Fungal Subretinal Granuloma
Case Presentation
A 50 yr male with diabetes and on treatment for multiple myeloma (in remission) was admitted with CNS symptoms of meningitis two months back to a general hospital. His imaging showed multiple ring enhancing lesions. He refused lumbar puncture and the neurologist treated him for fungal meningoencephalitis with iv and then oral voriconazole. He improved on the same. Two weeks after discharge he noted decreased vision in left eye and was referred to me. His voriconazole was continuing. His vision was 6/18, and he had a subretinal yellowish lesion in the superior midperipheral retina. There were multiple vitreous cells and fluffy round aggregates all across the vitreous.
The patient was diagnosed as ? fungal endophthalmitis and advised vitreous biopsy and antifungal injections. Patient went elsewhere for second opinion and presented back to me after 10-12 days. The subretinal lesion had grown as had the vitritis. I did limited core vit with posterior pole pvd induction and gave Intravitreal amphotericin and voriconazole. we continued the oral voriconazole.
Pathology exam of vit biopsy material did not reveal myeloma or lymphoma. KOH showed fungal filaments and fungal culture grew aspergillus. Bacterial culture was negative.
I further gave two injections of amphotericin and voriconazole Intravitreal,and started the patient on intravenous amphotericin b.
The vitreous has become much quieter but the subretinal lesion continues to increase in size and there is a localized exudative RD.
Attached are the latest fundus pictures.
Please opine on further management. I am planning complete vit with retinotomy and evacuation of the abscess.
Comment 1
Sir ,
I have Read through the case. I have also consulted an hemato-oncologist/ immunologist.
” He refused lumbar puncture and the neurologist treated him for fungal meningoencephalitis with iv and then oral voriconazole. He improved on the same…..
The vitreous has become much quieter but the subretinal lesion continues to increase in size and there is a localized exudative RD.”
A) patients with hematological malignancies are pre disposed to indolent infections whose primary focus is commonly in the cardiovascular tree or the CNS.
at treatment, the fungal clearance can take a much longer time than expected.
B) The patient has to be explained the value of the diagnostic lumbar puncture which could prove this. A systematic search for other foci should also be undertaken .
c) a CNS route of administration of anti fungals with an in dwelling port could be beneficial as the dose would be much higher with a slightly longer duration of action. also the chorioidal vessels being leaky would ensure therapeutic concentrations subretinally.
d) choice of antifungal will depend on the route of administration, and the willingness of the neurologist to start invasive management. the other option being frequent intra vitreal antifungals.
—————————— —-
I address my further queries to you and Dr MPS sir,
a) would it be prudent to suggest the patient on intrathecal medications (with neurologist assistance ) and observe for progress/regression to a granuloma/scar.
b) wouldn’t a retinotomy cause breakdown of the intact physical barrier of the retina, causing a more disseminated/ fulminant course ?
(the barrier albeit flimsy considering aspergillus)
Awaiting your reply
Comment 2
Fungal endoph can be difficult to manage – I would treat such resistant cases with alternate injections every day for at least 2 weeks – Ampho B on day one and voriconazole on day 2. IV ampho can be toxic and may be difficult to administer over time. Vitrectomy has the potential to make things worse, and would consider it if the above did not work.
regards
Comment 3
Read the whole case a bit late. But would be very hesitant to do a vitrectomy and retinotomy, as very rightly mentioned it breaches an intact physical barrier(however permeable it may be, as regards the blood retinal barrier in the setting of an ongoing infection)
Besides what MPS sir suggested and as aditya has very nicely elaborated(thanks aditya for enlightening) that such a drastic step would be more damaging than helpful.
And as Dr.Avinash had very nicely highlighted in the retnet meet at Hyderabad in 2014, that voriconazole needs to be repeated daily due to its short half life, this would be the place to use it as such.
So I would like to go aggressive but least invasive and not consider surgery as a safe option.
Besides would also like to know that whether a fungal abscess can be drained like that… It has to be a necrotic mass in the choroidal tissue.. Which would be hyperemic , boggy and friable… It could be more catastrophic that what we may presume it to be.
Sorry for the long post.
Regards
Comment 4
You had indicated 2 injections – hence this suggestion. Another alternate to consider is fluconazole intravitreal. Aspergillus however responds to voriconazole best. If getting worse despite daily injections in a reasonably immunocompetent patient, it may be time to revisit the diagnosis – tubercular abscess, lymphoma etc., Would then suggest a FNAB.
regards
Comment 5
Regarding Dr Abhishek’s case I have a query n a very loud thought that along with repeat intra vitreal anti fungal injections can we give antifungals through deep PST route to bring the drug availability to the choroid or it will not make any difference ?
Comment 6
The patient is already receiving oral voriconazole and intravenous liposomal amphotericin B. These should reach the subretinal region well. I am unaware of any PST administration of antifungal… Do other group members have any experience?
Comment 7
Subretinal abscess is due to a focus of choroidal infiltration. There is abundant literature regarding high dose pump based treatment for Cns infections. The hemato oncologist s opinion was to give intra thecally as it would prevent a recurrence in the same or in the other eye. This would score over Intravitreal injections which is therapeutic for the affected eye alone.
As you have now mentioned that he is getting better it is very unlikely that the patient or the neurologist will be willing to undertake such treatments. Newer agents are apparently well tolerated comapred to ampho B, as explained by Dr MPS sir.
Have given subtenon for fungal orbital cellulitis – mucor in diabetics. Not sure of intraocular granuloma
regards
Comment 8
Combining amphotericin with voriconazole will reduce efficacy of voriconazole. As voriconazole is static drug n ampho is cidal. Although voriconazole is very good for aspergillus but simultaneous ampho reduced its efficacy. Pt’s CNS lesion were responding good to voriconazole but adding ampho locally n latter systemically probably caused problems. Voriconazole repeat injections are needed daily in vitrectomised eyes n every alternate day in non vitrectomised eyes.
Comment 9
In the last 6 months i have managed at least 3 cases of endogenous fungal endophthalmitis, one is post renal transplant, one is a pt of SLE, 3 rd case is immunocompetent pt with CNS glioma presenting with fungal granuloma..all are endogenous, vit biopsy confirmed cases of aspergillous fumigatus ( i wanted to present in retnet)..i work in a huge multispeciality hospital..have oppurtunity to see these very commonly
My experience- Intravitreal voriconazole is the better drug
In my 3 cases, one went to panoph-eviscerated, one underwent vit+5000cs silicon oil after series of antifungal inj, 1 pt inspite of multiple voriconazoles succumbed to death ( post renal transplant), one pt which i eviscerated( endogenous panoph) is struggling for life still ( immunocompetent pt) in ICU
For obvious reasons, endogenous fungal has very bad systemic survival rates ( spread to eye means, spread of fungal infection to CNS) even if we are giving antifungals intravitreally, the recovery rate is very poor, oral voriconazole has less bioavailability for eye infection, the pt has to receive intravenous (provided his renal parameters are good), ambizome( liposomal ampho B) has not much role in aspergillous but can given in renal pathology…can give systemic caspofungin along with parenteral voriconazole
Can check systemic aspergillosis by galactomannin test…
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