Gokhan Celik

Comparison of Bevacizumab, Ranibizumab, and Laser Photocoagulation in the Treatment of Retinopathy of Prematurity in Turkey

ABSTRACT Purpose: To evaluate the efficacies and treatment outcomes following intravitreal bevacizumab (IVB), intravitreal ranibizumab (IVR), and laser photocoagulation (LPC) in retinopathy of prematurity (ROP). Methods: This was a retrospective interventional case series study including the data of 134 infants (264 eyes) who were treated with IVB, IVR, or LPC for ROP. The data were collected from two major ROP treatment centers in Turkey without any randomization or masking. Regression of ROP, recurrence profile, complications after each treatment modality, and indications for retreatment were evaluated. The main outcome measures included the total inactivation of ROP with anatomic and refractive outcomes at 1.5 years of adjusted age. Results: There were 55 infants (41.1%) in the IVB group, 22 infants (16.4%) in the IVR group, and 57 infants (42.5%) in the LPC group. All but 3 infants (5.5%) in the IVB group and 11 infants (50%) in the IVR group showed recurrence to stage 1 and 2 ROP following IVB and IVR (p < 0.001). Retreatment was performed in three infants in both IVB and IVR groups (p = 0.098). At 1.5 years of adjusted age, all infants showed favorable anatomic outcome except one infant in the LPC group. No significant difference of the mean spherical equivalent (SE) was observed between the groups (p = 0.131). In Zone I ROP, laser treated infants had significantly higher rates of myopia and high myopia than IVB and IVR treated infants (p = 0.040 and p = 0.019, respectively). Conclusions: Both IVB and IVR treated infants had significantly better refractive outcomes in Zone I ROP as compared to LPC treated infants at 1.5 years of adjusted age. The higher rate of disease recurrence was associated with IVR. Gestational age (GA) and the zone of ROP were also predictive factors for recurrence of ROP in the study.

Evaluation of 2-year outcomes following intravitreal bevacizumab (IVB) for aggressive posterior retinopathy of prematurity.

PURPOSE To evaluate 2-year outcomes following intravitreal bevacizumab (IVB) as monotherapy for aggressive posterior retinopathy of prematurity (APROP). METHODS Medical records of 40 infants were retrospectively reviewed. Group I included infants who had received IVB injections for APROP. Group II included infants who underwent laser treatment for APROP. Anatomic and refractive outcomes and the presence of anisometropia and strabismus were assessed at follow-up examinations. RESULTS Group I included 48 eyes of 25 infants (11 males) with a mean gestational age (GA) of 26.40 ± 1.82 weeks and a mean birth weight (BW) of 901.40 ± 304.60 g. Group II included 30 eyes of 15 infants (6 males) with a mean GA of 27.30 ± 1.82 weeks and a mean BW of 941.00 ± 282.48 g. GA, BW, and gender distributions were similar between groups (P=0.187, P=0.685, and P=1.000, respectively). Refractive errors were significantly less myopic in group I (0.42 ± 3.42 D) than in group II (-6.66 ± 4.96 D) at 2 years (P=0.001). Significantly higher rates of anisometropia and strabismus were observed in group II than in group I (P=0.009 and P=0.036, respectively). CONCLUSIONS The study demonstrated that IVB monotherapy can be useful in the treatment of APROP. The decreased incidence of early unfavorable refractive and functional outcomes in the IVB group compared with the laser group showed a potential benefit for patients treated with IVB, and this needs to be better evaluated in future prospective studies.

Evaluation of the tear film instability in children with allergic diseases

Abstract Context: The presence of dry eye syndrome (DES) in ocular allergic diseases was evaluated in several studies. Despite this, little exists about the tear film instability in atopic children including patients with allergic rhinitis (AR), allergic conjunctivitis (AC) and asthma. This is a study which presents intriguing findings regarding the relationship of tear film instability with clinical aspects in atopic children. Objective: To determine the tear film instability in children with AR, AC and asthma. Materials and methods: One hundred and thirty-five consecutive children with AR, AC and asthma as study group and 45 children without any systemic and ocular abnormality as control group were included in the study. Skin prick tests, measurement of tear film breakup time (TFBUT), serum immunoglobulin E and eosinophil counts were performed in all patients. Also four subgroups of patients were designated as AR group (Group I), AC group (Group II), asthma group (Group III) and control group (Group IV). Results: Socio-demographic characteristics were similar except for family atopy between the groups (p > 0.05). The mean TFBUT was significantly lower in the study group (15.5 ± 4.4 s) than the control group (18.4 ± 2.9 s; p = 0.000). Also, there was no significant differences in the percentage of the patients who has TFBUT<10 s (p = 0.066). In logistic regression analysis, atopy was found to be the determinant of lower TFBUT (OR = 16.33, 95%; CI = 1.17 to 228.05, p = 0.03). Conclusion: The presence of tear film instability was higher in children with AC, AR and asthma. This finding should be taken in consideration in atopic children.

Evaluation of Refractive Errors and Ocular Biometric Outcomes after Intravitreal Bevacizumab for Retinopathy of Prematurity

ABSTRACT Purpose: To assess ocular biometric outcomes following intravitreal bevacizumab (IVB) monotherapy for retinopathy of prematurity (ROP) and compare these results with those of laser photocoagulated infants and with the ones with spontaneously regressed ROP. Materials and methods: Premature infants including those who underwent IVB monotherapy (Group 1) or laser photocoagulation (Group 2) for ROP and infants with spontaneously regressed ROP (Group 3) were recruited for the study. Refractive errors and ocular biometric parameters (Axial length [AL], anterior chamber depth [ACD], and lens thickness [LT]) were measured at adjusted 1 year of age in all subjects. Results: There was no significant difference of spherical equivalent (SE) value between the groups (P = 0.781). The incidence of high myopia was 7.4% in Group 1 and 12.7% in Group 2 (P = 0.081). No infants exhibited high myopia in Group 3. LT was greater in Group 2 when compared to Group 1 and Group 3 (P = 0.011). Lower SE was significantly correlated to longer AL in Group 1 (r = −0.656, P = 0.015). There was a significant positive correlation between SE and ACD values in Group 2 (r = 0.391, P = 0.005). Conclusion: The study showed no significant difference of SE between the groups. High myopia was only present among the treated infants either with IVB or laser. Infants who received laser treatment significantly had thicker lenses.

Effect of Single Intravitreal Bevacizumab on Ophthalmic and Middle Cerebral Arterial Blood Flow in Retinopathy of Prematurity

Purpose: To evaluate the effect of a single intravitreal bevacizumab (IVB) injection on blood flow parameters in the ophthalmic artery (OA) and middle cerebral artery (MCA) in infants with retinopathy of prematurity (ROP). Materials and Methods: This prospective and interventional study included 15 infants with ROP who were treated with IVB. Peak systolic velocity (PSV), end-diastolic velocity, mean velocity (MV) and resistivity index were measured using pulse wave Doppler ultrasonography (Philips En Visor C, Amsterdam, The Netherlands) in the OA and MCA, before IVB injection and 1 day, 1 week and 1 month after IVB injection. Results: Measurements of PSV-OA, MV-OA and PSV-MCA showed significant changes after IVB treatment (p = 0.01, p = 0.02, p = 0.02, respectively). The PSV-OA measurements at 1 week and 1 month were significantly lower than the baseline PSV-OA measurement (p = 0.03 and p = 0.01, respectively). The MV-OA measurement was significantly lower at 1 month following IVB as compared to the baseline MV-OA measurement (p = 0.03). The PSV-MCA showed a significant decline 1 day after IVB injection (p = 0.03). Conclusions: The study demonstrated that IVB causes significant alterations in blood flow parameters in the OA and MCA predicted by Doppler ultrasonography in infants with ROP.

Central corneal thickness measurements in premature infants.

AIM To evaluate the central corneal thickness (CCT) measurements of premature infants. METHODS The premature infants who were born between 25-34wk of gestational age (GA) were retrieved for the study. All CCT measurements were performed within the first 2d of their life under topical anesthesia by using an ultrasonic pachymeter. RESULTS The mean CCT of 200 eyes was 647.79±63.94 µm. The mean CCT of the right and left eyes were similar (647.30±64.72 µm and 648.29±63.47 µm consecutively). The mean CCT of the girls was 642.08±54.89 µm and the boys was 653.07±71.14 µm, with no statistically significant difference (P>0.05). But there was a negative correlation of the CCT with GA and birth weight (BW) (P<0.01). CONCLUSION The CCT values of premature babies were negatively correlated with GA and BW.

Characteristics of Severe Retinopathy of Prematurity in Infants with Birth Weight above 1500 Grams at a Referral Center in Turkey

Purpose To demonstrate the clinical characteristics and treatment outcomes of severe retinopathy of prematurity (ROP) in preterm infants with birth weight (BW) above 1500 g in Turkey. Methods A retrospective review of 5920 ROP records was performed in Zeynep Kamil Maternity and Children’s Diseases Training and Research Hospital. The records were obtained from ROP treatment center of the same institute between 2011 and 2016. The data comprised the demographic and clinical characteristics including, gestational age, BW, systemic risk factors, zone and stage of ROP, ROP type, treatment modality, treatment outcomes and inborn/outborn status of the babies. Results A total of 36 infants (71 eyes) with severe ROP and BW> 1500 g were retrieved. There were 30 infants (83.3%) with type 1 ROP and 6 infants (16.7%) with aggressive posterior ROP (APROP). 3 infants (8.3%) were born at our hospital whereas 33 (91.7%) were referred from outer private neonatal intensive care unit (NICU) centers. Zone I APROP was detected during the initial screening. 21 infants (58.3%) underwent laser treatment while 15 (41.7%) received intravitreal bevacizumab (IVB) injections. No unfavorable structural outcome was observed following either treatment modality. Conclusion Severe ROP may occur in heavier preterm infants. Laser treatment and IVB injections were useful in selected cases. Presence of APROP at first examination suggests an earlier screening in heavier babies. Standardization of private NICU centers as well as establishing a national ROP protocol is necessary in Turkey.

Evaluation of Factor V Leiden, Prothrombin G20210A, MTHFR C677T and MTHFR A1298C gene polymorphisms in retinopathy of prematurity in a Turkish cohort.

ABSTRACT Background: To assess Factor V Leiden (FVL) (rs6025), Prothrombin G20210A (rs1799963), MTHFR C677T (rs1801133), and MTHFR A1298C (rs1801131) gene mutations as risk factors in the development of retinopathy of prematurity (ROP). Materials and methods: A total of 105 children were included in this cross-sectional study. Patients were divided into two groups. The study group consisted of 55 infants with a history of ROP and the control group comprised 50 healthy infants with term birth. All subjects were screened for the presence of certain mutations (FVL, Prothrombin G20210A, MTHFR C677T and MTHFR A1298C) by Real-Time PCR at 1 year of age. Results: The mean gestational age (GA) and birth weight (BW) of the study group were, 28.65 ± 2.85 weeks and 1171 ± 385.74 g, respectively. There were no significant differences of genotype and allele frequency of Prothrombin G20210A, MTHFR A1298C and MTHFR C677T between the study and control groups (p > 0.05). Eight children (14.5 %) had heterozygous and one child (1.8%) had homozygous FVL mutation in the study group. One child (2%) in the control group had heterozygous FVL mutation. There was statistically significant differences of FVL allele and genotype frequencies between the groups (p < 0.05). Conclusions: The prevalence of FVL polymorphism (16.3 %) was higher in ROP patients than control subjects in this Turkish cohort. We suggest a possible association of FVL mutation with ROP at the end of the study.

Effect of laser photocoagulation on plasma levels of VEGF-A, VEGFR-2, and Tie2 in infants with retinopathy of prematurity

PURPOSE To report the baseline plasma levels of vascular endothelial growth factor-A (VEGF-A), soluble vascular endothelial growth factor receptor-2 (sVEGFR-2) and soluble Tie2 in infants with treatment-requiring retinopathy of prematurity (ROP) and to investigate the effect of laser treatment on the plasma levels. METHODS Blood samples were collected from infants with prethreshold type 1 ROP before, 1 day after, and 1 week after confluent laser photocoagulation. Enzyme-linked immunosorbent assay procedure was used to determine plasma VEGF-A, sVEGFR-2, and sTie2 levels. RESULTS A total of 48 eyes of 30 infants were included. The mean postconceptional age at which laser photocoagulation was performed was 37.5 ± 2.9 weeks. The mean number of laser spots applied to each eye was 1,480 ± 420. Regression of active retinopathy occurred within 1 week of treatment in all cases. Baseline plasma VEGF-A, sVEGFR-2, and sTie2 levels did not differ between unilateral and bilateral and also zone I and zone II disease. A significantly progressive decrease was observed in plasma VEGF-A, sVEGFR-2, and sTie2 levels at 1 day and 1 week after laser photocoagulation. CONCLUSIONS Plasma levels of VEGF-A, sVEGFR-2, and sTie2 decreased significantly in our patients after laser treatment; however, because of the variability in the measurements, further studies evaluating the clinical value of these angiogenic factors in patients with treatment-requiring ROP are necessary.

Ocular Surface Characteristics in Diabetic Children

ABSTRACT Purpose: To compare tear film osmolarity (TFO) and other dry eye tests between diabetic children and normal healthy children. Materials and Methods: Twenty-six diabetic children (Group 1) and 20 healthy children without any ocular and/or systemic disorder (Group 2) were enrolled in the study. Detailed ocular surface assessment including, ocular surface disease index (OSDI) questionnaire, TFO measurement (Tear Lab Osmolarity System, San Diago, CA, USA), corneal epithelial thickness (CET) measurement using the anterior segment optical coherence tomography (OCT) (RTVue CAM, Optovue Inc, CA, USA), tear film break-up time (TFBUT) test, Schirmer test, meibography, and conjunctival brush cytology were performed. The results were compared between the groups. Results: The mean TFO was significantly higher in Group 1 (328.8 ± 12.8) than Group 2 (313.6 ± 15.1) (p = 0.001). The mean Schirmer test score was significantly lower in Group 1 (16.7 ± 5.1) than Group 2 (23.6 ± 5.6) (p = 0.00). Cytologic analysis revealed grade 0 changes in 11 patients (42.3%), grade 1 changes in 13 patients (50%), and grade 2 changes in 2 patients (7.7%) in Group 1 whereas grade 0 changes in 18 patients (90%) and grade 1 changes in 2 patients (10%) were observed in Group 2 (p = 0.004). The TFO levels were significantly associated with HbA1c levels (r = 0.459, p = 0.018). Conclusion: The study revealed significantly higher TFO, lower Schirmer test scores and changes in conjunctival cytology in diabetic children. Altered ocular surface changes in diabetic children may be due to the result of increased TFO.