Normative data and repeatability for macular ganglion cell layer thickness in healthy Swedish children using swept source optical coherence tomography.

BACKGROUND: Optical coherent tomography (OCT) technology is evolving with improved resolution and accuracy in segmentation between different cell layers in the retina. The ganglion cell layer in the macula region is a window to see what is happening in the visual pathways and a macula OCT is an examination that most children tolerate. This makes updated normative data necessary since variables may differ between different OCT devices and normative data for children is often not presented. The aim of this study was to develop normative data for macular ganglion cell layer thickness in children, measured with swept source OCT, and investigate the repeatability between measurements. METHODS: Healthy Swedish children between 4 and 16 years old, with normal refraction, spherical equivalent mean:1.13 (sd:0.66) dioptre and normal visual acuity Logmar, mean: 0,015 (sd:0,05), were examined with swept source OCT. Macula OCT was performed three times in both eyes and the different retinal layers were evaluated. RESULTS: Fifty-eight children were screened for inclusion. Fifty-five children were included in the study, 24 boys and 31 girls. Mean age was 8.9 years. Results from right eyes was analysed. The mean average thickness of macular ganglion cell layer thickness, retinal nerve fibre layer/ganglion cell layer boundary to inner plexiform layer/inner nuclear layer boundary, was 68.0 µm (sd:4.0, range:58-77). There was no correlation with sex or age. Fifty-three children manage to complete two, and 41 children three acceptable measurement and the mean coefficient of variation was low. CONCLUSION: The ganglion cell layer thickness differs according to which OCT device that is used, and the population examined. This makes normative data essential to accurately interpret results. Swept source OCT of the macula have excellent repeatability and the examination well tolerated in most children making it an investigation useful for diagnosing and following diseases in the optic pathways.

Macular function in preterm children at school age.

PURPOSE: Macular development is a complex process that starts by mid-gestation and continues several years after birth. A preterm birth could affect this development, causing increased thickness in the central macula, but the effect of the macular function remains uncertain. The aim of this study was to investigate the macular function measured with multifocal electroretinography (mfERG), in former preterm children and compare with healthy controls. A second aim was to correlate central macular function with central macular thickness measured with optical coherent tomography (OCT), in the preterm group. METHODS: Fifteen former preterm children born before 32 weeks of gestation were included in the study. MfERG results from 12 children acted as controls. Visual acuity, refraction in cycloplegia and mfERG were carried out in all children, and optical coherent tomography (OCT) was performed in the preterm children. Main outcomes were P1 amplitudes and implicit times for Rings 1-5 and "sum of groups" of the mfERG, and central macula thickness in area A1 measured with OCT. RESULTS: The P1 amplitudes were reduced in Rings 1-5 and "Sum of groups" in the preterm children compared to controls. There were no significant correlation between P1 amplitude or implicit times in Ring 1 and central macular thickness in the preterm group. CONCLUSIONS: Macular function is reduced in former preterm children compared to children born at term. This suggests that the structural changes with a thicker central retina can have an effect on function and may be one, of probably several, explanations for visual dysfunction in preterm children at school age.

Macular function measured by binocular mfERG and compared with macular structure in healthy children.

PURPOSE: To create normative data in children from binocular multifocal ERG (mfERG) recordings and compare results with the macular thickness. METHODS: Forty-nine 5- to 15-year-old healthy, full-term children were examined with Espion Multifocal System, using DTL electrodes. The stimulus matrix consisted of 37 hexagonal elements. Amplitudes, implicit times and response densities (presented in three rings) of the first-order component P1 were analyzed. Measurements of macular thickness were performed with spectral-domain Cirrus OCT. RESULTS: There were no significant differences between right and left eyes regarding mfERG recordings. Median P1 implicit times of Rings 1-3 of the 46 right eyes were 30.0, 30.0 and 30.8 ms and response densities 20.5, 10.9 and 7.6 nV/deg(2), respectively. Implicit time was longer in boys than in girls (p = 0.009, 0.039, 0.005 in Rings 1-3) and was correlated with age (r s = 0.417, 0.316, 0.274 in Rings 1-3). Implicit time in Ring 1 correlated significantly with the inner circle of the OCT measurements (p = 0.014). CONCLUSION: Binocular mfERG with DTL electrodes is a reliable test of the central macular function in children and correlates with macular structure. As previously not shown, there was a significant difference in implicit time between boys and girls.

Central macular morphology and optic nerve fibre layer thickness in young adults born premature and screened for retinopathy of prematurity.

PURPOSE: To investigate central retinal morphology and optic retinal nerve fibre layer (RNFL) in prematurely born young adults and compare to term born controls. MATERIALS AND METHODS: The participants were 59 prematurely born individuals, with a birthweight ≤1.500 g, and 44 term born controls, all 25-29 years of age. Visual acuity (VA) and contrast sensitivity (CS) were assessed. The retinal macular thickness, ganglion cell-inner plexiform layer (GC-IPL) thickness and RNFL thickness were assessed with Cirrus optical coherence tomography (OCT). RESULTS: Central macular thickness was increased (mean 26.7 µm) in prematurely born individuals compared to controls. The macular GC-IPL was thinner (mean 3.84 µm), also when excluding those with previous retinopathy of prematurity (ROP) and those with neurological complications. Gestational age at birth and previous treatment of ROP were risk factors for a thicker macula, however, not for reduced GC-IPL. The average peripapillary RNFL was thinner (mean 4.61 µm) in the prematurely born individuals, also when excluding those with previous ROP and/or neurological complications. Within the prematurely born group, treated ROP was correlated with increased average RNFL. Further, both better VA and CS were associated with thinner optic nerve RNFL and thicker average GC-IPL. CONCLUSION: Macular and optic nerve morphology were influenced by premature birth as assessed with OCT in adult individuals. Gestational age at birth and treatment for ROP seemed to affect central macular thickness, and treated ROP affected the peripapillary RNFL. Thus, retinal sequelae remained in adulthood.

No findings of SARS-CoV-2 in conjunctival swabs from patients at an emergency outpatient ophthalmological healthcare facility in a Swedish county hospital: a cross-sectional study.

BACKGROUND: COVID-19 is caused by SARS-CoV-2. Virus has been found in conjunctiva of hospitalised patients with COVID-19. Conjunctivitis has also been reported as a presenting symptom of disease. OBJECTIVE: The aims of the study were to investigate the prevalence of SARS-CoV-2 in the conjunctiva and throat among patients presenting at the emergency outpatient ophthalmological healthcare facility at a county hospital along with investigating the seroprevalence of SARS-CoV-2 among staff at the department. METHODS AND ANALYSIS: Swabs from conjunctiva and throat of patients were analysed with real-time reverse transcriptase PCR (RT-PCR) for SARS-CoV-2. Blood samples for serological analysis were obtained from staff. A questionnaire was used to investigate symptoms associated with COVID-19 during the last 3 months as well as symptoms for which the patients were seeking ophthalmological healthcare. RESULTS: In total, 68 patients and 70 individuals from the staff were included in the study. Conjunctivitis was observed in 7% of patients. One patient, presenting with reduced visual acuity due to preretinal haemorrhage in the macula, was positive for SARS-CoV-2 in throat swab. Contact tracing was negative. All other RT-PCR tests were negative. Seropositivity for SARS-CoV-2 was found in 4% of staff. CONCLUSIONS: Our study demonstrated low prevalence of SARS-CoV-2 among patients as well as low seroprevalence of SARS-CoV-2 IgG-antibodies among staff at the ophthalmological ward. The risk for contracting COVID-19 at the department was small. Follow-up investigation is planned.

Association of Gastric Bypass Surgery With Risk of Developing Diabetic Retinopathy Among Patients With Obesity and Type 2 Diabetes in Sweden: An Observational Study.

Importance: Knowledge of the incidence and progression of diabetic retinopathy (DR) after gastric bypass surgery (GBP) in patients with obesity and diabetes could guide the management of these patients. Objective: To investigate the incidence of diabetic ocular complications in patients with type 2 diabetes after GBP compared with the incidence of diabetic ocular complications in a matched cohort of patients with obesity and diabetes who have not undergone GBP. Design, Setting, and Participants: Data from 2 nationwide registers in Sweden, the Scandinavian Obesity Surgery Registry and the National Diabetes Register, were used for this cohort study. A total of 5321 patients with diabetes from the Scandinavian Obesity Surgery Registry who had undergone GBP from January 1, 2007, to December 31, 2013, were matched with 5321 patients with diabetes from the National Diabetes Register who had not undergone GBP, based on sex, age, body mass index (BMI), and calendar time (2007-2013). Follow-up data were obtained until December 31, 2015. Statistical analysis was performed from October 5, 2018, to September 30, 2019. Exposure: Gastric bypass surgery. Main Outcomes and Measures: Incidence of new DR and other diabetic ocular complications. Results: The study population consisted of 5321 patients who had undergone GBP (3223 women [60.6%]; mean [SD] age, 49.0 [9.5] years) and 5321 matched controls (3395 women [63.8%]; mean [SD] age, 47.1 [11.5] years). Mean (SD) follow-up was 4.5 (1.6) years. The mean (SD) BMI and hemoglobin A1c concentration at baseline were 42.0 (5.7) and 7.6% (1.5%), respectively, in the GBP group and 40.9 (7.3) and 7.5% (1.5%), respectively, in the control group. The mean (SD) duration of diabetes was 6.8 (6.3) years in the GBP group and 6.4 (6.4) years in the control group. The risk for new DR was reduced in the patients who underwent GBP (hazard ratio, 0.62 [95% CI, 0.49-0.78]; P < .001). The dominant risk factors for development of DR at baseline were diabetes duration, hemoglobin A1c concentration, use of insulin, glomerular filtration rate, and BMI. Conclusions and Relevance: This nationwide matched cohort study suggests that there is a reduced risk of developing new DR associated with GBP, and no evidence of an increased risk of developing DR that threatened sight or required treatment.

The rim area of the optic nerve head, assessed with Heidelberg retina tomography, is smaller in prematurely born children than in children born at term.

PURPOSE: To examine the optic nerve head with Heidelberg tomography (HRT) in prematurely born school-age children and compare them to children born at term. METHODS: Sixty-three 5-16-year-old children born with a gestational age (GA) of ≤32 weeks were included in the study and compared to 54 children of the same age, born at term. In the preterm group, 29 children had had retinopathy of prematurity (ROP) and nine children had neurological complications. The optic nerve head was assessed with HRT. Three measurements were performed, and the different topographic parameters were noted. RESULTS: Rim area of the optic nerve was significantly smaller in prematurely born children than in children born at term. The mean difference was 0.146 mm2 (p = 0.02). No difference between the groups was found regarding disc area or cup area. In the preterm group, both disc and rim areas were reduced with increasing GA. No correlations with birthweight, ROP or neurological complications were found. CONCLUSION: Reduced rim area of the optic nerve head was found in preterm children of school age. Previous ROP or neurological complication did not influence the result, suggesting the preterm birth per se was the reason for the reduction. Establishing whether this finding was caused by disturbed maturation of the optic nerve or by injury of the axons, or a combination of the two, will require further research.

Reduction of Rod and Cone Function in 6.5-Year-Old Children Born Extremely Preterm.

Importance: The function of rods and cones in children born extremely preterm has not yet been fully investigated. Objective: To compare retinal function via full-field electroretinographic (ffERG) recordings in 6.5-year-old children born extremely preterm with children born at term. Design, Setting, and Participants: A subcohort study was conducted from July 1, 2010, to January 15, 2014, of the national Extremely Preterm Infants in Sweden Study, including preterm children (<27 weeks' gestational age) and children born at term, at 6.5 years of age and living in the Uppsala health care region in Sweden. Full-field electroretinography was performed binocularly, using DTL electrodes and electroretinographic (ERG) protocols with flash strengths of 0.009, 0.17, 3.0, and 12.0 candelas (cd)/s/m2, together with 30-Hz flicker and 3.0 cd/s/m2 single-cone flash. Main Outcomes and Measures: The ffERG recordings were analyzed, and their associations with gestational age and retinopathy of prematurity were examined. Results: Adequate ffERG recordings were obtained from 52 preterm children (19 girls and 33 boys; mean [SD] age at examination, 6.6 [0.1] years) and 45 children born at term (22 girls and 23 boys; mean [SD] age at examination, 6.6 [0.1] years). Lower amplitudes of the combined rod and cone responses (the a-wave of the dark-adapted ERG protocol of 3.0 cd/s/m2: mean difference, -48.9 µV [95% CI, -80.0 to -17.9 µV]; P=.003; the a-wave of the dark-adapted ERG protocol of 12.0 cd/s/m2: mean difference, -55.7 µV [95% CI, -92.5 to -18.8 µV]; P = .004), as well as of the isolated cone response (30-Hz flicker ERG: mean difference, -12.1 µV [95% CI, -22.5 to -1.6 µV]; P = .03), were found in the preterm group in comparison with the group born at term. The implicit time of the combined rod and cone responses (the a-wave of the dark-adapted ERG protocol of 12.0 cd/s/m2) was longer (mean difference, 1.2 milliseconds [95% CI, 0.3-2.0 milliseconds]; P = .01) in the preterm group, as were the isolated cone responses (30-Hz flicker ERG: mean difference, 1.2 milliseconds [95% CI, 0.5-1.8 milliseconds]; P < .001), than in the group born at term. No association was found between the ffERG recordings and gestational age or retinopathy of prematurity in the preterm group. Conclusions and Relevance: Both rod function and cone function were reduced in children born extremely preterm when compared with children born at term. There was no association with retinopathy of prematurity in the preterm group, which suggests that being born extremely preterm may be one of the main reasons for a general retinal dysfunction.

Photoreceptor Function in School-Aged Children is Affected by Preterm Birth.

PURPOSE: Prematurely born children have affected visual functions at school age. Optical coherent tomography (OCT) has shown morphological changes in the retina, suggesting a disturbance in normal retinal development in these children. The aim of this study was to examine retinal function with fullfield electroretinogram (ffERG) in school-aged children born prematurely and compare with children born at term. A second aim was to correlate retinal function with visual acuity (VA), gestational age (GA), birth weight, and retinopathy of prematurity (ROP). METHODS: The study group consisted of 35 former preterm children born before GA of 32 weeks. A group of 42 children born at term acted as controls. All children were between 5- and 18-years old. FfERG was performed in both eyes. Best-corrected VA and refraction in cycloplegia was determined. RESULTS: The a-wave of the combined rod/cone responses was significantly reduced in the prematurely-born children compared with children born at term. There was a correlation between reduced a-wave amplitude in the combined rod/cone response and ROP and GA at birth. CONCLUSION: Function of photoreceptors was affected in prematurely born children, possibly also in children without previous ROP. Whether immaturity per se affects the retinal function remains to be elucidated. TRANSLATIONAL RELEVANCE: The present study illustrates that electrophysiological studies of the retinal function can help us understand visual dysfunctions in prematurely born children.

'Congenital' nystagmus may hide various ophthalmic diagnoses.

PURPOSE: To investigate whether patients registered at a low-vision centre with 'nystagmus' had any underlying, but so far unknown, ophthalmic diagnosis. METHODS: All patients registered at the low-vision centre of Uppsala county with nystagmus as their major diagnosis were identified. Their medical records were studied to exclude those with other general diagnoses that could explain the nystagmus. The remaining group of patients underwent an ophthalmic examination, refraction and optical coherence tomography (OCT). Electroretinogram and genetic analyses were performed when indicated. RESULTS: Sixty-two patients with nystagmus as their main diagnosis were registered at the low-vision centre, Uppsala, and 43 of them had a major diagnosis other than nystagmus. Nystagmus was the major diagnosis in 19 patients, 15 of whom, aged 6-76 years, participated in the study. Two of the patients had foveal hypoplasia and albinism, four a seemingly isolated foveal hypoplasia, three achromatopsia, one rod-cone dystrophy, one degenerative high myopia, and two could not be evaluated. Only two patients appeared to have 'congenital' nystagmus. Eleven of the patients underwent a comprehensive genetic investigation of the PAX 6 gene. In addition, four of the patients were analysed for mutations in FOXC1 and PITX2 and one in FRMD7. No mutations were found in any of the patients analysed. CONCLUSION: The study illustrates that many patients in our study group with nystagmus had underlying ophthalmic diagnoses. Early diagnosis is important to facilitate habilitation and to provide genetic counselling and, in the future, possibly also gene therapy.

Time to consider a new treatment protocol for aggressive posterior retinopathy of prematurity?

PURPOSE: To discuss treatment modalities for aggressive posterior retinopathy of prematurity (AP-ROP). METHODS: The medical charts of all infants with AP-ROP at Uppsala University Hospital, Sweden, during a 2-year period (2009 and 2010) were reviewed. Eight infants (16 eyes) with a mean gestational age of 23.8 weeks and a mean birth weight of 592 g were treated with laser and/or intravitreal injections of bevacizumab (0.4 and 0.625 mg). RetCam photography was used to document the retinal appearance before and after treatment. RESULTS: All infants (16 eyes) had AP-ROP in zone I. Mean time at initial treatment was 34 weeks postmenstrual age. Two eyes (one infant) were only treated with laser, and six eyes (three infants) were treated with laser therapy or cryopexy and, because of lack of regression, with bevacizumab as salvage therapy. Eight eyes (four infants) were treated with a first-line bevacizumab injection and four of these eyes (two infants) with additional laser ablation for continued disease progression in zone II. Macular dragging occurred in one eye of one infant primarily treated with laser. CONCLUSIONS: Given the high complication rate of the extensive laser treatment for zone I ROP, it is worth considering anti-vascular endothelial growth factor treatment as an alternative therapy. Further knowledge concerning side effects and long-term ocular and systemic outcome is warranted before this drug becomes general clinical practice.

Retinal nerve fibre layer thickness in school-aged prematurely-born children compared to children born at term.

AIM: To investigate the retinal nerve fibre layer (RNFL) with optical coherent tomography (OCT) in prematurely-born children. METHODS: 62 children born with a gestational age of ≤32 weeks, and a control group of 54 children born at term with normal birth weight (BW) were included in the study. 28 of the preterm children had retinopathy of prematurity (ROP) in the neonatal period; eight of them had severe ROP (stages 3-4). RNFL thickness was measured with Stratus OCT 3. Mean age at examination was 8.6 years in the preterm children and 10.1 years in the control group. RESULTS: There was a significant difference between the children born preterm and those born at term, regarding RNFL thickness in the superior (right eye (RE), p=0.043; left eye (LE), p=0.048) and the nasal quadrants (RE, p=0.006; LE, p<0.001), as well as average RNFL thickness (RE, p=0.016; LE, p=0.029). This difference was caused by the thinner RNFL in children with previous severe ROP (stages 3 and 4). Within the preterm group, the average RNFL thickness increased with larger BW (RE, p=0.050; LE, p=0.028), but there was no correlation with gestational age at birth. CONCLUSION: The RNFL was reduced in prematurely-born children with severe ROP when compared to children born at term. It is hypothesised that severe retinopathy as well as ablation of the retina with laser treatment or cryotherapy may affect the axons of the ganglion cells and thus reduce RNFL thickness. Prematurely-born children with low BW had a thinner RNFL, suggesting a negative effect of low birth weight on neural development.

Central macular thickness is correlated with gestational age at birth in prematurely born children.

BACKGROUND/AIM: Previous studies have revealed various subnormal visual functions in prematurely born children. The present study aimed to determine the retinal macular thickness in prematurely born children and compare with children born at term. METHODS: The eyes of 65 prematurely born children aged 5-16 years were examined with Stratus optical coherence tomography (OCT) 3, and the results were compared with those of 55 children born at term. The retinal macular thickness in the nine EDTRS macular areas (A1-A9), the foveal minimum and the total macular volume were determined. RESULTS: The central macular thickness (A1 and foveal minimum) was significantly thicker in the prematurely born children than in those born at term. There was no correlation between macular thickness and visual acuity or refraction. Children with previous retinopathy of prematurity (ROP) had significantly thicker central maculae than those without it. Prematurely born children without previous ROP had significantly thicker central maculae than the control group. Multiple regression analyses showed that gestational age at birth was the only risk factor for a thick central macula. CONCLUSION: Prematurely born children had thicker central maculae than those born at term. Regardless of ROP, the degree of prematurity was the most important risk factor for abnormal foveal development.