Sunday, September 3, 2023

Project : Collective contextual peer review and critical appraisal- Vascular chronic Headache and sudden retinal vessel occlusion response to anti VEGF therapy 

Patient context case report :



PaJR group 


PaJR Conversational decision support system CDSS in a build up to the journal peer review in the group :

[5/6, 8:58 AM] Navya Medicine PG 2022: 35 year old female came with cheif complaints of
-Diminision of vision of right eye since morning 3am
-Headache since 2 days
Patient was apparently asymptomatic 2 days back then started developing diffuse headache sudden in onset,gradually progressive associated with neckpain 
No H/O nausea and vomiting,photophobia,phonophobia
Then since morning 3am had sudden painless loss of vision
No H/O ocular trauma or head trauma
No H/O giddiness,LOC,weakness of both UL and LL
No H/O fever,cough,cold,chestpain,palpitations,orthopnea,PND
H/O some insect bite 2 months back and took herbal medication
N/k/c/o DM,HTN,Epilepsy 
K/c/o hypothyroidism since 5 years  and on tab.thyronorm 100mcg

[5/6, 9:51 AM] Keerthi 2021 Kims Pg: what can we suspect in this case sir? can it be CRVO? 
as it is painless can it be retinal pathology only? or can we even consider optic nerve dysfunction?

[5/6, 9:59 AM] Rakesh Biswas: Fundus images? When are we taking guidance from Vinay to buy the mobile phone Ophthalmoscope that costs 50,000/-?

[5/6, 10:00 AM] Rakesh Biswas: 👆@⁨Afeefa KIMS 2018 ug⁩ She never had history of migraine? As per history here?

[5/6, 10:05 AM] Afeefa KIMS 2018 ug: Sir initially after her last child i.e 13 years back 5 months after delivery she had  pain in left temple region for which she went to Ophthalmologist and was given spectacles she used them for some time and stopped using spectacles 
But her pain didnot subside she used to get headache weekly once or twice since then it was so bad that she was unable to perform her daily activities for which she used to use saridon now sine 3 to 4 days it is very severe initially in left temple region then right temple region and then entire head and neck

[5/6, 10:15 AM] Navya Medicine PG 2022: She also has RAPD grade 3

[5/6, 10:16 AM] Navya Medicine PG 2022: 
Conditions Leading to a RAPD
Occur in lesions affection the visual pathway in front of the lateral geniculate body

Lesions of the Anterior Optic Pathway
Lesions of the optic nerve regardless of the cause of optic neuropathy (e.g., optic neuritis, glaucoma, compression, infection etc.)
Lesions of the optic chiasm
Lesions of the optic tract
Lesions of the pretectum

Lesions of the Retina/Posterior Segment
Large retinal detachments
Ischemia (e.g., ischemic central retinal vein occlusion or central retinal artery occlusion)
Dense macular lesions (chorioretinal scar)[2]

[5/6, 10:39 AM] Rakesh Biswas: If it's retinal vein occlusion what's the next step? Why has she developed it?

[5/6, 11:05 AM] Rakesh Biswas: @⁨Navya Medicine PG 2022⁩ @⁨Keerthi 2021 Kims Pg⁩ If we are unable to find the potential etiologies of CRVO in our patient we can at least ask the Ophthalmology PGs what they think?

[5/6, 11:07 AM] Keerthi 2021 Kims Pg: can it be due to hyperlipidemia in this case sir?

[5/6, 11:09 AM] Navya Medicine PG 2022: They thought that it might be due to any bleeding disorder sir

[5/6, 12:47 PM] Rakesh Biswas: Bleeding disorder as in? Intracerebral hemorrhage?

[5/6, 12:50 PM] Rakesh Biswas: How would hyperlipidemia cause this? Does she have any cutaneous markers for familial hyperlipidemia? 

Did the recent opd patient of chronic pancreatitis (can someone share her case report @⁨Navya Medicine PG 2022⁩ ) have any cutaneous markers?

[5/6, 12:51 PM] Rakesh Biswas: Tell us something about how to solve her problem! 

What have we done since admitting her for the last 24 hours? MRI?

[5/6, 12:52 PM] Rakesh Biswas: Share the image with this finding 

Ask her if any previous history of stroke or anything else

[5/6, 12:58 PM] Rakesh Biswas: Some more history of chronic headache in this patient :

[5/6, 12:50 PM] PMing ug: Sir initially after her last child i.e 13 years back 5 months after delivery she had  pain in left temple region for which she went to Ophthalmologist and was given spectacles she used them for some time and stopped using spectacles 
But her pain didnot subside she used to get headache weekly once or twice since then it was so bad that she was unable to perform her daily activities for which she used to use saridon now sine 3 to 4 days it is very severe initially in left temple region then right temple region and then entire head and neck


[5/6, 12:55 PM] Rakesh Biswas: Is she having this pain since last 13 years? What is the frequency? 

Weekly? 

Monthly?

[5/6, 12:59 PM] Rakesh Biswas: @⁨2018 Tella Shruthi Kims⁩ @⁨Riddhi Kims 2019 UG⁩ Can you tell us more about migraine and retinal vascular occlusion mechanisms supported by data?

[5/6, 1:00 PM] 2018 Tella Shruthi Kims: Yes sir

[5/6, 1:02 PM] Rakesh Biswas: 13 years of chronic headache, weekly once or twice

[5/6, 1:04 PM] Riddhi Kims 2019 UG: Any history of adverse events like pre eclampsia, previous abortions due to complications..? Family history related to pregnancy(eclmapsia, pre eclmapsia) could prompt towards familial thrombophilia..? Which could explain severe persistent headaches and possibly CRVO

[5/6, 1:08 PM] Rakesh Biswas: Can someone provide the patient's advocate's number to Riddhi 'so that she can clarify these directly on phone?

[5/6, 1:09 PM] Afeefa KIMS 2018 ug: Sir no history sir I asked her

[5/6, 1:09 PM] Riddhi Kims 2019 UG: Oh okay ma'am

[5/6, 1:10 PM] Rakesh Biswas: @⁨Navya Medicine PG 2022⁩ @⁨Keerthi 2021 Kims Pg⁩ Ask the Ophthalmology if retinal angiography can help and where can it be done nearest where we can send in our ambulance and get it done 

Review more about managing migraine related retinal ischemia asap @⁨2018 Tella Shruthi Kims⁩
[5/6, 1:28 PM] 2018 Tella Shruthi Kims: Migraine-related retinal ischemia is a rare but serious complication of migraine headaches. It occurs when there is a temporary loss of blood flow to the retina, which can result in vision loss or even blindness if not managed promptly.

The management of migraine-related retinal ischemia typically involves both treating the underlying migraine disorder and addressing the ischemic event itself.

Here are some potential approaches to managing migraine-related retinal ischemia:

Medications: Medications used to treat migraines, such as triptans, may also be effective in reducing the risk of retinal ischemia. Other medications that may be used include aspirin, anticoagulants, and vasodilators.
Lifestyle changes: Adopting a healthy lifestyle can help reduce the risk of migraine-related retinal ischemia. This may include getting regular exercise, maintaining a healthy weight, eating a nutritious diet, avoiding triggers that may cause migraines, and managing stress.
. These tests may include an OCT (optical coherence tomography), FA (fluorescein angiography), or other imaging studies.
Surgery: In some cases, surgery may be necessary to address retinal ischemia. This may involve removing a blood clot, repairing a damaged blood vessel, or performing other procedures to restore blood flow to the affected area.
Follow-up care: It is important to have regular follow-up care with your healthcare provider if you have experienced retinal ischemia related to migraines. Your provider may recommend ongoing treatment or monitoring to help prevent future episodes and manage any long-term effects of the condition.
Overall, managing migraine-related retinal ischemia requires a comprehensive approach that addresses both the underlying migraine disorder and the ischemic event itself. With prompt and appropriate treatment, most people with this condition are able to recover their vision and avoid long-term complications.


[5/6, 1:35 PM] 2018 Tella Shruthi Kims: https://pubmed.ncbi.nlm.nih.gov/34678834/

[5/6, 1:41 PM] 2018 Tella Shruthi Kims: If the attacks are infrequent, such as one per month, then treatment is not necessary. When attacks are more frequent, first-line therapy starts with lifestyle changes that include avoiding dietary triggers such as alcohol and caffeine, controlling stressors like high blood pressure, and ceasing to smoke. If that does not help, then the patient must start a diary to help evaluate the success of the therapy and initiate prophylaxis therapy. It is usually recommended to avoid ergot and beta-blockers in retinal migraines due to the increased incidence of irreversible vision loss. Calcium channel blockers such as nifedipine and verapamil (most effective) are the mainstay of treatment here. Contraindications to calcium blockers include congestive heart failure, hypotension, sick sinus syndrome, cardiac conductive defects, concomitant, and renal or hepatic failure. Other medications such as coumadin and heparin have been used in isolated cases of patients with antiphospholipid antibody syndrome and retinal migraine. Aspirin and antiepileptic drugs have all been shown to reduce the severity of attacks. Abortive therapy is not used in this condition due to the brief duration of episodes; the main focus of treatment would be to reduce the recurrence of attacks. Medications such as Triptans, ergots, and beta-blockers should be avoided in migraines with transient vision loss since there is a concern for exacerbation of vasoconstriction and increasing the risk of potential irreversible visual loss.


[5/6, 2:04 PM] Rakesh Biswas: How does this opinion piece relate to the current patient's requirements? 

Share some literature that may help to consolidate our diagnosis of this patient
[5/6, 2:36 PM] Navya Medicine PG 2022: One month back she had back pain which radiated to hypogastric region for which she was admitted in hospital and took some medication and was told to have renal stones ..after discharge she took herbal medication for renal stones ..Since one week she has severe headache (left  temple region) for which she visited rmp and took 3 injections (unknown) for 3 consecutive days but pain didn't subside and pain is diffuse after that
[5/6, 2:45 PM] Rakesh Biswas: Good lead to factors influencing her outcome of headache and loss of vision
[5/8, 12:01 PM] Rakesh Biswas: Project: Migraine with vascular neurodegenerative asymptomatic basal ganglia encephalomalacia and sudden loss of right eye vision due to retinal vascular occlusion 


[5/8, 11:48 AM] Anonymous student : 35/F CRVO went to X eye institute on saturday sir and they said only if we give anti VEGF within 6 hours there is chance of getting her vision back. but as the time gap is more than 6 hrs they dint give her any treatment and said her vision loss is permanent.they are admitted in X Institute now and are getting more investigations done. They said now we cannot get back the right eye vision so atleast lets make sure that the left eye vision is not lost.


[5/8, 11:50 AM] Rakesh Biswas: But get someone to share the VEGF RCT in a pico format to check if anti-VEGF works even in 6 hours instead of going by hearsay!


[5/8, 11:51 AM] Rakesh Biswas: Yes ask him to review the literature on what investigations are available in this world that can be done in this context!

@⁨2018 Tella Shruthi Kims⁩ @⁨Riddhi Kims 2019 UG⁩ @⁨Arefin Chandpur Chittagong Elective⁩ Another very important patient for the AJND article! Let's do this as well asap. We don't have much time before submission! @⁨Deepika 2021 Kims PG⁩ Who are the other PGs and SRs who are writing this up?


[5/8, 6:34 PM] 2018 Tella Shruthi Kims: The HARBOR trial was a Phase III, randomized controlled trial that evaluated the efficacy and safety of two doses of ranibizumab (Lucentis) and two doses of aflibercept (Eylea) for the treatment of macular edema secondary to branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO). Retinal hemorrhage was one of the key features of the study population. Here is some information about the trial and its results:

Criteria:

Patients with macular edema secondary to BRVO or CRVO were included in the trial

A total of 1099 patients were enrolled and randomly assigned to receive either ranibizumab 0.5 mg every 4 weeks (n=264), ranibizumab 2.0 mg every 4 weeks (n=261), aflibercept 2.0 mg every 4 weeks (n=276), or aflibercept 2.0 mg every 8 weeks after three initial monthly doses (n=298)
The primary endpoint was mean change in best-corrected visual acuity (BCVA) score from baseline to week 24
Results:

Aflibercept was found to be non-inferior to ranibizumab in terms of mean change in BCVA score at week 24 (16.2 vs 14.9 letters gained, p<0.001 for non-inferiority)
Aflibercept 2.0 mg every 8 weeks was found to be non-inferior to aflibercept 2.0 mg every 4 weeks in terms of mean change in BCVA score at week 24 (13.9 vs 18.9 letters gained, p<0.001 for non-inferiority)
The proportion of patients with complete resolution of retinal hemorrhage at week 24 was higher in the aflibercept groups compared to the ranibizumab groups (77.9% and 80.8% vs 61.3% and 62.2%, respectively)
The safety profiles of ranibizumab and aflibercept were similar
Overall, the HARBOR trial demonstrated that both ranibizumab and aflibercept were effective and safe for the treatment of macular edema secondary to BRVO or CRVO, and that aflibercept was associated with a higher proportion of patients with complete resolution of retinal hemorrhage.


[5/8, 6:35 PM] 2018 Tella Shruthi Kims: https://www.nejm.org/doi/full/10.1056/NEJMoa1102673


[5/8, 8:23 PM] Rakesh Biswas: Share a placebo controlled trial in the PICO format 

We need to know if any of them are better than placebo and if yes how much better


[5/8, 8:23 PM] 2018 Tella Shruthi Kims: Okay sir


[5/8, 8:48 PM] 2018 Tella Shruthi Kims: The Protocol T study was a randomized clinical trial that compared the efficacy of three anti-VEGF therapies (bevacizumab, ranibizumab, and aflibercept) to that of a placebo injection in patients with diabetic retinopathy and macular edema. The study enrolled 660 patients who had best-corrected visual acuity (BCVA) of between 78 and 24 letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart, central subfield thickness (CST) of at least 250 μm, and a history of prior treatment for diabetic macular edema.

The primary outcome of the study was the change in BCVA from baseline to 1 year after treatment. Secondary outcomes included the change in CST and the frequency of adverse events.

The results of the study showed that all three anti-VEGF therapies were significantly more effective than the placebo injection at improving BCVA and reducing CST. There were no significant differences between the three anti-VEGF therapies in terms of their efficacy. The most common adverse events were related to the injection procedure, such as eye pain and inflammation.

In conclusion, the Protocol T study demonstrated the efficacy and safety of anti-VEGF therapy in reducing retinal hemorrhage and improving vision in patients with diabetic retinopathy and macular edema. The study also showed that all three anti-VEGF therapies were similarly effective in terms of visual acuity improvement.



[5/8, 8:48 PM] 2018 Tella Shruthi Kims: https://clinicaltrials.gov/ct2/show/NCT02307682


[5/8, 8:54 PM] Rakesh Biswas: Share the details in the PICO format with particular emphasis on the numbers @⁨Raveen 2020 Pg Med KIMs⁩ @⁨Vinay 2020 KIMS PG Med⁩ @⁨Navya Medicine PG 2022⁩ Please guide



[5/8, 9:34 PM] 2018 Tella Shruthi Kims: 


Population: 

32 patients Patients with macular edema secondary to central retinal vein occlusion (CRVO)

Intervention: 

Monthly intravitreal injections of ranibizumab (0.5 mg/0.05 mL) for 3 consecutive months, with further monthly injections if macular edema persisted.

Comparison: 

Sham injections

Outcome: 

Primary outcomes were best-corrected visual acuity (BCVA) and central macular thickness (CMT) at 6 months. After 3 months, BCVA improved significantly more in the ranibizumab group compared to the sham group (mean improvement of 16 ± 14 ETDRS letters versus mean loss of 5 ± 15 ETDRS letters, P = .001). The mean change in CMT was also significantly greater in the ranibizumab group compared to the sham group (−411 ± 200 μm versus −86 ± 165 μm, P < .001). At 6 months, the mean change in BCVA was greater in the ranibizumab group compared to the sham group, but this was not statistically significant (12 ± 20 ETDRS letters versus −1 ± 17 ETDRS letters, P = .067). The mean change in CMT was also greater in the ranibizumab group, but this was only marginally significant (−304 ± 194 μm versus −151 ± 205 μm, P = .05).

Study Design: Prospective, multicenter, randomized, double-masked, placebo-controlled trial.




[5/8, 9:57 PM] Rakesh Biswas: Marginal as suspected 

Can you explain the visual acquity estimates elaborating the points that made these scores 'so that one may have an idea of the clinical significance because statistical significance itself is a sham



[5/8, 10:17 PM] Rakesh Biswas: Explain the BCVA score. How is it calculated?

[5/8, 10:20 PM] 2018 Tella Shruthi Kims: In this study, best-corrected visual acuity (BCVA) was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart sir which consists of letters of decreasing size. The number of letters read correctly at a certain distance is used to calculate a score, with higher scores indicating better visual acuity.

[5/8, 10:21 PM] Rakesh Biswas: That is fine but to understand the significance of these compared numbers in BCVA, we need to understand the BCVA score asap


[5/8, 10:25 PM] 2018 Tella Shruthi Kims: The BCVA score is reported as a fraction, with the numerator representing the distance at which the chart was viewed (usually 20 feet or 6 meters) and the denominator representing the smallest line of letters that the person can read correctly. For example, if a person can read the letters on the 20/40 line of the ETDRS chart at 20 feet, their BCVA score would be 20/40.

In general, a higher BCVA score indicates better visual acuity. For example, a person with a BCVA of 20/20 can read the smallest letters on the chart at 20 feet, while a person with a BCVA of 20/200 can only read the largest letters on the chart at that distance.


[5/8, 10:33 PM] Rakesh Biswas: So what is 60 v 30 BCVA?



[5/8, 10:35 PM] 2018 Tella Shruthi Kims: Scoring in ETDRS is typically done by letter count.  Visual Acuity Score ( VAS ) awards one point for every letter correctly guessed.  Whereas LogMar reduces the score by .02 for each letter correctly guessed.  For example; when a patient correctly reads all lines, including the five letters on the 20/20 line, the VAS score is 100 points


[5/8, 10:36 PM] 2018 Tella Shruthi Kims: 60 letters


[5/8, 10:36 PM] 2018 Tella Shruthi Kims: Correctly

[5/8, 10:40 PM] Rakesh Biswas: In which line?



[5/8, 10:42 PM] 2018 Tella Shruthi Kims: To begin, testing should be done with Best Corrected Visual Acuity ( BCVA ) patients should be either seated or standing 4 meters from the chart.  Beginning with Chart 1, the right eye is tested with the left eye occluded.  

Following the completion of testing the right eye, the left eye is tested with Chart 2 while covering the right eye. 

Reading slowly, each letter is scored as right or wrong.   Correct letters are circled on the scoresheet. Each letter read correctly is assigned a score and each line is totaled at the end of testing.


[5/8, 10:43 PM] 2018 Tella Shruthi Kims: chart -2


[5/8, 10:44 PM] Rakesh Biswas: 👆Here are the correct letters from 'same lines or different lines?


[5/8, 10:49 PM] 2018 Tella Shruthi Kims: I’m guessing as same line sir ,as we consider in Snellen chart reading


[5/8, 10:50 PM] Rakesh Biswas: What is 120 or 136 here?



[5/8, 10:50 PM] 2018 Tella Shruthi Kims: Normal person can read that line standing at 120 feet


[5/8, 10:51 PM] Rakesh Biswas: 138 and 126!!

Why that peculiar odd number?


[5/8, 11:00 PM] 2018 Tella Shruthi Kims: Based on typical visual acuity scores associated with different rows on the ETDRS chart, a score of 20/138 Snellen equivalent would correspond roughly to the 6th row of letters on the chart (which has a visual acuity of approximately 0.9 logMAR), while a score of 20/126 Snellen equivalent would correspond roughly to the 5th row of letters on the chart (which has a visual acuity of approximately 0.8 logMAR).


[5/8, 11:07 PM] Rakesh Biswas: And 152?

They are comparing 

20/126 in ranbizumab group and 20/152 in sham group!



[5/8, 11:12 PM] 2018 Tella Shruthi Kims: Based on typical visual acuity scores associated with different rows on the ETDRS chart, a visual acuity of 20/152 Snellen equivalent would correspond to approximately the 4th row of letters on the chart, which has a visual acuity of approximately 0.7 logMAR.



[5/9, 6:46 AM] Rakesh Biswas: So essentially the number of letters the ranbizumab group was able to read at 6th row, the same number was read by sham group in the 4th row? 

Unless we are able to see how they recorded their visual acquity and what were the factors that made them read more letters (was it just a number to their vision or were they more satisfied with the quality of vision they obtained over and above the sham group), it would be difficult to pronounce judgement in their favor?



[5/9, 6:50 AM] Rakesh Biswas: 👆Oh waitaminute! These are baseline estimates! Does this mean the sham group had worse visual acquity to begin with?


[5/9, 7:19 AM] 2018 Tella Shruthi Kims: Yes sir

[5/9, 7:34 AM] Rakesh Biswas: So how much visual acquity did the sham group recover vs ranbiz group?  Also why select a sham group with worse visual disability than the intervention group?


[5/9, 7:36 AM] 2018 Tella Shruthi Kims: ● SIX-MONTH FOLLOW-UP: The mean SD overall change in BCVA score from baseline to the end of the study was a gain of 12 20 ETDRS letters in the ranibizumab group (P .040; Figure 1) and a loss of 1 17 ETDRS letters in the sham group (P .765; Figure 2).



[5/9, 7:43 AM] Rakesh Biswas: So this is not even statistically significant!



[5/9, 7:50 AM] 2018 Tella Shruthi Kims: BCVA score from baseline to the end of the study was statistically significant only in the ranibizumab group (P = .040) Sir …..but not in the sham group (P = .765). 

A gain of 12 ± 20 ETDRS letters in the ranibizumab group suggests an improvement in visual acuity, while a loss of 1 ± 17 ETDRS letters in the sham group indicates a slight worsening in visual acuity,




[5/9, 8:00 AM] Rakesh Biswas: 0.04 is not statistically significant 

Clinical significance of a few letters gain is doubtful unless the patient tells us how it really panned out overall for that particular individual. Hence the importance of qualitative research side by side quant to answer these vital questions



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