Macular edema: drying is not repairing.

For reasons still not fully understood, diabetic retinopathy at some stage leads to changes in the retina, the most prominent part of which is alterations in the blood retinal barrier and appearance of macular edema which adversely affects vision. Treatment is then decided and applied. Central questions one should ask for evaluating the treatment strategy are: what is the goal of treatment and what are the actual benefits?

The ideal goal of a treatment would be to repair changes due to diabetic retinopathy and then fully restore vision. Laser treatment up to now has not had great success: it destroys some more of the retina to help preserve other parts. Used for diabetic macular edema, the assigned goal was to limit loss of vision for at least a few years. Laser achieves this goal not always at an individual level but at least at a group evaluation level: mean visual acuity of a group treated with laser is maintained and even after some more years may increase slightly.1 This is a one-time (or few-times) treatment, similar to surgery and evaluated as such.

Intravitreal drugs, even with their burden of multiple injections and follow-up, brought new hope. The goal was much more ambitious: restoring vision. Here the mechanisms were also much better understood than for laser therapy. The drugs are able to restore blood retinal barrier integrity and then fully treat the edema: a dry normal looking retina (at least at first glance) is obtained.

The enthusiastic presentation of clinical trial results, using graphs with selected scales for abscissa and ordinate, magnifying the few letters of gain in mean visual acuity, also creates the hope for defeated complication and restored vision. However, by contrast to central macular thickness measurements, vision is rarely normalized.

While the benefits of such treatments cannot be denied, in real life, many patients and ophthalmologists are disappointed. Indeed diabetic macular edema is still not defeated. The application of these treatments with all their burdens (including cost) remains challenging. Even if perfectly applied, only a subset of patients really experience visual improvement and this improvement is not so frequently a full restoration. This is in contrast to the anatomical results which are far better with nearly full restoration of blood retinal barrier integrity and retinal thinning.2 This raises new questions that we now have to answer, including: what happened to the retina before or during the period edema developed that cannot be restored despite achieving normal thickness? Do these treatments, on top of their temporary direct effect on the blood retinal barrier, have long lasting benefit? Even if one drug achieves a dry retina, would a combination of medications be able to lead to better results, better vision or at least simpler follow-up period with less repeat injections?

Shoeibi and co-authors with their sophisticated study whose results are reported in this issue of Journal of Ophthalmic and Vision Research address several of these still answered questions.3 Is there any real benefit of combining triamcinolone with bevacizumab? In accordance to their previous publication on the short-term effect of such therapy,4 the answer seems to be “no”. Each of these drugs alone achieves it assigned goal, restoring the blood retinal barrier integrity, but combining the two drugs does not do any better. There is no “good surprise” beneficial effect of combination therapy, even not in terms of the number of injections in the long term. Indeed after 6 months, eyes required very few injections in both groups and all still did better than control eyes.4 The unanticipated low need for reinjections in these laser treated patients (which has also been reported is second year studies even without laser therapy) may be the answer to the question concerning the long term benefit of treatment. Whether this was due to spontaneous healing of diabetic macular edema or a direct effect of the agents on the retina, the result is there: treated eyes did better than controls.4 This is an optimistic conclusion, suggesting that even if only a loading dose of three injections is performed and then for real life issues the following management is not optimal, investments made by the patient and efforts by caregivers are not abated.

Laser therapy and intravitreal drugs are current treatment modalities. However, looking at the level of final visual acuity in this study and many others, clearly indicates that we are not at the final station: today we are able to dry the macula and achieve some benefit, but we are still unable to preserve or fully restore vision: drying is still not repairing.