Association of progressive optic disc tilt with development of retinal nerve fibre layer defect in children with large cup-to-disc ratio

Background/aimsWhereas myopic optic disc deformation has been posited as a risk factor for glaucomatous damage, longitudinal studies evaluating their association have been sparse. We investigated whether the optic nerve head (ONH)’s morphological alteration during myopia progression play any role in development of retinal nerve fibre layer defect (RNFLD) in children with a large vertical cup-to-disc ratio (vCDR).MethodsSixty-five normotensive eyes of 65 children aged under 8 years with (1) vCDR ≥0.5 but no additional signs of glaucoma and (2) who could be tracked at young adulthood (18–28 years) were included. Children’s spherical equivalent (SE), intraocular pressure, vCDR and optic disc tilt ratio were recorded. Rare events logistic regression analysis was employed to identify factors associated with RNFLD-development risk.ResultsThe study group’s mean age was 5.4±1.3 years, its average vCDR was 0.62±0.07, and the average SE was −0.3±1.4 dioptres ((D), range −3.15 to 2.75D) at the baseline. After an average follow-up of 16.1±3.0 years, the mean vCDR was 0.64±0.09, and the mean SE, −3.2±2.2D (range −7.25 to 0.00 D). Among the 65 eyes, 12 (18.5%) developed RNFLD. A greater SE change (OR=1.737, p=0.016) and a greater increase in tilt ratio (OR=2.364, p=0.002) were both significantly associated with higher RNFLD-development risk.ConclusionIn this cohort of Korean children with large vCDR, progressive optic disc tilt in the course of myopia progression was associated with higher RNFLD-development risk. This finding suggests that morphological alterations in the ONH during axial elongation might represent an underlying susceptibility to glaucomatous damage in large-vCDR children.

Clinical Features of the Fellow Eyes of Children with Unilateral Facial Port-Wine Stains and Ipsilateral Glaucoma

Purpose: To investigate the clinical features of non-affected fellow eyes in patients with unilateral facial port-wine stain (PWS) and ipsilateral secondary glaucoma.Methods: We performed a retrospective analysis of the medical records of 35 patients with unilateral facial PWS glaucoma and those of controls (35 subjects without both facial PWS and glaucoma) between September 1996 and May 2020. We noted patients’ age at the glaucoma diagnosis (for unilateral facial PWS glaucoma patients) or at the initial examination (for controls), cup-to-disc ratio (CDR), and intraocular pressure (IOP). We compared the clinical features between the glaucoma-free eyes in patients with unilateral facial PWS glaucoma and the controls.Results: The mean age at the glaucoma diagnosis for unilateral facial PWS glaucoma patients was 0.56 ± 0.99 years (range, 0.08-4). The mean IOP of the glaucoma-free eyes was 16.68 ± 5.73 mmHg (range, 9-22.9), and the mean CDR was 0.37 ± 0.14 (range, 0.15-0.80) at glaucoma diagnosis. The mean IOP of the glaucoma-free eyes was 14.14 ± 6.29 mmHg (range, 8.1-26.7), and the mean CDR was 0.37 ± 0.12 (range, 0.26-0.82) at final examination. When comparing glaucoma-free eyes of the unilateral facial PWS glaucoma patients with the control group (mean age, 11.2 ± 7.4 years), the mean CDR was significantly greater (0.37 ± 0.12 vs. 0.30 ± 0.08; p = 0.014) but there was no significant difference in the mean IOP (14.14 ± 6.29 mmHg vs. 14.57 ± 2.49 mmHg; p = 0.712).Conclusions: The glaucoma-free eyes of unilateral facial PWS glaucoma patients showed greater CDR compared to the non-facial PWS and non-glaucoma controls. Additional longitudinal studies are needed to investigate the clinical course of those eyes, whether the risk of developing glaucoma is increased.

A Precise Method to Evaluate 360 Degree Measures of Optic Cup and Disc Morphology in an African American Cohort and Its Genetic Applications

(1) Background: Vertical cup-to-disc ratio (CDR) is an important measure for evaluating damage to the optic nerve head (ONH) in glaucoma patients. However, this measure often does not fully capture the irregular cupping observed in glaucomatous nerves. We developed and evaluated a method to measure cup-to-disc ratio (CDR) at all 360 degrees of the ONH. (2) Methods: Non-physician graders from the Scheie Reading Center outlined the cup and disc on digital stereo color disc images from African American patients enrolled in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study. After converting the resultant coordinates into polar representation, the CDR at each 360-degree location of the ONH was obtained. We compared grader VCDR values with clinical VCDR values, using Spearman correlation analysis, and validated significant genetic associations with clinical VCDR, using grader VCDR values. (3) Results: Graders delineated outlines of the cup contour and disc boundaries twice in each of 1815 stereo disc images. For both cases and controls, the mean CDR was highest at the horizontal bisector, particularly in the temporal region, as compared to other degree locations. There was a good correlation between grader CDR at the vertical bisector and clinical VCDR (Spearman Correlation OD: r = 0.78 [95% CI: 0.76–0.79]). An SNP in the MPDZ gene, associated with clinical VCDR in a prior genome-wide association study, showed a significant association with grader VCDR (p = 0.01) and grader CDR area ratio (p = 0.02). (4) Conclusions: The CDR of both glaucomatous and non-glaucomatous eyes varies by degree location, with the highest measurements in the temporal region of the eye. This method can be useful for capturing innate eccentric ONH morphology, tracking disease progression, and identifying genetic associations.

The effect of photographic light brightness on cup to disc ratio grading

Background Digital optic disc photographs are integral to remote telehealth ophthalmology, yet no quality control standards exist for the brightness setting of the images. This study evaluated the relationship between brightness setting and cup/disc ratio (c/d) grading among glaucoma specialists. Methods Optic disc photographs obtained during routine examinations under anesthesia were collected to construct an image library. For each optic disc, photographs were obtained at 3 light intensity settings: dark, medium, and bright. From the image library, photograph triads (dark, medium and bright) of 50 eyes (50 patients) were used to construct the study set. Nine glaucoma specialists evaluated the c/d of the study set photographs in randomized order. The relationships between the brightness levels and the c/d grading as well as graders’ years in practice and variability were evaluated. Results The c/d were graded as significantly larger in bright photographs when compared to photographs taken at the medium light intensity (0.53 vs 0.48, P < 0.001) as well as those taken at the dark setting (0.47, P < 0.001). In addition, no relationship was found between ophthalmologists’ years in practice and the variability of their c/d grading (P = 0.76). Conclusion Image brightness affects c/d grading of nonstereoscopic disc photographs. The brighter intensity is associated with larger c/d grading. Photograph brightness may be an important factor to consider when evaluating digital disc photographs.

Comparison of conventional and wide field direct ophthalmoscopy on medical students’ self-confidence for fundus examination: a 1-year follow-up

Background Fundus examination is an easy, quick and effective way to diagnose sight- and life-threatening diseases. However, medical students and physicians report lack of proficiency and self-confidence in perform fundoscopy. The aim of this study was to compare students’ self-confidence in fundus examination, using two different direct ophthalmoscopes, 1 month and 1 year after practical training. Methods In this prospective cohort, medical students (MS) of the same class were divided in small groups for PanOptic (PO) or conventional (CO) direct ophthalmoscope training. The intervention group encompassed MS of the 4th -year (class of 2019), and the control group encompassed MS of year behind (class of 2020). A questionnaire to measure self-confidence in fundoscopy technique assessing optic nerve, cup-to-disc ratio and macula was translated and validated to Portuguese, and applied 1-month and 1-year after practical training. Results One-hundred and sixty-seven MS were enrolled (35 PO group, 38 CO group, and 94 control group). PO group had a significantly higher overall self-confidence comparing either control or CO groups, respectively (3.57 ± 0.65 vs. 2.97 ± 1.03 vs. 2.46 ± 0.87, p < 0.01) as well as in evaluate cup-to-disc ratio (3.09 ± 0.75 vs. 2.32 ± 0.87 vs. 1.46 ± 0.81, p < 0.01), optic disc margins (3.26 ± 0.85 vs. 2.71 ± 0.96 vs. 2.01 ± 0.97, p < 0.01) and macula (3.43 ± 1.12 vs. 2.89 ± 1.08 vs. 2.02 ± 0.89, p < 0.01) 1-month after practical training. One-year after intervention, CO group showed a significantly higher score compared to PO group in overall self-confidence (3.31 ± 0.69 vs. 3.18 ± 0.73, p = 0.03) and in optic disc margins assessing (3.16 ± 0.85 vs. 2.95 ± 0.78, p = 0.03), but not significant in the evaluation of cup-to-disc ratio (2.78 ± 0.97 vs. 2.68 ± 0.94, p = 0.08), and macula (3.34 ± 0.79 vs. 3.27 ± 0.98, p = 0.07). Conclusions Students were more confident in use PO as an instrument to perform direct ophthalmoscopy immediately after practical training, but confidence level of CO was higher compared to PO one year after practical training. These findings would help medical schools decide which ophthalmoscope to choose to teach fundus examination.

Association of the SNP rs112369934 near TRIM66 Gene with POAG Endophenotypes in African Americans

We investigated the association of the single nucleotide polymorphism (SNP) rs112369934 near the TRIM66 gene with qualitative and quantitative phenotypes of primary open-angle glaucoma (POAG) in African Americans (AA). AA subjects over 35 years old were recruited for the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study in Philadelphia, PA. Glaucoma cases were evaluated for phenotypes associated with POAG pathogenesis, and the associations between rs112369934 and phenotypes were investigated by logistic regression analysis and in gender-stratified case cohorts: The SNP rs112369934 was found to have a suggestive association with retinal nerve fiber layer (RNFL) thickness and cup-to-disc ratio (CDR) in 1087 male AA POAG cases, individuals with the TC genotype having thinner RNFL (95% CI 0.85 to 6.61, p = 0.01) and larger CDR (95% CI −0.07 to −0.01, p = 0.02) than those with wildtype TT. No other significant associations were found. In conclusion SNP rs112369934 may play a role in POAG pathogenesis in male AA individuals. However, this SNP has been implicated in higher POAG risk in both male and female AA POAG cases.

LMX1B Locus Associated with Low-Risk Baseline Glaucomatous Features in the POAAGG Study

Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide and has been associated with multiple genetic risk factors. The LMX1B gene is a genetic susceptibility factor for POAG, and several single-nucleotide polymorphisms (SNPs) were shown to be associated with POAG in our own prior Primary Open-Angle African American Glaucoma Genetics (POAAGG) study genome-wide association study (GWAS). This study evaluated the association of the LMX1B locus with baseline optic disc and clinical phenotypic characteristics of glaucoma patients from our African American cohort. Compared to the GG genotype in SNP rs187699205, the GC genotype in this SNP was found to be significantly associated with a smaller cup-to-disc ratio (CDR) and increased (better) visual field mean deviation (MD) in glaucoma cases. None of the glaucoma cases with the GC genotype had disc hemorrhages, disc notching, or beanpot disc appearance. In conclusion, glaucoma phenotypes differed significantly by LMX1B variant in African American patients with POAG, and a SNP variant was associated with certain disease features considered lower risk.