Risk factors for multiple retinal tears in patients with acute posterior vitreous detachment.

PURPOSE: To evaluate possible risk factors for multiple retinal tears in patients with acute posterior vitreous detachment. MATERIALS AND METHODS: Three hundred and seventy-six consecutive patients presenting with symptoms of floaters and/or flashes were examined. The associations of retinal tears with the duration of symptoms, multiple floaters, flashing, a family history of retinal detachment, peripheral retinal degeneration, lens status, myopia, tobacco dust, and retinal or vitreous hemorrhage were analyzed. RESULTS: Fifty-four (14.4%) of the 376 patients had 71 initial retinal tears. Forty of the 54 eyes had one retinal tear, and 14 eyes had multiple retinal tears. The presence of retinal or vitreous hemorrhage increased the risk of multiple retinal tears 6.1 times using univariate analysis and 7.0 times using multivariate analysis. CONCLUSION: Unrecognized retinal tears in patients with acute posterior vitreous detachment can cause subsequent retinal detachment. It is therefore important to consider multiple retinal tears, especially in patients with retinal or vitreous hemorrhage.

Histological and Immunohistochemical Retinal Changes Following the Intravitreal Injection of Aflibercept, Bevacizumab and Ranibizumab in Newborn Rabbits.

PURPOSE: To analyze the retinal effects of the intravitreally administered vascular endothelial growth factor (VEGF) inhibitors (aflibercept, bevacizumab and ranibizumab) in newborn rabbits. METHODS: Right eyes of 28 two-week-old New Zealand albino rabbits comprised the study population. Four eyes received intravitreal injection of 0.025cc balanced salt solution (BSS) (group I, control group); six 0.25 mg ranibizumab (group II), six 0.3125 mg bevacizumab (group III), six 0.625 mg bevacizumab (group IV), and six 1 mg aflibercept (group V) intravitreally. Blood samples were obtained to evaluate serum VEGF levels. Retinal tissues were examined by light microscopy and immunohistochemical examination (TUNEL and caspase-3 staining) to evaluate the level of apoptosis at the end of the third week. RESULTS: Light microscopic evaluation did not show any retinal abnormality in all study and control eyes. Positive TUNEL staining was present in 16.75 ± 1.25%, 23.6 ± 1.36%, 33.1 ± 5.03%, 49.3 ± 9.3%, and 32.33 ± 8.06% of the eyes recruited in groups I, II, III, IV, and V, respectively. Mean percentage of apoptotic cell counts detected by caspase-3 staining was as follows: 6.75 ± 2.06% in Group I, 12.6 ± 13.44% in Group II, 15.5 ± 1.37% in Group III, 24.0 ± 2.7% in Group IV, and 17.33 ± 1.96% in Group V. TUNEL and caspase-3 staining ratio was found to be statistically higher in all anti-VEGF drug groups compared to the controls (TUNEL stain; p = 0.01, p = 0.01, p = 0.01, p = 0.01; caspase-3 stain; p = 0.024, p = 0.009, p = 0.01, p = 0.01, respectively). Serum VEGF levels were 82.16 ± 1.72 pg/mL, 54.53 ± 12.69 pg/mL, 33.09 ± 17.26 pg/mL, 39.66 ± 5.77 pg/mL, and 36.90 ± 28.14 pg/mL for the control groups II, III, IV, and V, respectively. Serum VEGF concentrations were found to be statistically lower in the anti-VEGF groups compared to the control eyes (p = 0.011, p = 0.011, p = 0.011, p = 0.014, respectively). CONCLUSION: This study demonstrates that apoptosis was induced in the retina of newborn rabbits by intravitreal administration of anti-VEGF agents together with reduction in serum VEGF levels. Among the three anti-VEGF agents, ranibizumab caused the least apoptotic activity in the retina and reduction in serum VEGF levels. In light of our study, we believe that intravitreal anti-VEGF agents should be used with caution as a first line treatment for the treatment of retinopathy of prematurity.

The Effect of Intravitreal Azithromycin on the Albino Newborn Rabbit Retina.

PURPOSE: To evaluate the effect of intravitreal azithromycin on the retina in a newborn rabbit model. METHODS: Twelve, two-week old New Zealand albino rabbits were divided into two groups (six in each). The right eyes of six rabbits received 0.75 mg (0.05 mL) azithromycin and the right eyes of the remaining six rabbits 1.5 mg (0.1 mL) azithromycin intravitreally. Left eyes were served as the control and received the same volume of saline. All eyes were enucleated at the third postinjection week. Retinal histology was examined by light microscopy. Apoptosis of the retinal cells was further evaluated by immunohistochemical staining for caspase-3 and in situ terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate nick-end labeling (TUNEL) of DNA fragments. RESULTS: Light microscopy demonstrated no retinal abnormalities in all eyes. However, retinal nuclear DNA fragmentation was evident in both study groups (33.6% with 1.5 mg and 21.4% with 0.75 mg azithromycin) with the TUNEL method. TUNEL staining ratio was statistically higher only in the second group treated with 1.5 mg azithromycin when compared to the control group (p=0.01 Mann Whitney U test). The ratio of caspase-3 positive cells in the two study groups was 21.5% and 20.2%, respectively. Caspase-3 staining ratio was statistically higher in both study groups when compared to the control eyes (p=0.00, p=0.00 respectively). The difference of TUNEL staining ratio between the two study groups was statistically significant (p=0.028), but there were no statistically significant differences in the two study groups by caspase-3 staining (p=0.247). CONCLUSION: In newborn rabbits, intravitreal azithromycin injection resulted in an apoptotic activity in the photoreceptor, bipolar and ganglion cells. Immunohistochemical analysis suggested that doses of 0.75 mg and 1.5 mg azithromycin, administered intravitreally might be toxic to the newborn rabbit retina.