loss of corneal sensitivity of the right eye
    • interestingly, there is still a pupillary response to light in the right eye
    I was wondering if anyone has any advice for treatment or diagnostic work-up?
    Apologies for any missing information.
    Kind regards,
    Michel
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  • 2.  RE: Bilateral, sequential optic neuropathy

    Posted 2 days ago

    What a tough case!

    Some points of clarification might help:

    How long was it between vision loss in the right eye and MRI? Is it possible contrast enhancement had resolved?

    How much follow-up is there for the left eye after onset of vision loss with normal OCT? Is the GCL normal too? Is there any progressive thinning? Some patients start with supra normal GCL and as such mild to moderate thinning may still leave them in the normal range.

    Any toxic exposures?

    Most cases of optic neuropathy with T2 hyperintensity on MRI, the T2 hypertensity doesn't resolve.

    The non-response to aggressive treatment, lack of contrast enhancement, and stable OCT is suggestive of LHON, although in most cases of LHON while the RNFL may be stable for months to years the GCL does thin within a few months.

    In addition to LHON testing (mitochondrial and nuclear causes) copper deficiency can cause asymmetric optic neuropathy. If the GCL in the left eye truly has been stable for months, might want to consider full field ERG to look for a retina cause such as CAR / AIR.

    If all negative, I agree biopsy the right optic nerve in the blind eye.

    Best,

    Drew



    ------------------------------
    Andrew Carey
    Associate Professor
    Wilmer Eye Institute, Johns Hopkins Medicine
    Baltimore MD
    ------------------------------



  • 3.  RE: Bilateral, sequential optic neuropathy

    Posted 2 days ago
    Michael, 
    I agree with Drew that LHON might be a consideration, but corneal anesthesia points to a meningeal process, especially with positive stir positivity along the right optic nerve to the chiasm. Moreover pain with LHON would be extremely unusual. 

    In my opinion the meninges are involved and lymphoma or arteritis of some type are high on the list. I didn't see CRP or ESR values in your summary, but my presumption is they are normal. 

    In lieu of optic nerve biopsy I would suggest proceeding with temporal artery biopsy bilaterally and/or meningeal biopsy to try and get a handle on what is happening. Considering the duration of the process and treatment to date biopsies maybe difficult to interpret but whatever the process is it is still active despite very aggressive treatment. It is for this reason biopsy now would be a matter of some urgency to try and preserve remaining vision in left eye. 

    I had one similar patient who had a small melanoma on the skin in the V2 distribution of the Trigeminal nerve that was incompletely resected (in retrospect) by Moh's procedure that metastasized to the meninges and optic nerve on the same side. It caused severe visual loss, pain and corneal anesthesia. He responded dramatically to PL1 inhibitors. He never mentioned the melanoma until the 3rd attending physician had questioned him.

    Hope this helps 
    Dave






  • 4.  RE: Bilateral, sequential optic neuropathy

    Posted yesterday
    Edited by Michel Van Lint yesterday

    Dear Dave,

    Thank you so much. 

    CRP/ESR are normal, indeed.

    Lymphoma has been discussed with the neurologist. So far, there have been no obvious clues, but that is part of its challenge, I suppose.

    Meningeal biopsy is a good idea.

    Melanoma: We will need to check with the dermatologist to be sure

    Thank you!

    Michel




  • 5.  RE: Bilateral, sequential optic neuropathy

    Posted 2 days ago
    Agree with Dr Carey. Remember Lhon can spare pupil,






  • 6.  RE: Bilateral, sequential optic neuropathy

    Posted 2 days ago
    GCA is extremely unlikely in a 45 year old, any vasculitis involving the optic nerve should cause GCL thinning within 2-6 weeks. Certainly reasonable to check labs for vasculitis, but a TAB is unlikely to provide any helpful information given the near 0 pre-test probability and will only delay a more useful test and contribute to patient "testing fatigue" and erode trust in the physician.






  • 7.  RE: Bilateral, sequential optic neuropathy

    Posted 2 days ago
    What about labs 





  • 8.  RE: Bilateral, sequential optic neuropathy

    Posted yesterday

    So far, not contributive, unfortunately...

    Michel




  • 9.  RE: Bilateral, sequential optic neuropathy

    Posted yesterday

    Dear Drew,

    Many thanks for your response! 

    Right eye: MRI was done some days after visual loss

    Left eye: No GCL thinning, nor thickening

    Toxic exposures: I did take a general history, but this did not come up - needs to be double checked

    LHON: Failed to mention it (sorry), but it has been screened for

    Full-Field ERG: Good idea, not been done, yet

    Thank you!

    Michel




  • 10.  RE: Bilateral, sequential optic neuropathy

    Posted 2 days ago
    Would still consider ON biopsy on the NLP eye.






  • 11.  RE: Bilateral, sequential optic neuropathy

    Posted yesterday

    Since time appears to be running out, the neurologists and his own eye doctor are also trying to explain this to him. His reason for declining is, that he believes that the future may provide with some sort of optic nerve cure, but if we do a biopsy then this would affect his chances., he stated. I hope we can still change his mind.

    However, timing and place of biopsy are crucial and I honestly don't know if we can still find something after a year. 

    That said, I have had an optic nerve biopsy done for 5 times only and twice it was negative. In retrospect, I still don't doubt the need for one in the negative cases, but it does make one's stomach turn around...

    Michel




  • 12.  RE: Bilateral, sequential optic neuropathy

    Posted yesterday
    I had a case like that but proved to be Wagner,s granulomatosis but actually didn't progress to such devastating visual deterioration though it was steroid resistant but with repeated IV pulse steroids and immunosuppressive treatment vision stopped serrations at 6/60 in the more severely affected eye and 6/18 in the less severely affected right eye 
    The point that I wanted to mentioned is that the diagnosis was made may be in fourth MRI imaging of the orbits over 1 & 1/2 years 





  • 13.  RE: Bilateral, sequential optic neuropathy

    Posted yesterday

    Many thanks everyone for helping brainstorming with this case. The patient is currently admitted in another hospital in which he is followed by some highly skilled neurologists. I have been in close contact with them and they are aware of every suggestion made. I hope to see the patient back later and will update this thread as soon as there is more information available.

    Thank you again,

    Michel