Case Report: Case 17

Case Presenters

Dr. Kimberley Tan; BSc (Med), MBBS, FRANZCO trained in Ophthalmology at the Royal Victorian Eye and Ear Hospital, Melbourne. He then undertook fellowships in Cheltenham, UK & at the British Columbia Children’s Hospital, Vancouver. He has been the Head of the Department of Ophthalmology at the Sydney Children’s Hospital since 2009 and runs the Neuro-ophthalmology and Adult Strabismus clinic at Royal North Shore Hospital, Sydney. He is a Senior Lecturer at both the University of New South Wales and the University of Sydney. He has been a RANZCO appointed Board
examiner in Paediatric Ophthalmology and Strabismus since 2010.
He is the Lead Visionary in Paediatric Ophthalmology for Sight for All – a South Australian based charity running reverse Fellowship programs in Paediatric Ophthalmology in Myanmar, Vietnam, Cambodia and Laos.
Dr. Kimberley Tan sent us Case 17


Members’ Responses:

1) What investigation would you choose next? [(a) CSF infusion study (b) Formal ICP monitor (c) Sleep study (d) Visual Electrophysiology (e) Dural Venous Sinus Manometry (f) None for now]
7.32% said they would choose (a) CSF infusion study, 24.39% would choose (b) Formal ICP monitor, 2.44% would go for (c) Sleep study, 17.7% said they would choose (d) Visual Electrophysiology, 7.32% opted for (e) Dural Venous Sinus Manometry while 41.46% chose option (f) none for now.

2) Would you recommend any of the following? [(a) Oral Diamox (b) Oral Topamax (c) Corticosteroids (d) Optic nerve sheath fenestration (e) Neurosurgical shunt (f) CPAP (g) Dural Venous sinus stenting (h) No treatment – continue to observe]
58.54% of respondents chose option (a), to recommend oral diamox, 2.44% chose (c) Corticosteroids and another 2.44% chose (d) Optic nerve sheath fenestration while 36.59% opted for (h) No treatment – continue to observe.


Experts Opinion

1) What investigation would you choose next?

2) Would you recommend any of the following?

3) What do you feel is the aetiology to his optic nerve swelling and what other investigations would you have liked in his workup?

4) Please explain the value you place on a standard Lumbar Puncture in these situations? And do you ask for any special instructions in the way it is performed? (Anaesthetics / nitrous / position etc). Do you prefer CSF Infusion studies and / or formal ICP monitoring?

5) How long do you follow these children for? When is it safe to discharge from regular follow up?

Dr. Virender Sachdeva

Dr. Virender Sachdeva is a consultant in Pediatric ophthalmology, strabismus and neuro-ophthalmology
at L. V. Prasad Eye Institute, GMRV Campus, Visakhapatnam, India. He underwent a fellowship in
comprehensive ophthalmology and pediatric ophthalmology at L. V. Prasad Eye Institute, Hyderabad and
has been working at the LVPEI GMRV campus as a faculty since 2008. He also pursued a clinical research
fellowship in Neuro-ophthalmology at the Emory University, Atlanta, USA. He has been actively involved
in the teaching and research pertaining in fields of pediatric ophthalmology, squint and neuro-
ophthalmology. His special areas of interest include amblyopia, complex strabismus, visual field
abnormalities, pupil abnormalities, Optic neuritis, IIH and Neuroimaging. He is concentrating on clinical
research in the newer therapies for amblyopia, atypical forms of optic neuritis, pediatric optic neuritis,
idiopathic intracranial hypertension, and hereditary optic neuropathies in Indian populations. Dr.
Sachdeva has been a peer reviewer for many indexed journals in ophthalmology such as BJO, AJO,
Ophthalmology, Indian Journal of Ophthalmology, International Journal of Ophthalmology and is the
section editor of the BMC Ophthalmology, for pediatric ophthalmology and Strabismus.

I thank Dr. Tan for sharing an interesting and challenging case. From a review of the available information, it appears that the child was detected to have subnormal vision in the right eye (RE), and comprehensive eye examination revealed optic disc edema in both eyes. Given the presence of significant hypermetropia atleast in the right eye and anisometropia, a diagnosis of pseudopapilledema and anisometropic amblyopia seemed reasonable. Investigations such as confrontation visual fields, color vision, and B scan were normal / negative. However, only thing is a close look at the appearance of the optic discs does show obscuration of the peripapillary retinal nerve fiber layer (RNFL) and possible obscuration of the small vessels in both eyes especially nasally, which suggests that the disc swelling is more likely to be true papilledema. It is possible that it was asymmetric at the time of presentation more in the right eye than the left eye which is not unusual. Even OCT of the RNFL shows significant elevation of the RNFL thickness in both eyes, RE> LE, which is even greater than 130 microns, which is again suggestive of true disc edema as patients with pseudopapilledema usually do not have such high overall RNFL thickness. Of note there were no reported symptoms of elevated ICP, child was not obese and there was anemia which will make the diagnosis of elevated Intracranial pressure less likely.

At the same time, MRI brain was obtained which was reportedly normal. Still, CSF opening pressure and was obtained under nitrous oxide sedation and was 13.5 cm of H2O. therefore, a diagnosis of pseudopapilledema was entertained and patient was prescribed refractive correction and patching. However, serial follow-ups showed only slight improvement in best corrected visual acuity (BCVA) in RE and disc appearance was unchanged. Of note repeat evaluation with OCT showed continued increase in the overall RNFL thickness with time, which is conclusive of possible ongoing intracranial hypertension rather than pseudo-papilledema. Therefore, repeat work-up with MRI brain and MRV brain with contrast, and repeat lumbar puncture is totally justified. MRI and MRV brain were reportedly normal and CSF analysis was normal with opening pressure of 18 cm of H2O, which is not conclusive.
This raises the question of further workup as mentioned on slide 14. Various options such as CSF infusion study, formal ICP monitor, sleep study, visual electrophysiology and dural venous sinus manometry were discussed. Among these given normal visual function VEP is least likely to give any useful information. More invasive procedures such as ‘Formal ICP monitor’ might give us more accurate measurement of the CSF pressure than the CSF opening pressure however, all of these are more invasive procedures.

Given the presentation, my suggestions will be the following:

1) Thorough discussion with the neuro-radiologist about presence of subtle signs of elevated ICP, such as posterior globe flattening, vertical tortuosity of the optic nerves, and empty sella, which might be the only signs present in the young patients. Studies have shown that changes from chronic elevated ICP are unusual in pre-adolescent children, so even if these are absent pediatric IIH / intracranial hypertension cannot be completely ruled out.

2) Review of the MRI changes regarding cranio-cervical junction abnormalities that might impede the CSF outflow.

3) Another suggestion is reviewing the MRV brain again to look for flow voids in the cerebral venous sinuses and if suspicious to obtain MRV brain with contrast to avoid missing a CSVT albeit uncommon in this age.

4) Another useful discussion can be regarding the possibility of a dural AV fistula although again unusual to present with only papilledema. Existing literature does suggest such rare presentations and may not be completely rule out without conventional angiography.
– If all of these concerns are addressed, and if we have even subtle signs of elevated ICP on MRI, I will consider a diagnosis of presumed idiopathic intracranial hypertension (presumed IIH) and consider a trial of treatment with oral acetazolamide.
– This is so keeping in view demonstratable papilledema, worsening with time, continued normal visual function including visual fields, patient age and invasiveness of the various procedures.
– It is important to note that studies have shown that even in pre-pubescent children with elevated ICP due to IIH, BMI tended to be low and normal.
– Other treatment options in this case can be reserved based on the response to the treatment as the visual function is good despite disc edema.
– However, a discussion and documentation of the same with parents should be done and if they are still very keen further MRV with contrast, conventional angiography and formal ICP monitoring can be obtained.
As we see in the subsequent course of the patient, there is significant improvement and subsequent resolution of the disc edema following prolonged treatment with oral acetazolamide.

As regards the specific questions:

Q3) What do you feel is the etiology to his optic nerve swelling and what other investigations would you have liked in his workup?
As is clear from the above discussion, in my view the cause of disc edema in the given patient is most likely true papilledema and pediatric IIH is high in the differential diagnosis followed by chronic CSVT, and an indirect AV fistula. My work-up will be focusing on ruling out above and then entertaining a diagnosis of presumed IIH.

Q4) Please explain the value you place on a standard Lumbar Puncture in these situations. And do you ask for any special instructions in the way it is performed? (Anesthetics / nitrous / position etc.). Do you prefer CSF Infusion studies and / or formal ICP monitoring?
As regards the question of the value and accuracy of the lumbar puncture in such a case, it is a difficult situation, but we always try to obtain it under sedation in the standard lateral decubitus position, once the patient has stabilized under anesthesia. Our neurosurgeons and anesthetists usually use sevoflurane for the short anesthesia; however, the values usually do not differ much for nitrous oxide. Literature does suggest no major effect of nitrous oxide on the intracranial pressure. Timing of the lumbar puncture might be important for sevoflurane and nitrous oxide as these might reduce the CSF opening pressure after prolonged anesthesia and should be obtained as soon as patient is stabilized.
However, it is not still free from its own challenges and I have similar experience in 2 patients:
In the first patient, first lumbar puncture was traumatic and could not be relied upon, and the parents refused a repeat Lumbar puncture. Given other findings and after ruling out other considerations, patient was treated on oral acetazolamide and disc edema gradually improved.
In the second patient, where the CSF opening pressure was 16 mm Hg and there were only subtle signs of elevated ICP. Again, with similar considerations, diagnosis of presumed IIH was made and the patient responded well to oral acetazolamide.
If, however, I were to choose I will consider formal ICP monitoring in the workup of the patient after discussion with the parents.

Q5) How long do you follow these children for? When is it safe to discharge from regular follow up?
Overall these children and even adults require a prolonged follow-up. A useful dictum can be to follow-up these patients on active treatment until the disc edema completely resolves, and then gradually taper them of acetazolamide ensuring there is no recurrence of disc edema. On an average, most patients will need a treatment period of 12 to 18 months in my experience. Following this we can follow them up once every 3 months for one year, then every 6 months for a year and if completely free possibly once a year.
Fundus photographs, visual fields and OCT of the peripapillary RNFL can be very useful in the measurements in these patients and can be repeated every 1-2 months in the initial follow-ups.

Dr. Stacey L. Pineles

Dr. Stacy L. Pineles, M.D., M.S. is an Associate Professor of Ophthalmology and Residency Program
Director at the Stein Eye Institute, David Geffen School of Medicine at the University of California, Los
Angeles (UCLA). Dr. Pineles completed her medical school training at the University of Pennsylvania in
2004, followed by subsequent training as an ophthalmology resident (2005-2008) and fellow in pediatric
ophthalmology and adult strabismus at the Stein Eye Institute at the University of California, Los Angeles
(2009). She completed an additional fellowship in Neuro-Ophthalmology at the University of
Pennsylvania (2010), and a Master’s degree in Clinical Investigation at UCLA (2013). In 2010, Dr. Pineles
joined the faculty of the Stein Eye Institute at UCLA, one of the leading centers of vision science in the
world. Dr. Pineles currently runs an NIH-sponsored research program evaluating binocular vision in
children and adults with eye misalignment. Her research interests also include the systemic effects of
pediatric eye disease as well as clinical trials in pediatric ophthalmology. She currently serves as the
principle investigator of an NIH-sponsored multicenter study of pediatric optic neuritis. Dr. Pineles
serves on numerous professional committees within the American Academy of Ophthalmology,
American Association of Pediatric Ophthalmology and Strabismus, and the North American Neuro-
Ophthalmology Society. She travels regularly both nationally and internationally to speak on topics
related to her research in pediatric neuro-ophthalmology and is the author of more than 90 peer-
reviewed publications and 7 book chapters.

1) What investigation would you choose next?
Dural Venous Sinus Manometry

2) What would you recommend?

No treatment – continue to observe

My reason for this is that his visual field is normal, color vision is normal, and he therefore does not seem to have any optic neuropathy even if he does have true edema, which at this point I am not convinced of. This of course is assuming that we trust the opening pressure on the repeat lumbar puncture. If he develops an abnormal visual field or any other signs of optic neuropathy, then I’d consider treatment and/or more investigations. At this point I would be closely monitoring him. As an aside, if the poor vision OD was due to optic neuropathy then I’d expect an APD or at least some VF or color vision issue. I think it would certainly be reasonable to try treating him if there is concern that he is not a reliable test taker but if he and his family are reliable, I’d feel comfortable observing.

3) What do you feel is the aetiology to his optic nerve swelling and what other investigations would you have liked in his workup?
I would have liked to see a fluorescein angiogram and OCT of the nerve with EDI volume scan to more thoroughly evaluate the optic nerve edema and possibility of optic disk drusen. In the absence of increased ICP (checked twice) and normal spinal fluid, normal optic nerve function, and normal neurological exam, MRI/MRV then I’d conjecture that the edema may have been a local process in association with optic disk drusen.

4) Please explain the value you place on a standard Lumbar Puncture in these situations? And do you ask for any special instructions in the way it is performed? (Anaesthetics / nitrous / position etc). Do you prefer CSF Infusion studies and / or formal ICP monitoring?
For lumbar puncture, I ask for lateral recumbent position, and the opening pressure was measured with the use of a standard manometer. I use parameters based on Avery et al. NEJM 2010. I have not found those other tests to be useful unless there are neurologic symptoms.

5) How long do you follow these children for? When is it safe to discharge from regular follow up?
When I am concerned about an optic nerve, I follow the children every 2-3 months for a year. If I don’t see any changes and there are no symptoms, I go to every 6 months for 5 years. Then annually with a visual field after that.

Dr. Selvakumar Ambika

Dr. Selvakumar Ambika is a senior consultant in the Department of Neuro ophthalmology and currently
the Head of the Neuro-ophthalmology services, Sankara Nethralaya (a unit of Medical Research
Foundation, Chennai, India). She has done her MBBS from the prestigious Stanley Medical College –
Chennai & acquired her Post-graduation in ophthalmology followed by a fellowship in Neuro
ophthalmology from the Medical research foundation at the MGR Medical University, Chennai,
Tamilnadu. She has undergone observerships in Neuro-ophthalmology under legends like Dr. Andrew
Lee (University of Iowa), Dr. James Goodwin (University of Illinois), Dr. Averatna Noronha (University of
Chicago) and Dr. Joel Glaser (Bascom Palmer Eye Institution, Miami, USA). Dr. Ambika has been working
in the field of neuro ophthalmology since 20 yrs. She has won the Best Associate Consultant award for
outstanding services in Sankara nethralaya 2003 in addition to winning the Best paper – SD Athwale
award in the Neuro ophthalmology speciality in the All India Ophthalmic Society (AIOS) meeting in 2014.
She has co-authored the SD Athwale award winning papers 4 times for 3 consecutive years at AIOS
Meetings in addition to being awarded the Best paper award in IICTRICMS Neurology 2015. Dr. Ambika
has also authored the Atlas of Neuro ophthalmology (which is the first Indian Atlas in this specialty,
published in 2002) in addition to the atlas in Neuro imaging in ophthalmology published in 2015. Dr.
Ambika has also written many chapters in 12 ophthalmology & 3 neurology text books. She has been an
invited speaker at numerous national and international ophthalmology, neurology and neurosurgery
conferences in addition to having numerous publications in reputed Journals of neuro ophthalmology,
ophthalmology and neurology. Dr. Ambika is an Executive board member of Indian Neuro
ophthalmology society. She is also a Reviewer on the board of the Indian Journal of Ophthalmology, in
addition to being a member of many neurology and ophthalmic societies.

1) What investigation would you choose next?
May ask for VEP and MRV brain and orbit.
VEP to document good optic pathway conduction and no delay in latency of the wave forms as clinically there is no signs of optic neuropathy or elevated ICP. In addition, may r/o venous sinus abnormality.

2) Would you recommend any of the following?
I would have preferred to watch – keep him in close follow-up if patient can come for follow up.
As vision, color vision and fields are stable and no RAPD in this non obese kid who has no significant signs and symptoms of ICP, apart from mild headache – we can watch him!
If close follow up is not possible, I would consider LP, sleep study, after r/o any buried non-calcified Drusen – EDI OCT / will do FFA to check for disc leak, then a Diamox trial if CSF pressure is high

3) What do you feel is the aetiology to his optic nerve swelling and what other investigations would you have liked in his workup?
Probably an optic disc edema [ ODE] without ICP signs –
As the optic disc is crowded with vessels not clearly obscured I would like to r/o a buried non calcified drusen too.
May do a FFA watch for disc leak.
Will do EDI OCT to look for any non-calcified buried drusen.
AF, B scan, even CT ORBIT scan all document calcified drusen but non calcified deeply buried drusens, can be picked by EDI – OCT.
Macular OCT – can also help us to observe the physiological growth related increasing inner retinal layer thickness vs pathological GCL loss which is NA in this case. [there will be increasing macular layer thickness in pediatric population until adolescent age].
Do a sleep study r/o OSA.

4) Please explain the value you place on a standard Lumbar Puncture in these situations? And do you ask for any special instructions in the way it is performed? (Anaesthetics / nitrous / position etc). Do you prefer CSF Infusion studies and / or formal ICP monitoring?
LP and CSF Pressure measurement in pediatric population is useful if it is performed with appropriate measures like NO deep sedation, proper positioning and manometric assessment.
I would prefer – LP in conventional knee chest position. If the child is co-operative no sedation [ideal] or can try mild sedation like IV ketamine. Will not prefer deep sedation – so NO NITROUS [deep sedation can raise the CSF pressure arbitrarily].
I prefer formal ICP monitor may not ask for infusion studies.

5) How long do you follow these children for? When is it safe to discharge from regular follow up?
Keep the child in close follow up may be every 2 months for 6 months
Then once in 4 months for 2 years
Once the vision is stable, amblyopia corrected and stable clinical profile -no optic neuropathy, no worsening of RNL / GCL on OCT DISC AND MACULA – for 2 years then would ask for annual follow-up for 5 years.