Defining Response to Anti-VEGF Therapies in Neovascular AMD
Defining Response to Anti-VEGF Therapies in Neovascular AMD
The response to treatment may be categorised based on acuity changes immediately after the primary (loading or initiation) phase or during the secondary (maintenance) phase of treatment. However, irrespective of what phase in the treatment, or particular anti-VEGF agent, responses are based on the same parameters as described in Table 1 . VA measurements may be described as 'stable VA' if within ±5 letters from the baseline values.
The response after the primary phase may be:
This primary response is best determined at 1 month following the last initiation dose (that is, at month 4). However, this initial response at month 4 is not always predictive of long-term VA gains, as a proportion of such eyes continue to accrue gains in vision even after month 4 as in the ANCHOR and MARINA studies, HARBOR study and subsequent case series. Furthermore, the PIER, SUSTAIN and EXCITE studies suggested response to treatment may not always reflect the visual outcome after the initiation (loading) initiation phase.
The secondary response uses similar parameters, except that this refers to treatment response in the period following the initiation phase ie at least 4 months from treatment commencement. The response in the primary phase does not necessarily mirror that in the secondary phase.
On the basis of these studies (above), the functional response over both the primary and secondary phases may be further refined to:
Response Based on Change in VA in Terms of ETDRS Letters
The response to treatment may be categorised based on acuity changes immediately after the primary (loading or initiation) phase or during the secondary (maintenance) phase of treatment. However, irrespective of what phase in the treatment, or particular anti-VEGF agent, responses are based on the same parameters as described in Table 1 . VA measurements may be described as 'stable VA' if within ±5 letters from the baseline values.
The response after the primary phase may be:
An optimal (good) response is one where the treated eye gains >5 ETDRS letters from the baseline. The eye of this patient is described as a 'good (optimal) responder'. Some clinicians prefer to use the term 'supernormal response or hyper-normal response' to describe eyes that gain 15 or more letters after the primary phase of therapy. A ceiling effect on improvement—in terms of letters of VA gained—will exist in eyes with good pre-treatment visual acuity.
Primary suboptimal ('partial') response (that is, VA gain of 0–5 letters from the baseline) may be described at the end of the primary phase despite optimal (monthly) delivery of treatment ('partial responder'). Approximately 20–26% of eyes belong to the 'no initial VA gain' group. Some may describe this as a partial response, where there is reduction of subretinal fluid (SRF) and intraretinal fluid (IRF) to 25 and 75% of the baseline but persistence of fluid.
Poor response is defined as no change in VA, that is, VA change of 0 or less letters (but not >4 letter loss) when associated with morphological features of poor response.
Non-response is defined as progressive deterioration of acuity of >5 letters in the treated eye in the primary phase. Such an eye is described as a 'non-responder' to the particular treatment. Primary failures may represent true non-response or may be due to a number of other factors including missing the ideal time window for treatment (that is, treating too late in the disease), treating patients with foveal scarring, which is unlikely to be responsive to anti-VEGF treatment, or other co-existent disease/misdiagnosis (for example, other retinal disease such as IPCV (which forms part of the AMD spectrum), chronic central serous choroidoretinopathy (CSCR), inflammatory or infective choroidoretinitis and so on).
This primary response is best determined at 1 month following the last initiation dose (that is, at month 4). However, this initial response at month 4 is not always predictive of long-term VA gains, as a proportion of such eyes continue to accrue gains in vision even after month 4 as in the ANCHOR and MARINA studies, HARBOR study and subsequent case series. Furthermore, the PIER, SUSTAIN and EXCITE studies suggested response to treatment may not always reflect the visual outcome after the initiation (loading) initiation phase.
The secondary response uses similar parameters, except that this refers to treatment response in the period following the initiation phase ie at least 4 months from treatment commencement. The response in the primary phase does not necessarily mirror that in the secondary phase.
On the basis of these studies (above), the functional response over both the primary and secondary phases may be further refined to:
Initial vision gain after primary phase and maintenance of the initial VA gain without further treatment.
Initial vision gain after primary phase and maintenance of the initial VA gain with further treatment.
Initial vision gain after primary phase and continuing improvement in VA with further treatment in the secondary phase. In the ANCHOR and MARINA studies, 8–14% of eyes gained >15 letters during months 4 to 12. Hariprasad et al have reported that although long-term visual gain may be predicted by VA at month 3 of treatment, some eyes especially those with better VA had a continuing or further gain in their vision when the continued dosing was maintained.
Initial vision gain followed by a loss of VA in the secondary phase. This is often termed as secondary failure.
No initial VA gain after primary phase and no further change in VA in secondary phase.
No initial gain in VA after primary phase, but late gain in 4–12 months ('late response').