Case control study of risk factors and ophthalmological outcomes of very low birth weight infants with Type 1 retinopathy of prematurity.

INTRODUCTION: We evaluated the risk factors associated with Type 1 retinopathy of prematurity (ROP) in very low birth weight (VLBW) infants and compared ophthalmologic outcomes between cases with Type 1 ROP who received treatment and gestational age-matched controls with mild or no ROP not requiring treatment. METHODS: This was a retrospective case-control study of VLBW infants born in National University Hospital, Singapore, from January 2001 to December 2013. 17 cases with Type 1 ROP were each matched for gestational age with controls who had either mild (below Stage 2) or no ROP. Antenatal, perinatal and postnatal variables, as well as childhood ophthalmologic outcomes, were collected from their clinical records and analysed. RESULTS: The number of packed cell transfusions and highest fraction of inspired oxygen given at weeks 7-10 were found to be statistically significant on multivariate analysis (p = 0.045 and p = 0.049, respectively). None of the infants had blindness or retinal detachment, and there were no significant differences in refractive errors between the groups at 1-4 years of age. Strabismus at four years of age was more common in the group with Type 1 ROP (p = 0.023). CONCLUSION: Increased episodes of blood transfusions and chronic lung disease requiring high oxygen supplementation at 7-10 weeks of life are significant risk factors associated with Type 1 ROP in VLBW infants in our study. Strabismus at four years is more common in this group of patients. This study highlights the importance of long-term ophthalmologic surveillance for these high-risk children.

HOXA9 is a novel myopia risk gene.

PURPOSE: A recent meta-analysis revealed PAX6 as a risk gene for myopia. There is a link between PAX6 and HOXA9. Furthermore, HOXA9 has been reported to activate TGF-ß that is a risk factor for myopia. We speculate HOXA9 may participate in myopia development. METHODS: The Singapore GUSTO birth cohort provides data on children's cycloplegic refraction measured at age of 3 years and their methylation profile based on the umbilical cord DNA. The HOXA9 expression levels were measured in the eyes of mono-ocular form deprivation myopia in mice. The plasmid with the mouse HOXA9 cDNA was constructed and then transfected to mouse primary retinal pigment epithelial (RPE) cells. The expression levels of myopia-related genes and cell proliferation were measured in the HOXA9-overexpressed RPE cells. RESULTS: A total of 519 children had data on methylation profile and cycloplegic refraction. The mean spherical equivalent refraction (SE) was 0.90D. Among 8 SE outliers (worse than -2D), 7 children had HOXA9 hypomethylation. The HOXA9 levels in the retina of myopic eyes was 2.65-fold (p = 0.029; paired t-test) higher than the uncovered fellow eyes. When HOXA9 was over-expressed in the RPE cells, TGF-ß, MMP2, FGF2 and IGF1R expression levels were dose-dependently increased by HOXA9. However, over-expression of HOXA9 had no significant influence on IGF1 or HGF expression. In addition, HOXA9 also increased RPE proliferation. CONCLUSION: Based on the human, animal and cellular data, the transcription factor HOXA9 may promote the expression of pro-myopia genes and RPE proliferation, which eventually contribute to myopia development.

Macular Ganglion Cell and Retinal Nerve Fiber Layer Thickness in Children With Refractive Errors-An Optical Coherence Tomography Study.

PURPOSE: To study the distribution of macular ganglion cell-inner plexiform layer (GC-IPL) thickness and peripapillary retinal nerve fiber layer (RNFL) thickness in children with refractive errors. MATERIALS AND METHODS: Two hundred forty-three healthy eyes from 139 children with refractive error ranging from -10.00 to +5.00 D were recruited from the National University Hospital Eye Surgery outpatient clinic. After a comprehensive ocular examination, refraction, and axial length (AL) measurement (IOLMaster), macular GC-IPL and RNFL thickness values were obtained with a spectral domain Cirrus high definition optical coherence tomography system (Carl Zeiss Meditec Inc.). Only scans with signal strength of >6/10 were included. Correlation between variables was calculated using the Pearson correlation coefficient. A multivariate analysis using mixed models was done to adjust for confounders. RESULTS: The mean spherical equivalent refraction was -3.20±3.51 D and mean AL was 24.39±1.72 mm. Average, minimum, superior, and inferior GC-IPL were 82.59±6.29, 77.17±9.65, 83.68±6.96, and 81.64±6.70 µm, respectively. Average, superior, and inferior peripapillary RNFL were 99.00±11.45, 123.20±25.81, and 124.24±22.23 µm, respectively. Average, superior, and inferior GC-IPL were correlated with AL (ß=-2.056, P-value 0.000; ß=-2.383, P-value 0.000; ß=-1.721, P-value 0.000), but minimum GC-IPL was not (ß=-1.056, P-value 0.115). None of the RNFL parameters were correlated with AL. CONCLUSIONS: This study establishes normative macular GC-IPL and RNFL thickness in children with refractive errors. Our results suggest that high definition optical coherence tomography RNFL parameters and minimum GC-IPL are not affected by AL or myopia in children, and therefore warrants further evaluation in pediatric glaucoma patients.

Is there a link between passive smoke exposure and early-onset myopia in preschool Asian children?

PURPOSE: To investigate the association of passive tobacco smoke exposure with early-onset myopia among three-year-old children in Singapore. METHODS: Pregnant mothers who attended their first trimester clinic at two major maternity units were recruited into the GUSTO birth cohort. The current analysis comprised 572 three-year-old children, who underwent cycloplegic autorefraction and axial length (AL) measurements. Myopia was defined as spherical equivalent (SE) of ≤-0.50 dioptres (D). Either parent completed questionnaires describing their child's exposure to passive smoke at six months, one and two years of age. RESULTS: There were 197 children (36.2%) who were exposed to passive smoke from birth to before six months. Compared to non-exposed children, children exposed to any passive smoke from birth to before six months experienced greater myopia prevalence (adjusted OR = 2.79; 95% CI: 1.24-6.29; p = 0.01). The odds of myopia in a child was greater if a smoker smokes at home, in the family car, or in the presence of the child (adjusted OR = 3.95; 95% CI: 1.41-11.09; p < 0.01) compared to non-exposed child. In contrast to myopia, childhood exposure to passive smoke did not systematically shift mean values for SE or AL. CONCLUSIONS: In this prospective birth cohort study, we found that childhood exposure to passive smoke from birth to before six months slightly increased the risk of early-onset myopia. This may indicate a delayed response to passive smoke exposure before six months and the development of myopia at three years of age. Our study is limited by the small number of myopic children at this young age. Thus, larger prospective studies using more objective cotinine level measures are required to fully establish and understand the influence of tobacco smoke on refractive development in older children.

The accuracy of anterior segment optical coherence tomography (AS-OCT) in localizing extraocular rectus muscles insertions.

PURPOSE: To evaluate the accuracy of the anterior segment optical coherence tomography (AS-OCT) in measuring the distance from the limbus to the insertion of primary and previously operated rectus muscles in children. METHODS: In this prospective, double masked, observational study the distance of the extraocular muscle insertion from the limbus measured by AS-OCT preoperatively was compared to intraoperative measurement using the surgical calipers. Consecutive patients 4-18 years of age undergoing primary or repeat strabismus surgery on horizontal or vertical rectus muscles between September 2013 and May 2014 were included. Patients with any condition that interfered with imaging were excluded. Participants were asked to look in the direction opposite to the muscle to ensure that the middle third of the muscle was being imaged and measured. RESULTS: A total of 65 muscles were evaluated, including 9 muscles undergoing reoperation and 10 vertical rectus muscles. Of these, 62 muscles were successfully imaged. In all reoperated eyes, the AS-OCT measurements were within 1 mm of the intraoperative measurements. Overall, 89.7% (95% CI, 78.8%-96.1%) of the measurements were within the 1 mm difference considered "clinically acceptable." The intraclass correlation coefficient comparing the reliability of the AS-OCT measurements with intraoperative measurements was 0.73 (95% CI, 0.53-0.85), or "good" agreement. CONCLUSIONS: AS-OCT can accurately detect rectus muscle insertions in primary or previously operated cases in children as young as 4 years of age.

Cyclic strabismus in adults.

Cyclic strabismus is a rare condition that usually occurs in children and is characterized by alternating intervals of straight and strabismic eyes. In adults with the condition, strabismus surgery often eliminates the cycles. We report a case of adult-onset cyclic esotropia that was converted into a cyclic exotropia.

Quantitative assessment of changes in trabeculectomy blebs after laser suture lysis using anterior segment coherence tomography.

PURPOSE: To quantify changes in bleb morphology after laser suture lysis (LSL) using anterior segment optical coherence tomography (AS-OCT). PATIENTS AND METHODS: This was a prospective observational case series of patients who underwent trabeculectomy surgery with mitomycin-C and required subsequent LSL. Subjects were assessed before and immediately after LSL, and at 3 months after LSL. At each visit, a standardized cross-sectional AS-OCT image of the bleb was obtained, from which a masked observer measured bleb height (hB), cavity height (hC), wall cross sectional area (AW), cavity cross sectional area (AC), and bleb cross sectional area (AB) using custom software. RESULTS: Twenty-five subjects (25 eyes) were examined. LSL was performed at a mean of 21.5±16.3 days after trabeculectomy. Immediately after LSL, there was a significant increase in mean hB (P=0.026) and mean hC (P=0.45) from pre-LSL. At 3 months after LSL, there was a significant increase in mean hB (P=0.003), mean AC (P=0.047), and mean AB (P=0.006) as compared with before LSL. Increase in hB and hC immediately after LSL was predictive of outcome at month 3. CONCLUSIONS: AS-OCT was able to quantify changes in bleb morphology after LSL, some of which were predictive of eventual outcome.

Visual acuity outcomes with SA60D3, SN60D3, and ZM900 multifocal IOL implantation after phacoemulsification.

PURPOSE: To assess the near and distance visual acuity achieved with implantation of the ReSTOR SA60D3 and SN60D3 (Alcon Laboratories Inc) and Tecnis ZM900 (Abbott Medical Optics [AMO]) multifocal intraocular lens (IOL) after cataract surgery. METHODS: This is a retrospective study of 108 eyes of 54 patients who underwent uneventful bilateral phacoemulsification of cataract and IOL implantation at an ophthalmic center in Singapore by a single surgeon. Inclusion criteria were visually significant cataracts, corneal astigmatism <2.00 diopters, and no other ocular diseases. Patients received the SA60D3, SN60D3, or ZM900 multifocal IOL in both eyes. Binocular near and distance visual acuity outcomes were assessed 3 months after second-eye surgery. RESULTS: No difference in mean postoperative uncorrected and best spectacle-corrected visual acuity for distance among the groups was noted. The ZM900 lens was significantly better than both ReSTOR lenses for uncorrected near vision with 96.7% achieving N5 compared to 75% of SA60D3 patients and 83.3% of SN60D3 patients (P=.003). For distance corrected near vision, 100% of ZM900 patients achieved N5 compared to 83.3% for each the SA60D3 and SN60D3 IOLs (P=.005). No significant difference between both ReSTOR lenses for near vision was noted. CONCLUSIONS: All three IOLs provide similar uncorrected and best corrected distance visual acuity. However, the ZM900 IOL provides better binocular distance corrected and uncorrected near acuity than the SA60D3 or SN60D3. The ZM900 IOL group was more myopic preoperatively compared to the other two groups, which may be a contributing factor.