We appreciate both Dr. Gehrs'(1) careful examination of our study (2) on the efficacy of octreotide in the therapy of severe nonproliferative and early proliferative diabetic retinopathy and the opportunity to respond to her thoughtful comments. In response to her question concerning the baseline scores, the control group and octreotide-treated group baseline Early Treatment of Diabetic Retinopathy Study (ETDRS) scores were not different, with mean(± SD) values of 51.6 ± 4.0 for control and 51.6 ± 4.8 for treated groups. Although a reading center was not used in this pilot study, each retinal specialist used identical criteria for determining when patients reached high risk proliferative diabetic retinopathy, as defined by an ETDRS score of 71. As detailed in our article, the ETDRS score was based on ocular examinations and stereoscopic photographs using standard photographic fields and angiography as needed. There is no reason to believe that the treatment influenced the decision to laser, because the three retina specialists were masked from the study treatment. Patients were specifically instructed not to discuss medications with anyone except the endocrinologist.
Regarding potential confounding factors, no cataract extractions or yttrium: aluminum: garnet laser capsulotomies were performed on the participants during the study. We acknowledge that cataract extractions have been associated with a 20-30% incidence in the advancement of retinopathy(3,4). There are many older uncontrolled retrospective reports of diabetic retinopathy progression after surgical techniques of intracapsular or extracapsular cataract extraction. More importantly, there are also prospective studies using the phacoemulsification technique that indicate no significant advancement of diabetic retinopathy(5). Dr. Gehrs is correct in stating that cataract extraction has also been associated with increasing macular edema and decreasing visual acuity(6), but these were not the end points we used in our study.
Improved glycemic control has been noted in patients receiving octreotide. Octreotide blocks the effect of counter-regulatory hormones such as growth hormone, glucagon, and cortisol, resulting in decreased blood glucose fluctuations and thus facilitating the regulation of blood glucose. However,we do not believe that the beneficial effect observed in the octreotide-treated patients was a result of improved control. As discussed in our report, an earlier study using octreotide alone, without concomitant thyroxine, also resulted in improved glycemic control with mean HbAlc levels of 6.4 ± 0.9% in octreotide—treated patients versus mean values of 8.1 ± 1.8% in conventionally managed patients (7). In this previous study, the octreotide-treated patients and the conventionally-treated patients had an identical incidence of panretinal photocoagulation. Thus, improved glycemic control in our current study cannot explain the efficacy of octreotide therapy. In addition, there are studies suggesting that quickly bringing patients under tight control may actually worsen retinopathy acutely;this effect, however, disappears with a longer duration of tight control(8).
As Dr. Gehrs indicated (1),these results suggest a promising therapeutic approach for treating diabetic retinopathy. However, routine use of octreotide in patients with the progressive vision-threatening disease cannot be recommended until results from ongoing more definitive trials become available.
