Comparison of the local effects of different intracameral cefuroxime solutions on rabbit cornea.

PURPOSE: We aimed to compare the local effects of intracameral cefuroxime diluted in normal saline (SF groups) against those of cefuroxime in balanced salt solution (BSS group) on the cornea of rabbits. MATERIALS AND METHODS: Fourteen New Zealand albino rabbits were randomised into two groups. The right eyes of the rabbits in the SF group I were injected intracamerally with 1 mg cefuroxime diluted with 0.1 mL normal saline (n = 7), whereas the right eyes of the BSS group II were injected with 1 mg intracameral cefuroxime diluted with 0.1 mL with balance salt solution, and the left eyes of all rabbits received no treatment group III (control group). Corneal thickness was measured with pachymetry before and 1 week after the injection. Corneal samples were evaluated with light, specular and electron microscopy. RESULTS: Mean endothelial cell count was lower in the SF than in the BSS and control groups. Although an increase in corneal thickness was found in both treatment groups, this was not the case for the control group. The corneal endothelium preserved its hexagonal structure in all groups. Although both treatment groups showed a loss of endothelial microvilli, this was more prevalent in the SF group. However, microvilli were preserved in the control group. Dissolution of tight junctions in corneal endothelium was observed in the SF group only. Mitochondrial swelling, coarsening of endoplasmic reticulum, cytoplasmic vacuolisation, and increased endothelial cell sizes were the same in both treatment groups but was not observed in the control group. Thicker and more oedematous corneal stroma were observed in the SF group compared with the BSS and control groups. CONCLUSION: Dilution of intracameral cefuroxime in BSS yielded superior results compared with dilution in normal saline owing to toxicity to the endothelial cells and decline in the endothelial cell number, resulting in intracellular and intercellular morphological changes. BSS or any other solution with proven safety should be used in clinical studies.

Long-term evaluation of refractive changes in eyes of preterm children: a 6-year follow-up study.

PURPOSE: To investigate the longitudinal changes in refractive errors in preterm children with and without retinopathy of prematurity (ROP) in the first 6 years of life. METHODS: We included 226 preterm children with a gestational age of ≤34 weeks: 222 eyes with no ROP, 73 eyes with mild ROP and 145 eyes with severe ROP. Longitudinal cycloplegic refraction data were collected initially and yearly thereafter until 6 years of age. RESULTS: Eyes in the severe ROP group showed an increase in myopia values between the 1- and 3-year examinations (p = 0.005), with little change thereafter. However, the mild/no ROP group demonstrated a nonsignificant increasing myopia values throughout the 6-year follow-up (p = 0.073). Both the mild/no ROP and severe ROP groups were found to have increasing mean astigmatism values with increasing age, albeit nonsignificantly (p = 0.418, p = 0.384, respectively). Likewise, the stable mean values of anisometropia increased nonsignificantly during the first 6 years of life in both the mild/no ROP and severe ROP groups (p = 0.246, p = 0.073, respectively). Severe ROP group had higher values regarding myopia, astigmatism, and anisometropia parameters than the mild/no ROP group for all ages during the follow-up. CONCLUSIONS: Preterm children with severe ROP should be closely monitored, and also those with mild/no ROP should be carefully followed up for not overlooking possible increases in refractive conditions.

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.

Primary and Secondary Intraocular Lens Implantations in Children With Pediatric Cataract: Visual Acuity and Strabismus at the Age of 2 Years and Older.

PURPOSE: To compare the visual outcomes of primary and secondary intraocular lens (IOL) implantations and to identify the risk factors for the development of strabismus in patients with pediatric cataract. METHODS: The records of the pediatric patients who had undergone cataract surgery between January 1999 and November 2014 were reviewed retrospectively. The results of the cases with cataract extraction with primary IOL implantation (primary group) and cases with secondary IOL implantation (secondary group) were compared and the risk factors for the development of strabismus were investigated. RESULTS: This study included 220 eyes of 148 patients who had surgery for pediatric cataract. The mean age of the patients was 6.84 ± 3.45 years (range: 2 to 17 years) for the primary group at the time of cataract extraction and primary posterior chamber IOL implantation and 8.92 ± 5.12 years (range: 2 to 18 years) for the secondary group at the time of secondary IOL implantation (P = .118). Strabismus developed in 28 patients (23.73%) in the primary group and 9 patients (30%) in the secondary group (P = .702). At the last postoperative examination, Snellen visual acuity was 0.44 and 0.28 for the primary and secondary groups, respectively (P = .013). There was a negative relationship between visual acuity and the development of strabismus (P = .048), whereas there was a positive relationship between the follow-up period and the development of strabismus (P = .008). CONCLUSIONS: Optic rehabilitation of the pediatric cataract is an important factor in the development of strabismus. These cases should be monitored closely. [J Pediatr Ophthalmol Strabismus. 2017;54(2):97-102.].

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.

Associations of VEGF/VEGF-receptor and HGF/c-Met promoter polymorphisms with progression/regression of retinopathy of prematurity.

PURPOSE: To determine the effect(s) of vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2), hepatocyte growth factor (HGF), and HGF receptor (c-Met) polymorphisms on progression/regression of retinopathy of prematurity (ROP) in premature infants. MATERIALS AND METHODS: This study comprised both a prospective analysis and a clinically relevant laboratory investigation. Enrolled were 123 Turkish preterm infants--gestational age (GA), ≤34 weeks; birth weight (BW), ≤1500 g--from a single tertiary care center. Infants were grouped as those who had undergone laser therapy (Group 1, n = 42), those with spontaneously regressed ROP (Group 2, n = 50), and those with no ROP (controls) (Group 3, n = 31). VEGF (-634) C and VEGF (-460) C polymorphisms were analyzed using the PCR-restriction fragment length polymorphism (RFLP) (PCR-RFLP) technique. VEGFR-2, HGF, and c-Met gene promoter polymorphisms were determined by direct sequencing. RESULTS: Mean GAs and BWs of infants in Groups 1 and 2 were statistically significantly lower than those of Group 3 (p = 0.001). Frequencies of VEGF (-634) C and VEGF (-460) C polymorphisms were similar for all groups. We found a +32G→A single-nucleotide polymorphism (SNP) in the promoter region of the VEGFR-2 gene. HGF and c-Met gene promoter polymorphisms were not found in any group. CONCLUSIONS: Our results indicate that there is no association between the carrier states of gene promoter polymorphisms VEGF (-634) C, VEGF (-460) C, and VEGFR-2, and progression or spontaneous regression of ROP in preterm infants. The absence of HGF and c-Met polymorphisms in our study groups suggests that polymorphisms in the minimal promoters of these genes are not involved in the pathogenesis of ROP.

Microdebrider assisted endoscopic marsupialization of congenital intranasal nasolacrimal duct cysts.

OBJECTIVE: To provide information on the clinical characteristics and management of an uncommon congenital nasolacrimal system anomaly, intranasal nasolacrimal duct cyst. METHODS: Three patients treated with microdebrider assisted endoscopic marsupialization for intranasal nasolacrimal duct cysts were included in this study. Management and outcomes are compared to previous reports in the literature. RESULTS: Patients were presented in between 2007 and 2010. Diagnosis was made by clinical observation and endoscopic nasal examination. The first patient is a 1 year old child with congenital dacryocystocele presented as a right medial canthal mass and ipsilateral intranasal cyst. The second patient is a 60 days old child presented with nasal obstruction and feeding difficulty who was found to have bilateral intranasal cystic masses. The third patient was a 6 days old newborn with respiratory distress, whose nasal endoscopy revealed bilateral choanal atresia and left side intranasal cyst. All three cases were treated with nasal endoscopic marsupialization and no recurrence of symptoms and physical findings were found. CONCLUSIONS: Intranasal nasolacrimal duct cysts may lead to nasal obstruction, respiratory distress and feeding difficulty. An otorhinolaryngologist should be consulted, as nasal endoscopy is fundamental for diagnosis. Microdebrider assisted endoscopic marsupialization is a safe and curative treatment.