Why Optometry is Awesome.

Avastin vs. Lucentis: Treatment of Wet-AMD

For some time now, the pharmaceutical and ophthalmic industries have been keeping a close eye (if I may) on two drugs produced by Genentech/Roche: Avastin (Bevacizumab) and Lucentis (Ranibizumab). Both are humanized monoclonal antibodies derived from mice, and target and inhibit vascular endothelial growth factor A (VEGF-A), and thus inhibit angiogenesis. Avastin is an important drug used in cancer management, targeting blood supply to tumours, and Lucentis is a potent drug used to treat Wet-AMD via intraocular injections. Lucentis, however, is a few hundred times more expensive than Avastin.

A while back, some ophthalmologists figured that since Avastin and Lucentis are nearly identical in terms of their mechanism of action, Avastin should work well for Wet-AMD too… and apparently it did. However, Avastin isn’t officially approved for the treatment of Wet-AMD, and Genentech/Roche won’t fund clinical trials for the use of Avastin in Wet-AMD, perhaps understandably so, considering the immense cost of research and development of each drug. About 2 years ago, however, a public clinical trial called Comparison of AMD Treatment Trials (CATT) was initiated, and the results of that study have recently been published by the journal, Ophthalmology.

Here’s a link to those results (right click, save as).

Basically, the ophthals were right, and there is no real therapeutic advantage of Lucentis over Avastin; both drugs produce the same kind of improvement in visual acuity after the same kind of treatment regime. So, having followed this study for awhile, I guess I’m curious where things go from here: healthcare cover, future drug design strategies, marketing, etc.

Do you think Lucentis will still be used as a treatment option?

Prisms

When dealing with VG, MR or PC, need to know what prism does:

Prism always shifts image to its apex. Remember that this means, if you need to shift an image up (because Px sees it as lower), induce a BD in the eye that perceives the image as lower.

For example, on the VG, Px is dissociated with a 10 BI LE. Does Px see double image side by side? If no, induce more BI in LE, if yes, occlude LE and ask, does right eye see image on right, and then does LE see image on left? Then, are the images on the same level, like headlights of a car? If yes, no vertical phoria. If no, is the right image higher or lower? If right image higher, means that RE is hypoP. Add BU in front of RE to shift image down until same level, record as 3^ BUR L/R.

Now what about horizontal? Let’s think about PC:

If I put 6 BD in front of RE, the Px should see two line, one above the other. RE should see the upper line. Ask Px if he sees two lines, and are the lines moving? No? Ok, is the live on top on the blue or the yellow, and at what number? Remember that the blue is on the left side of the line and the yellow is on the right side of the line. Now if the arrow on top is pointing to the blue, and resting around the number 8, that is an 8^ XOP.

Think about it, the arrow appears to be on the left (blue side) because the RE (which is seeing the top line) has its gaze turned right (outwards). This means the relative position of the eyes is exophoric (kinda divergent).

Hmm. Ok?

Maddox Rod

The Maddox Rod itself is a red translucent lens made up of a series of parallel plano-convex cyls. When viewing a spotlight through the Maddox Rod, a line perpendicular to the direction of the cyls is seen. Place the Maddox Rod in front of RE, so that RE views a line while LE views spotlight. The point of the Maddox Rod is to break sensory fusion, and the eyes adopt their heterophoric positions. This technique is used to determine the amount of both horizontal and vertical heterophoria.

Horizontal Distance Heterophoria:

• Maddox Rod is placed in front of RE, cyls run horizontal (180)
• Provide spotlight target at distance, in dim lighting
• Direct Px’s gaze to the spotlight, and ask if the line appears on, or L, or R of the spotlight?
• If Px reports line straight through spotlight, Px has no horizontal phoria.
• If Px reports line is L of spotlight, then Px is XOP.
• If Px reports line is R of spotlight, then Px is SOP.
• Use prisms to neutralize phoria and record amount required as amount of phoria. On the phoropter, use the risley prism, aligned in the BI/BO direction.
• Slowly rotate the prism BI if XOP, or BO if SOP, until Px reports line overlapping the spotlight.

Vertical Distance Heterophoria:

• Ok, doing the same, thing except this time, the cyls are aligned vertical (90)
• Px is asked if the line appears above, below, or overlapping the spotlight.
• If line is above, then Px has hypophoria in RE. this equates to a hyperphoria in the LE. neutralize with BD prism in front of LE. (or BU prism in RE)
• If line is below, then Px is RE hyperphoric/LE hypophoric. neutralize using BU prism in front of LE (or BD prism in front of RE)

Recording:

• If fully ortho, then the O+ overlapping sign.
• If horizontal ortho, then O| overlapping sign.
• If vertical ortho, then the O- overlapping sign.
• If horizontal eso/exo, then eg. 4^XOP or 3^SOP.
• If vertical RE hypo/LE hyper, then eg. 2^L/R
• If vertical RE hyper/LE hypo, then eg. 3^R/L

Advantages:

• Easily performed on phoropter or trial frame, or even just handheld with Px’s Rx.
• Easy for Px to understand.
• Very reliable for Px with no accommodation, ie. >60yo.

Disadvantages:

• Spotlight is poor target for accommodation.
• Head tilts or tilted phoropter could screw up result badly.

The Cover Test

Done on Px early in routine screen (maybe after Hx taking and VA assessment).

Two techniques: Cover/Uncover and Alternating Cover.

Most optoms go for the C/U test before doing Alternating because the C/U reveals the presence of a tropia. If no tropia is observed in the C/U, then movements picked up in the Alternating are phorias. The Alternating is very sensitive to deviations, and responses tend to be larger; the concern is that the Alternating test breaks up binocular vision and places stress on the oculomotor system, and recovery may be compromised. If this happens, may be difficult to distinguish tropia from phoria.

C/U Test: assessed at near and distance

• Covered placed in front of RE for ~3 seconds.
• Observe for LE movement.
• If yes, tropia present.
• move nasal = L EXOt, LE moves temporal upon uncover
• move temporal = L ESOt, LE moves nasal upon uncover
• If no, repeat for other eye.
• If yes in both eyes, alternating tropia present (need to define ESO/EXO for both)
• For all tropia, need to note Dx or Nx. eg. Dx L ESOt

If no tropia present in both eyes, check for phorias:

using C/U: again, at Dx and Nx

• cover placed over RE while clinician watches covered eye
• is there movement during cover?
• if yes, nasal, then ESOp [check for temporal movement in recovery/uncover]
• if yes, temporal, then EXOp [check for nasal movement in recov/uncover]
• if no, then ortho, or record as NMD (preferred; “no movement detected”)
• perhaps ask for subjective assess from Px for small phoria?
• estimate extent of phoria, and record. 
• eg. NMD / Nx <3 ESOp (subj.) / Dx 8 EXOp, slow rec. / 5 R ESOt

but also check using alternating:

• cover placed over RE for 3 seconds
• cover moved to LE for 3 seconds
• during transition, watch for movement of eye being uncovered
• movement seen is re-fixation:
• nasal movement = EXOp / temporal = ESOp
• notation as above

Important things to note, the basis of this test is Hering’s law of equal innervation; that is the synergist muscles act in concert in equal amounts. While this is true of tropias, it’s not what you find in phorias (there are exceptions).

*Need to add PX instructions to this: