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    The largest study yet to investigate the effect of pigment epithelial detachment (PED) size on anti-VEGF therapy outcomes in neovascular AMD shows that complete resolution of the PED may not be necessary for a patient to gain visual acuity.

    It was a subgroup analysis of the HARBOR study, analyzing the effect of baseline PED status (present or absent) and height on visual and anatomic outcomes in patients with neovascular AMD treated with standard-dose (0.5 mg) versus high-dose (2.0 mg) ranibizumab on a monthly or PRN dosing regimen.

    Over 24 months, ranibizumab-treated patients with PED gained a mean visual acuity of approximately 7 to 9 letters, and there was no difference in mean BCVA gains when compared with patients who did not have PED at baseline. Visual gains were similar between monthly and PRN dosing.

    PED due to neovascular AMD is something we frequently encounter in our clinics, but there is little prospective data on anti-VEGF treatment outcomes in this subset of eyes. The data we do have offer mixed results. Despite several limitations, this post hoc analysis provides useful data on the efficacy of ranibizumab in nearly 600 eyes with PE.

    Investigators categorized PED by vertical height: small (35 - 164 μm), medium (164.5 - 233 μm), large (233.25 - 351 μm) or extra-large (352 - 1395.5 μm).

    In all ranibizumab treatment arms, PED height decreased regardless of PED height at baseline. Although patients treated with ranibizumab 2.0 mg had a slightly better anatomic response than those treated with ranibizumab 0.5 mg, no additional visual acuity benefit was seen.

    Additionally, patients who received a higher dose of ranibizumab (2.0 mg) also had higher rates of PED resolution (57% to 70% vs. 45% to 53% with 0.5 mg) but did not experience greater increases from baseline in visual acuity at 24 months (approximately 7 vs. 8 to 9 letters with 0.5 mg).

    In fact, patients with an extra-large PED who received ranibizumab 2.0 mg monthly had a mean decrease in vision at 24 months, although there was a lot of variability in BCVA change from baseline at month 24 in these patients (range, −62 to 30 letters).

    Several other observations of note from this study:

    • More injections were required with increasing PED height.
    • Overall RPE tear rate was low at approximately 5%, but the incidence increased with larger PEDs, confirming previous studies. Lastly,
    • 3-fold higher rate of macular atrophy in eyes with PED resolution at month 24, further supporting the idea that treatment to resolve PEDs completely may not be necessary. It remains unclear from the data whether macular atrophy preceded or followed PED resolution, which has important clinical implications as far as titrating our anatomic endpoint for treatment.

    In addition to the inherent drawbacks of exploratory post-hoc subgroup studies, the authors were unable to differentiate PEDs into specific subtypes; therefore, it is possible responses to treatment could vary based on type. Additionally, only the maximum PED height was analyzed, which likely yields incomplete information since PED morphology can vary widely (e.g. broad and expansive low-lying PED vs. irregular, multi-lobed PED). PED volume, for instance, would have provided more information that could possibly have influenced the outcomes.

    Despite these limitations, this study provides useful information on a patient group we commonly treat.