Monika Modrzejewska

Circulating Stem Cell Populations in Preterm Infants: Implications for the Development of Retinopathy of Prematurity

OBJECTIVE To investigate the association among different circulating stem cell (SC) populations, the levels of selected growth factors and chemokines regulating SC migration in the peripheral blood, and the incidence of retinopathy of prematurity (ROP). METHODS We evaluated 88 participants in this study: 29 preterm infants with ROP, 29 preterm infants without ROP, and 30 healthy full-term infants. Peripheral blood samples collected 10 weeks after delivery were analyzed using flow cytometry, immunofluorescence, real-time reverse transcriptase-polymerase chain reaction, and enzyme-linked immunosorbent assay. The following cell populations were analyzed: (1) lin⁻CXCR4(+)CD45⁻ (enriched in very small embryonic-like SCs), (2) lin⁻CXCR4(+)CD45(+) (enriched in hematopoietic SCs), and (3) CD34(+)CD133(+)CD144(+) (early endothelial progenitor cells) [lin indicates lineage]. The concentrations of vascular endothelial growth factor, basic fibroblast growth factor, hepatocyte growth factor, and stromal cell-derived factor 1 were measured in the plasma. RESULTS The very small embryonic-like SCs and early endothelial progenitor cells expressing neural and endothelial markers were significantly increased in the preterm infants. The number of early endothelial progenitor cells in the peripheral blood was significantly greater in the preterm infants with ROP than in the preterm infants without ROP. An accompanying increase in the concentrations of vascular endothelial growth factor and hepatocyte growth factor was found in the peripheral blood of the preterm infants with ROP. No significant associations were found between hematopoietic SCs and ROP or prematurity. CONCLUSIONS The increased number of early endothelial progenitor cells along with elevated levels of vascular endothelial growth factor and hepatocyte growth factor in preterm infants with ROP suggest that circulating vasculogenic factors may play a role in the development and progression of ROP. The increased number of very small embryonic-like SCs in preterm infants suggests that the development of immature tissues and organs, including the retina, may require a contribution of circulating SCs.

Refractive status and ocular axial length in preterm infants without retinopathy of prematurity with regard to birth weight and gestational age.

Abstract Purpose: To obtain ultrasonographic measurements of ocular axial length (AL) in preterm infants without retinopathy of prematurity (ROP) but with different refractive power in regard to birth weight (BW) and gestational age (GA). Methods: Refraction was measured after cycloplegia (at 6 months of life) in 350 eyes of 180 preterm (non-astigmatic) infants without ROP. Subjects were grouped according to the refractive error: A [above –6.0 dioptres (D)]; B (–3.1 to –6.0 D); C (0 to –3.0 D); D (0.1 to +3.0 D); E (+3.1 to +6.0 D); F (above +6.0 D). The AL measurement was performed by ocular A-scan ultrasound biometry (10 MHz probe). Results: The longest AL was found in group B (20.62 mm) compared to group D and E (19.35, 19.28 mm; P≤0.01) and group F and A (19.63, 19.39 mm; P≤0.05). Only regressive correction for BW was statistically significant. Correlations between AL and BW (Rs=0.23) or GA (Rs=0.17) were found only in group E. Conclusions: AL of myopic eyes was significantly longer. In general, hyperopia was positively correlated with BW, whereas correlation between myopia and BW or GA was not found.

Ocular manifestation of congenital toxoplasmosis, clinical implication – case report

The aim of this case report was to present extremely severe, ophthalmic complications in form of rare, congenital toxoplasmatic bilateral defect of eye-balls concomitant with advanced uveitis, microphthalmia and eye-multistructural developmental abnormalities leading to irreversible visual disability. The ocular diagnosis was confirmed in Ret-Cam II and ultrasonography and it was accompanied with congenital multiorgan lesions including hepato-splenomegaly, thrombocytopenia, leukomalacia, hydrocephalus and ventriculomegaly with neurological symptoms. Serology, PCR of cerebro-spinal fluid and cord blood confirmed the presence of congenital Toxoplasma gondii infection in the infant. The authors took the effort of insightful analysis for the causes of applied treatment failure in mother during pregnancy, analyzing the inefficacy of Spiromycin therapy in pregnant woman and evaluating false-negative result of amniocentesis for Toxoplasma gondii presence. Among many issues concerning anti-toxoplasmatic treatment in mother and infant presented in this article, the need for multiple repetition of toxoplasmatic tests should be underlined including amniotic fluid PCR and ultrasonography which can add much important data for correct diagnosis. The authors indicate that the lack of benefits from conservative therapy in case of suspected Toxopalsma gondii suggestion lead to dramatic multiorgan complications, especially ophthalmo-neurologic, leading to irreversible visual disability.

Retrobulbar blood flow and visual organ function disturbance in the course of giant cell arteritis coexisting with optic disc drusen – a case report

The review presented ophthalmologic syndrome connected with visual organ function disorder in giant cell arteritis patient concomitant with optic nerve disc drusen. Diagnostic difficulties were shown in relation to incidence of both similar ophthalmic symptoms as well as interpretation of specialists examinations results (pattern visual evoked potential test, scanning laser polarimetry, and perimetric tests – kinetic and static). Apart from ophthalmic investigations, significant role of radiological examinations was considered, especially color Doppler ultrasonography of retrobulbar circulation – optic artery, central retinal artery, long posterior ciliary arteries. Adequate interpretation of results seems to be crucial to establish scheme and timing of treatment in case of co-occurrence of the abovementioned disorders. In the presented case early implementation of steroid therapy resulted in improvement of blood flow parameters and the regression of ophthalmological complaints. Visual field deficiency in kinetic perimetry, reduced wave amplitude p100 in visual evoked potential test as well as decrease in number of optic nerve fibers in optic nerve disc region in scanning laser polarimetry exam can be diagnostic features in diagnosis of visual impairment in the course of giant cell arteritis and optic nerve disc drusen. Evaluation of blood flow velocity parameters in retrobulbar arteries in color Doppler ultrasonography is the most valuable screening in monitoring ophthalmic dysregulation in presented disorders.

From ophthalmologist to dentist via radiology

Summary Background: The aim of this paper was to analyze the causes of orbital cellulitis in connection with covert dental changes as well as to establish the role of radiological procedures in the final diagnosis and further treatment of such cases. Material/Methods: Thirty-two patients, aged 25–56, 22 women and 10 men were diagnosed and treated between January 2007 and April 2011 at the Pomeranian Medical University in Szczecin. The patients were examined in the infirmary of the ophthalmological department due to unilateral blepharo-oedema, abrupt pain and vision disturbances; in 5 cases, body temperature increased up to 37.8°C was observed. Next, the patients underwent conventional X-ray examinations of the orbit to exclude any foreign bodies in the eyeball, as well as pantomographies to evaluate the dental status. Visible periapical or periodontal changes in dentition were analyzed with intraoral X-rays with the use of DIGORA System 2.1. Changes found in 3 patients on pantomograms and connected with iatrogenic procedures were further evaluated with CT (64 lines and 128 layers) in frontal, sagittal and axial projections. Orbital disorders were also diagnosed by an ophthalmologist and radiologist with Doppler ultrasound (US) examinations. A linear transducer of 7.5–10 MHz to observe the morphology and vascularity of the eyeball was applied. Results: Iatrogenic treatment was the cause of sinusitis and cellulitis in three cases: incorrectly implanted dental implant in one case, root of the 3rd molar pushed into the sinus in the second case, and communication between the maxillary alveolar process and the sinus after extraction in case of the third patient. Asymptomatic periapical osteolysis, periodontal disease or dead teeth were found in all cases. Diagnosis of orbital cellulitis of dental origin was determined on the basis of clinical, radiographic and ultrasound findings. Ophthalmologic and dental treatment was applied simultaneously. Conclusions: Co-operation between ophthalmologists, radiologists and dentists is necessary during the treatment of such orbital diseases.

The role of lipid dysregulation and vascular risk factors in glaucomatous retrobulbar circulation.

The aim of this study was to evaluate selected lipid-related and vascular factors and their effect on retrobulbar hemodynamics in glaucoma. Fifty-six patients with primary open angle glaucoma (POAG) [POAG group; mean age 68.32 years (SD±0.21)] and 54 patients in control group [CG, mean age 68.1 years (SD±5.34)] were examined. Peak systolic velocity, end-diastolic velocity, mean velocity, pulsatility index, and resistive index of the ophthalmic artery, the central retinal artery and the posterior ciliary arteries were measured by Color Doppler Imaging. Selected lipid-related, systemic and local vascular parameters were evaluated. Statistical methods included Shapiro-Wilk, Student-t and Mann-Whitney U tests, and Spearman rank correlations. In POAG group systolic arterial blood pressure, diastolic arterial blood pressure, total cholesterol, low density lipoprotein cholesterol (LDL-ch), and intraocular pressure were significantly higher; while ocular perfusion pressure, high density lipoprotein cholesterol (HDL-ch) and diastolic ocular perfusion pressure were significantly lower (p≤0.05). Color Doppler Imaging confirmed blood flow abnormalities in all investigated arteries. In addition, significant correlations of HDL-ch, LDL-ch and triglycerides (TG) with peak systolic velocity, end-diastolic velocity and mean velocity were found in individual arteries (p≤0.05). Also, significant associations of systolic arterial blood pressure, ocular perfusion pressure, systolic oclular perfusion pressure and diastolic ocular perfusion pressure with peak systolic velocity, end-diastolic velocity, mean velocity and resistive index were revealed in the posterior ciliary arteries (p≤0.05). Dysregulation of lipid-related and vascular factors, as well as statistical correlation between the above and retrobulbar blood flow indices, might imply their role in vasoconstrictive processes during glaucomatous endotheliopathy.

Rapid onset anterior segment complication following diode laser photocoagulation for retinopathy of prematurity: a case report

Laser treatment for retinopathy of prematurity (ROP) has been proven to be beneficial. We present a case of uncommon, progressive anterior eye segment complication treated with diode laser photocoagulation for ROP which subsequently required surgical management. A 1210 g premature infant, born at 28 weeks of gestation, had bilateral stage 3 threshold ROP on his first screening, at 5 weeks of age. Confluent, laser ablation of avascular retina (Iris Medical, OcuLight S) in order to prevent the progression of ROP was applied. On the next ophthalmological examination, only in the right eye, an uncommon complication, not responding to conservative treatment, was noted. It was described as excessive conjunctiva hypertrophy, misdirected toward the center of the cornea. Indispensable surgical excision of hypertrophied conjunctiva was required, yielding a beneficial outcome. Histology revealed the presence of fibrous tissue. Hypertrophy of conjunctiva after diode laser photocoagulation requires surgical removal in order to prevent vision impairment.

EEG, brain maturation, and the development of retinopathy of prematurity.

Objectives: The factors that influence the central nervous system (CNS) development can affect either the retina or the brain cortex. Immaturity of the brain cortex reflects immaturity of the retina and vice versa. The immature retina is more vulnerable than the mature retina, and is therefore more likely to develop retinopathy of prematurity (ROP). The aim of this study was to compare electroencephalographic brain maturity with ROP severity. Methods: Twenty-one prematurely born infants were divided into two groups according to the severity of ROP. The first group included 12 infants with ROP stage 3 or more and the second group included nine infants with ROP stage 2 or less. We have proposed an index of CNS maturity (M) as a percentage of interburst interval elongation compared with the norm using video-electroencephalography (vEEG). Results: The median M value was 1.07 (range = 0.43–4.44) for infants with severe ROP and −0.1 (range = −1.0 to 1.45) for infants with mild or no ROP (p = 0.000948). Conclusions: The study revealed that CNS maturation delay expressed as M value was higher among infants with severe ROP than among infants with mild or no ROP. EEG examination in prematurely born infants may prove to be a useful tool for predicting ROP development.

Parameters characterizing age-dependent retrobulbar circulation in healthy subjects measured by color Doppler ultrasonography.

Abstract Purpose: The aim of this study was to analyze age-related effects influencing retrobulbar blood flow parameters. Materials and Methods: The study enrolled healthy volunteers (162 eyes) with a mean age of 49.64 years (SD ± 17.50). Participants were divided into 5 groups (G1–G5) based on 12-year age spans (means from 25.41 to 73.87 years). Peak systolic velocity (PSV), end diastolic velocity (EDV), mean velocity (MV), pulsatility index (PI) and resistive index (RI) of the ophthalmic (OA), central retinal (CRA) and posterior ciliary arteries (PCAs) were measured by color Doppler ultrasonography (CDU). In addition, systemic blood pressure (BP), ocular perfusion pressure (OPP) and intraocular pressure (IOP) were evaluated. Statistical analysis was performed using the Shapiro–Wilk, Levene’s, Spjotvoll–Stoline and analysis of variance tests (p ≤ 0.05 was considered statistically significant). Results: In the oldest group, significantly lower PSV, EDV in the CRA and PCAs as well as MV in the CRA were confirmed. Significantly increased RI in the OA, CRA and PCAs in regard to age was recorded. Conclusions: CDU has considerable potential for evaluating hemodynamic changes in the retrobulbar circulation in relation to age. Age laboratory standards for a specific CDU device should be established for further analyses of blood flow in ocular diseases of vascular origin.

Early Experience with Diode Laser Combined with Systemic Steroid Therapy for Severe Stages of Retinopathy of Prematurity

Aims: To study the efficacy of diode laser-systemic steroid therapy in extremely and very-low-birth-weight prematures with severe Retinopathy of Prematurity (ROP). Methods: 36 eyes of 18 prematures, mean gestational age 25.67 weeks (SD ± 1.28) and 811, 83 g birth weight (SD ± 299.08) with aggressive-posterior ROP (AP-ROP) and threshold 3 ROP with plus sign and Extraretinal Fibrovascular Proliferation (EFP) were enrolled. Indirect diode laser combined with intravenous course of Dexamethason was applied. Analyzed risk factors were correlated with the same ones received in cohort treated only with laser. Shapiro-Wilk, t-Student, U Mann-Whitney tests were involved in the statistical analysis (significance levels at p<0.05). Results: Favorable anatomical results after mean 11.29 (SD ± 2.29) days of therapy were noted in 32 eyes (88.88% ), ROP 5 developed in four eyes, but this difference was statistically non-significant (p=0.0612). Transient cortisol decreasing, hyperglycemia and partial adrenal fatigue were noted in some babies. During therapy, arterial systolic and diastolic pressures rose (p<0.05; p<0.01), significantly, which were related with severity of ROP, such as, C-reactive protein, erythrocyte and hematocrit, ventilation duration and number of transfusion (p<0.01). Conclusion: Laser-steroid treatment might be additional effective alternative for severe ROP. Short- and long-term complications should be taken into account when starting this type of therapy