Intravitreal injection of 99Tc-MDP inhibits the development of laser-induced choroidal neovascularization in rhesus monkeys

Background

The aim of this study was to investigate the safety and efficacy of intravitreal injection of ⁹⁹Tc-MDP, a decay product of ^99mTc-MDP, on the development of laser-induced choroidal neovascularization (CNV) in rhesus monkeys.

Methods

Experimental CNV was induced by argon laser with a small high-energy laser spot. Monkeys were given 50 μL of ⁹⁹Tc-MDP at a concentration of 0.005 μg/mL (n?=?6) or 0.01 μg/mL (n?=?6) by intravitreal injection once a week immediately after laser injury for a period of 56 days. Control animals were treated with the same volume of PBS (n?=?6) in the same way. Eyes were monitored by ophthalmic examination, color fundus photography, fluorescence fundus angiography (FFA), optical coherence tomography (OCT) and histology. Incidences of grade 4 CNV lesions as well as the leakage areas of grade 4 CNVs on the late-phase of fluorescein angiograms were measured in a standardized, randomized and masked fashion fortnightly. The maximum widths and heights of grade 4 CNVs were also calculated by histology at the end of the experiment. Toxicity of ⁹⁹Tc-MDP on the retina was evaluated by electroretinogram (ERG) and histologic analysis.

Results

⁹⁹Tc-MDP reduced the incidences of grade 4 CNVs by 33.33 % and 39.40 % in the 0.005 μg/mL and 0.01 μg/mL groups, respectively, compared with the PBS group on day 28 (P?<?0.05; n?=?6). The leakage areas of grade 4 CNVs were smaller in the 0.005 μg/mL (0.7136?±?0.0283 mm², p <0.01; n?=?6) and 0.01 μg/mL (0.4351?±?0.0349 mm², p?<?0.01; n?=?6) groups than those in the PBS control group (0.9373?±?0.0455 mm²; n?=?6) in a dose-dependent manner on day 28. OCT and histology also showed that the sizes of CNVs were smaller in the ⁹⁹Tc-MDP treated groups than those in the PBS group. Although intravitreal injection of ⁹⁹Tc-MDP led to mild inflammatory reaction in the anterior chamber, histology and ERG findings demonstrated that ⁹⁹Tc-MDP did not cause any change in histological structure or function of the retina (p>0.05).

Conclusions

Intravitreal injection of ⁹⁹Tc-MDP can inhibit the development of laser-induced CNV without toxic effect on retina, suggesting that ⁹⁹Tc-MDP has therapeutic potential for CNV related diseases.