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The usefulness of the Inferior>Superior>Nasal>Temporal (ISNT) rule for the neuroretinal rim (NRR) has been widely used in differentiating normal eyes from glaucoma, but only a few studies have assessed whether this classical ISNT rule applies to the retinal nerve fibre layer (RNFL). This study aimed to determine the applicability of the ISNT rule for the peripapillary RNFL thickness in normal eyes using Spectral Domain Optical Coherence Tomography (SD-OCT) and assess if variants of the ISNT rule apply. A cross-sectional study was conducted on 120 eyes of 62 healthy subjects who fulfilled the study criteria. Peripapillary RNFL thickness was measured by OCT scan and each eye's global, superior, temporal, nasal, and inferior quadrant thickness was noted. The values obtained were analyzed to determine the percentage of eyes obeying the ISNT rule and its variants. The ISNT rule for RNFL thickness was applicable for normal subjects in only 53.33% of cases. Removing the nasal quadrant from analysis increased the number of eyes obeying the IST rule to 71.66%. Further exclusion of the temporal quadrant showed almost the same results (75%) for the IS rule. The ISNT rule for RNFL thickness could be validated in only 53.33% of normal individuals. Though documented as useful for NRR during ophthalmoscopy in glaucoma diagnosis, the ISNT rule did not apply to the quadrant values on RNFL on SD-OCT examination.
PurposeThis systematic review and meta-analysis evaluated the pooled diagnostic accuracy of the ISNT rule non-compliance in detecting glaucoma, considering diverse technique approaches.MethodsA comprehensive literature search was conducted. The primary outcome was the pooled diagnostic accuracy of ISNT rule non-compliance, quantified through various tools. Secondary outcomes included subgroup comparisons based on approach type (neuroretinal rim [NRR] width versus recently described approaches), analysis method (original versus modified), measuring tool, anatomical site evaluated, ISNT rule definition, and the continent where the study was conducted. Risk of bias was assessed using the modified Quality Assessment of Diagnostic Accuracy Studies 2 tool.ResultsA total of twenty-two results derived from six distinct measurement approaches across eighteen studies were included. The pooled diagnostic accuracy estimates were for sensitivity, 0.83 (confidence interval [CI]:0.77-0.88); specificity, 0.49 (CI:0.35-0.63); positive likelihood ratio, 1.60 (CI:1.30-2.15); negative likelihood ratio, 0.37 (CI:0.27-0.49); and diagnostic odds ratio, 4.55 (CI:2.76-7.50). No statistically significant differences were found between subgroup comparisons, except for the specificity of the original method (0.72 [CI:0.67-0.77]), sensitivity of the modified method (0.85 [CI:0.78-0.90]), and sensitivity of the NRR (0.86 [CI:0.79-0.91]).ConclusionsThe ISNT rule presented a low specificity but a high sensitivity for glaucoma diagnosis and may be a useful tool for screening.
To determine what percentage of normal eyes follow the ISNT rule, and whether ISNT rule variants may be more generalizable to the normal population. Cross-sectional study. Setting: Institutional setting. Total of 110 normal subjects. Neuroretinal rim assessments from disc photographs and retinal nerve fiber layer (RNFL) thickness measurements from spectral-domain optical coherence tomography. The percentages of subjects that obeyed the ISNT rule and its variants. The ISNT rule is only valid for 37.0% of disc photograph rim assessments and 43.8% of RNFL measurements. Deviation of the nasal sector from the expected ISNT pattern was a major cause for the ISNT rule not being obeyed for both rim and RNFL assessments. Specifically, 10.9% of subjects had wider nasal rims than the inferior rims, 29.4% had wider nasal rims than the superior rims, 14.7% had narrower nasal rims than the temporal rims, and 42.9% had thinner nasal RNFLs compared to the temporal quadrant. Exclusion of the nasal quadrant from the ISNT rule significantly increased the validity of ISNT variant rules, with 70.9% and 76.4% of disc photographs following the IST rule and the IS rule, respectively. Similarly, for RNFL thickness, 70.9% and 71.8% of patients followed the IST and IS rule, respectively. The ISNT rule is only valid for about a third of disc photographs and less than half of RNFL measurements in normal patients. ISNT rule variants, such as the IST and IS rule, may be considered, as they are valid in more than 70% of patients.
The aim of this study was to compare five different neuroretinal rim (NRR) measurement methods, based on quadrants and NRR widths, in the assessment of the ISNT (inferior (I) > superior (S) > nasal (N) > temporal (T)) rule, and its variants IST (inferior (I) > superior (S) > temporal (S)) rule, IS (inferior (I) > superior (S)) rule and T (temporal is the thinnest) rule in a normal population. Factors influencing compliance with this rule and its variants were also evaluated. Stereoscopic fundus images were analysed through a dichoptic viewing system. Two graders labelled the optic disc and cup, as well as the fovea. Custom-made software automatically determined the limits of the optic disc and cup and examined the ISNT rule and its variants using several NRR measurement methods. Sixty-nine subjects with normal eyes were enrolled. For the various NRR measuring methods, the percentage of eyes following the rules, that is, validity ranges were 0.0%-15.9% for the ISNT rule, 31.9%-59.4% for the IST rule, 46.4%-59.4% for the IS rule and 50.7%-100.0% for the T rule. Significant intra-measurement agreement ranges were IST (κ = 0.50-0.85), IS (κ = 0.68-1.00) and T (κ = 0.24-0.77). Only the IST and IS rules achieved significant inter-measurement agreement (κ = 0.47-1.00). After multivariate and receiver operating characteristic (ROC) curve analyses, the vertical cup position cupy (area under the ROC curve (AUROC) = 0.60-0.96; cut-off = |0.005|) was the most important predictor for virtually all NRR measurement agreements for the ISNT, IST and IS rules. The horizontal cup position (AUROC = 0.50-0.92; cut-off = -0.028 to 0.05) was the most important predictive factor for the majority of the NRR measurement agreements for the T rule. Only the IST and IS rules are valid for the same normal subjects. The most important factor affecting the validity of the ISNT rule and its variants was the anatomical cup position. NRR measurement agreements based on NRR quadrants exhibited larger validity and better agreement. The IST and IS rules can be combined with the alternative SIT (superior (S) > inferior (I) > temporal (T)) and SI (superior (S) > inferior (I)) rules to detect almost all normal subjects.
We determined the applicability of inferior > superior > nasal > temporal (ISNT) rules on retinal nerve fibre layer (RNFL) thickness and rim area and evaluated the impact of various ocular factors on the performance of the ISNT rules in healthy myopic eyes. A total of 138 eyes from 138 healthy myopic subjects were included in this cross-sectional observational study. The peripapillary RNFL and optic disc in each eye were imaged with Cirrus HD optical coherence tomography (OCT) and Heidelberg Retina Tomograph II (HRT2), respectively. The performance of the inferior > superior (IS), inferior > superior > nasal > temporal (IST) and ISNT rules on RNFL thickness and rim area was determined and compared between low-to-moderate myopia and high myopia. The effects of ocular factors [including axial length, disc area, disc tilt, disc torsion, disc-fovea angle (DFA) and retina artery angle] on the performance of ISNT rules were evaluated with logistic regression analysis. The mean axial length and refractive error were 25.57 ± 1.09 mm (range, 22.52-28.77 mm) and -5.12 ± 2.30 D [range, -9.63 to -0.50 dioptres (D)], respectively. Sixty-three per cent of the healthy eyes were compliant with the ISNT rule on rim area, while ISNT rule on RNFL thickness was followed in only 11.6% of the included eyes. For rim area, smaller disc area was significantly associated with increased compliance of the IS rule (odds ratio: 0.46, p = 0.039), IST rule (odds ratio: 0.46, p = 0.037) and ISNT rule (odds ratio: 0.44, p = 0.030). For RNFL thickness, greater DFA was significantly associated with increased compliance of the IS and IST rules (odds ratio: 1.30, p < 0.001; odds ratio: 1.19, p = 0.006, respectively). In healthy myopic subjects, 88.4% and 37% of eyes did not comply with the ISNT rule on RNFL thickness and rim area, respectively. Due to significant low compliance in healthy eyes, the ISNT rule and its variants have limited potential utility in diagnosing glaucoma in myopic subjects.
To determine the factors that influence the satisfaction of the 'ISNT rule' (neural rim width: inferior ≥ superior ≥ nasal ≥ temporal) in normal and glaucomatous eyes. The medical records of patients that visited Boramae Medical Center, Seoul, Korea, were reviewed. Each group of normal and glaucomatous eyes was divided into subgroups based on whether or not they satisfied the ISNT rule. ISNT rule assessment was performed by measuring the rim width with stereoscopic optic disc photographs using ImageJ software. Logistic regression analysis was performed to determine the factors that affect ISNT rule satisfaction. Seventy-seven normal eyes and 97 glaucomatous eyes were included in the study. The ISNT rule was intact in 59 (76.6%) of the normal eyes and was violated in 71 (73.2%) of the glaucomatous eyes. Logistic regression analysis revealed a significant influence of axial length in violation of the ISNT rule in the normal eye group, while the mean deviation value was a significant factor for violation of the ISNT rule in the glaucomatous eye group. The ISNT rule should be cautiously applied when evaluating normal eyes with long axial lengths. In addition, the ISNT rule might not be as effective for detecting early glaucoma.
To determine whether the ISNT rule (Inferior>Superior>Nasal>Temporal) or the "IST" rule (Inferior>Superior>Temporal) can be applied to the peripapillary retinal nerve fiber layer (RNFL) thickness as measured using Heidelberg Retinal Tomography (HRT) and Optical Coherence Tomography (OCT). This was a cross-sectional study of 189 normal and 42 glaucomatous eyes. RNFL thicknesses measured in different quadrants using HRT and OCT were compared to determine the percentage of eyes obeying the ISNT and IST rule. The HRT-measured mean RNFL thickness in normal eyes showed that 25.9% obeyed the ISNT rule and 70.4% conformed to the "IST" rule. The "IST" rule was able to identify normal eyes better (P=0.040), but had a poor sensitivity (45%) and specificity (70%) to diagnose glaucoma. The OCT-measured average RNFL thickness showed that 47.1% of normal eyes obeyed the ISNT rule and 58.7% conformed to the "IST" rule. Exclusion of the nasal sector also increased the number of glaucomatous eyes conforming to the IST rule (31% obeyed the ISNT rule and 50% obeyed the IST rule). Sensitivities and specificities of the ISNT and the IST rules for OCT-quantified RNFL ranged from 42% to 77%. A larger number of normal eyes obeyed the IST rule compared with the ISNT rule for the RNFL thickness measured by HRT and OCT. Exclusion of the nasal sector from the analysis (IST rule) marginally improved the specificity in diagnosing glaucoma at the cost of the sensitivity, making neither of these parameters (ISNT and IST) likely to be useful clinically.
To evaluate the efficacy of the ISNT rule in normal eyes of Koreans. We retrospectively reviewed medical records of 890 subjects with fundus photographs and evaluated the presence of the cup and ISNT rule satisfaction. If the ISNT rule was violated, the quadrants in which the neuroretinal rim was thinnest and thickest, respectively, were evaluated. Among 890 eyes, 84.7% showed the cup. The subjects without the cup were significantly younger and more hyperopic. Among 754 eyes with the cup, 53.5% showed ISNT rule satisfaction. In 351 eyes violating the ISNT rule, the most common quadrant showing the thickest neuroretinal rim was the inferior (65.5%), and the thinnest, the temporal (98.3%). The cup was absent in 15% of the assessed eyes. Only about half of eyes with the cup showed ISNT rule satisfaction. Even in eyes violating ISNT rule, the inferior was the most common quadrant with the thickest neuroretinal rim and the temporal, the thinnest.
To investigate the applicability of ISNT (inferior ≥ superior ≥ nasal ≥ temporal), IST (inferior ≥ superior ≥ temporal), and T min (temporal quadrant with the minimum value) rules to the peripapillary nerve fiber layer (NFL) thickness and radial peripapillary capillary (RPC) vessel density (VD) using Optical Coherence Tomography (OCT) and OCT angiography (OCT-A). This cross-sectional study included 134 eyes of 74 healthy individuals. NFL thickness and RPC VD were measured in all four quadrants using OCT and OCT-A in order to determine the number of eyes that obey the ISNT, IST, and T min rules. Mean age was 48.8 ± 15.5 (range 25-82) years. The ISNT rule was valid in 52 eyes (38.81%) on OCT and only 12 eyes (8.95%) on OCT-A scans. The IST rule was followed by 83 (61.94%) and 37 (27.61%) eyes on OCT and OCT-A scans respectively. The T min rule was valid in 86 eyes (64.18%) in OCT scans and in 26 eyes (19.4%) in OCT-A scans. The topography of the RPC network does not obey the ISNT rule in healthy eyes. The ISNT rule and its variants were found to be more relevant in OCT NFL thickness measurements compared to OCT-A RPC VD measurements.
We evaluated the applicability of the ISNT rule using Bruch's membrane opening minimum rim width (BMO-MRW) in healthy eyes and eyes with normal tension glaucoma (NTG). In total, 124 healthy eyes and 136 NTG eyes were analyzed. Using 2-dimensional disc photographs, neuroretinal rim (NRR) thickness was measured at the superior, inferior, nasal, and temporal sides of the optic disc. Using spectral domain-optical coherence tomography, BMO-MRW was measured at the same regions. We compared the applicability of the ISNT rule in healthy and NTG eyes between these 2 methods. If the NRR was not clearly distinguished on disc photographs, the eye was classified into the "indistinguishable NRR" group and we only tested applicability of the ISNT rule using BMO-MRW. The specificity of "violation of the ISNT rule" for the diagnosis of glaucoma was higher when BMO-MRW was used (66.3%) than using disc photographs (42.2%), whereas the sensitivity did not show a significant difference between the 2 methods (91.7% vs. 86.5%). Compared with eyes with distinguishable NRR (179 eyes), eyes with indistinguishable NRR (81 eyes) had higher axial length, more negative refractive error, and higher tilt ratio (P<0.001). The diagnostic ability of "violation of ISNT rule" using BMO-MRW was not significantly different between eyes with indistinguishable NRR and those with distinguishable NRR (P>0.05). Application of the ISNT rule using BMO-MRW shows superiority in distinguishing between healthy and glaucomatous optic discs compared with disc photographs. The ISNT rule can be applied using BMO-MRW even when NRR is indistinguishable on disc photographs, such as in myopic tilted discs.
To report the applicability of ISNT (inferior>superior>nasal>temporal) and IST (inferior>superior>temporal) rules on the retinal nerve fibre layer (RNFL) using spectral domain optical coherence tomography (SD-OCT) for detecting early glaucoma. A prospective, cross-sectional study which included 80 eyes of 80 normal subjects and 76 eyes of 76 patients with early glaucoma by Hodapp-Anderson-Parrish classification. All subjects were of age more than 18 years, best corrected visual acuity 20/40 or better and a refractive error within ±5 dioptres (D) sphere and ±3 D cylinder. Control subjects had a normal ocular examination, intraocular pressure <22 mm Hg, no past history of high intraocular pressure, no family history of glaucoma, normal optic disc morphology and visual field. All eyes underwent SD-OCT examination for RNFL analysis. The sensitivity, specificity and likelihood ratio for violation of ISNT and IST rules was calculated for early glaucoma diagnosis. The ISNT rule was followed by 44 (55%) normal and 28 (36.84%) early glaucoma eyes. The IST rule was followed by 48 (60%) normal and 40 (52.63%) early glaucoma eyes. The sensitivity/specificity for violation of ISNT and IST rules for early glaucoma diagnosis was 63.2%/55% and 47.4%/60% respectively. The positive/negative likelihood ratio for ISNT and IST rules was 1.4/0.67 and 1.2/0.88, respectively, for diagnosing early glaucoma. Even though useful during ophthalmoscopy, ISNT and IST rules by themselves don't clearly distinguish normal eyes from those with glaucoma when applied to the quadrant values on RNFL on SD-OCT examination.
To evaluate the accuracy of the ISNT rule (I=inferior, S=superior, N=nasal, T=temporal) and its variants with neuroretinal rim width and retinal nerve fibre layer (RNFL) thickness measurements differentiating normal from glaucomatous eyes. The diagnosis accuracy of the ISNT rule and its variants was evaluated in a population-based study. Neuroretinal rim widths were measured on monoscopic optic disc photographs with an image-processing program. RNFL thickness measurements were obtained with spectral-domain optical coherence tomography (SD-OCT). In this study including 940 normal subjects and 93 patients with glaucoma, the sensitivity of the ISNT rule with optic disc photographs was 94.1% (95% CI 90.2 to 98.1), whereas its specificity was 49.2% (46.9 to 51.6). When using the IST rule, the sensitivity decreased to 69.9% (62.1 to 77.6) with a higher specificity, 87.0% (85.3 to 88.6). All the diagnosis indicators were somewhat lower for the different rules using RNFL thickness: the sensitivity of the ISNT rule was 79.4% (72.6 to 86.2) and its specificity was 34.1% (31.9 to 36.4). With the IST rule, the sensitivity decreased to 50.0% (41.6 to 58.4) while the specificity increased to 64.9% (62.7 to 67.2). The ISNT and IST rules applied to neuroretinal rim width measurement by optic disc photographs are useful and simple tools for differentiating normal from glaucomatous eyes. The translation of these rules to RNFL thickness by SD-OCT is of limited value.
To determine the applicability of the ISNT (inferior>superior>nasal>temporal) and IST (inferior>superior>temporal) rules on retinal nerve fiber layer (RNFL) measurement on spectral-domain optical coherence tomography (SD-OCT) in normal children. A prospective, cross-sectional study including consecutive subjects between the ages of 5-18 years who were born at term (≥37 weeks gestational age) and with a normal birth weight (≥2500 g) presenting to the out-patient department for refractive error examination. RNFL measurement was done on Spectralis SD-OCT. Exclusion criteria were best-corrected visual acuity less than 20/20, spherical equivalent (SE) > ± 5 diopter (D), applanation IOP >21 mmHg, cup-to-disc (C/D) ratio of >0.5, C/D ratio asymmetry of >0.2 between eyes and any retinal or optic disc anomaly as determined by mydriatic fundus examination. Subjects with amblyopia, strabismus, or family history of optic nerve or retinal disease were excluded. Poor cooperation for SDOCT imaging and lack of consent were other exclusion criteria. The ISNT rule on the RNFL was followed only by 30 eyes (23.8 %), while the IST rule was followed by 66 eyes (52.4 %) (p < 0.001). The superior RNFL was thicker than the inferior in 57 eyes (45.2 %) while the temporal RNFL was thicker than the nasal in 63 eyes (50 %). The age, gender, spherical equivalent, and disc size did not predict the followability of the ISNT and IST rules (p > 0.05). The ISNT and the IST rules for RNFL are not universally followed by all normal eyes in children. All deviations should therefore not be considered pathological.
To evaluate the ability of the neuroretinal rim (NRR) rules determined using spectral domain optical coherence tomography (SDOCT) in diagnosing glaucoma and to study the effect of optic disc size and disease severity on the diagnostic ability of these rules. In a cross-sectional study, 125 eyes of 96 glaucoma patients and 96 eyes of 72 control subjects underwent optic nerve head (ONH) imaging with SDOCT. Inferior (I), superior (S), nasal (N) and temporal (T) NRR areas were automatically determined by the sdoct software. Diagnostic abilities of ISNT (I > S > N > T), IT (I > T) and ST (S > T) rules in glaucoma were evaluated using sensitivity, specificity and likelihood ratios (LR). Effect of optic disc size and disease severity [based on mean deviation (MD) on visual fields] on the diagnostic ability of the NRR rules was evaluated using regression models. Sensitivities of ISNT, IT and ST rules were 80.8%, 60.0% and 29.6%, respectively, and the specificities were 32.3%, 84.4% and 93.8%, respectively. Positive LRs of ISNT, IT and ST rules were 1.19, 3.84 and 4.74, respectively, and negative LRs were 0.60, 0.47 and 0.75, respectively. Sensitivities of ISNT (coefficient: -1.06, p = 0.02) and IT (-0.71, 0.05) rules decreased with increasing disc size. Positive LR of IT rule increased significantly (-0.01, 0.04) with decreasing MD, and negative LR of IT rule decreased (got better) significantly (0.26, 0.05) with decreasing disc size. Neuroretinal rim rules, as determined by SDOCT, do not allow robust differentiation of glaucomatous from non-glaucomatous discs.
To determine patterns of peripapillary retinal nerve fiber layer (RNFL) damage in early- and late-stage glaucoma based on the Disc Damage Likelihood Scale (DDLS). This cross-sectional, multi-center study involved 267 eyes of 135 patients aged 18 years or older with suspected or diagnosed glaucoma. Exclusion criteria were high refractive errors, media opacities, trauma history, and systemic conditions affecting the optic disc. After a comprehensive ocular examination, the DDLS was used for glaucoma staging. Disease severity was classified into three zones: green, orange, and red. RNFL thickness was measured in four quadrants using optical coherence tomography. Patterns of RNFL damage were analyzed, especially in terms of the ISNT (inferior>superior>nasal>temporal) rule, and compared between the three groups. The male-to-female ratio was 1.59:1 and the mean age was 45.12±15.76 years. There were statistically significant differences among the groups for average, inferior, superior, and temporal RNFL thickness (p<0.00001). However, the difference in nasal RNFL was insignificant. The ISNT rule was the commonest pattern in the study participants (64.4%) and progressive loss of pattern was observed with increased disease severity. This study revealed an association between disease severity and RNFL thinning in the inferior, superior, and temporal quadrants, while nasal RNFL showed no significant association with disease severity. The ISNT rule was more frequently observed in the early stages and diminished with advanced glaucoma. These results highlight RNFL thinning based on the DDLS as an important marker for glaucoma monitoring. Disk Hasarı Olasılığı Ölçeği’ne (DHOÖ) göre erken ve geç evre glokomda peripapiller retina sinir lifi tabakası (RSLT) hasarı paternlerini belirlemek. Bu kesitsel, çok merkezli çalışmaya, glokom şüphesi veya tanısı olan 18 yaş ve üstü 135 hastanın 267 gözü dahil edilmiştir. Dışlama kriterleri ileri refraksiyon kusuru, medya opasitesi, travma öyküsü ve optik diski etkileyen sistemik hastalıklar olarak belirlendi. Kapsamlı bir oküler muayeneden sonra glokom evrelemesi için DHOÖ kullanıldı. Hastalık şiddeti yeşil, turuncu ve kırmızı olmak üzere üç bölgeye ayrıldı. RSLT kalınlığı optik koherens tomografi kullanılarak dört kadranda ölçüldü. RSLT hasarı paternleri, özellikle ISNT kuralına (inferior>superior>nazal>temporal) göre analiz edildi ve üç grup arasında karşılaştırıldı. Erkek/kadın oranı 1,59:1 ve ortalama yaş 45,12±15,76 yıl idi. Gruplar arasında ortalama, inferior, superior ve temporal RSLT kalınlığı açısından istatistiksel olarak anlamlı fark saptandı (p<0,00001). Ancak, nazal RSLT’deki fark anlamlı değildi. ISNT kuralı, çalışmaya dahil edilen katılımcılarda en yaygın (%64,4) izlenen paterndi ve hastalık şiddetinin artmasıyla birlikte progresif patern kaybı gözlendi. Bu çalışmada, inferior, superior ve temporal kadranlarda hastalık şiddeti ile RSLT incelmesi arasında bir ilişki olduğu bulunurken, nazal RSLT hastalık şiddeti ile anlamlı bir ilişki göstermemiştir. ISNT kuralı erken evrelerde daha sık gözlendi ve ileri glokomda azaldı. Bu sonuçlar, glokom takibinde DHOÖ’ye göre RSLT incelmesinin önemli bir belirteç olduğuna işaret etmektedir.
Evaluate disc-fovea angle (DFA) effect on glaucoma detection in fundus images. Cross-sectional observational study with 907 fundus images. The ONH (optic nerve head) metrics, vertical cup-to-disc ratio (vCDR), and the ISNT rule (inferior > superior > nasal > temporal rim width) and its variants were considered. A custom-made software determined ONH metrics in corrected and uncorrected DFA evaluation scenarios. ONH metrics were calculated with a DFA amplitude of [-30◦; + 20◦] in corrected DFA. The original DFA is used for the uncorrected DFA. Mean uncorrected DFA was -7.59◦ ± 3.61◦, [-19.90◦;-0.07◦]. For a DFA amplitude [-12◦;0◦], there is no significant difference (all p-value > 0.05) between ONH metrics with and without DFA correction. The sensitivity ranges for corrected and uncorrected DFA were, ISNT([0.87;0.95], 0.87), IST([0.56;0.71], 0.58), IS([0.35;0.58], 0.45), and T([0.30;0.42], 0.30). The specificity were, ISNT([0.06;0.24], 0.25), IST([0.35;0.49], 0.48), IS([0.45;0.68], 0.57), and T([0.59;0.72], 0.70). The accuracy achieved more consistent values between [0.25;0.62] for both corrected and uncorrected DFA. The F1-score for the ISNT rule and its variants ranged from [0.25;0.37]. The area under the receiver operating characteristic curve (AUC) ranged from [0.50;0.51], with no significant differences between the corrected and uncorrected DFA evaluation scenarios (all p-value = 1.00). For the corrected DFA scenario, vCDR resulted in the ranges, sensitivity [0.27;0.79], specificity [0.39;0.95], and accuracy [0.47;0.87]. For uncorrected DFA, vCDR resulted in the ranges sensitivity [0.30;0.87], specificity [0.25;0.70], and accuracy [0.38;0.62]. F1-score consistently ranged [0.24;0.38] for both the corrected and uncorrected DFA evaluation scenarios. AUC ranged from 0.71 to 0.72, with no significant differences between the corrected and uncorrected DFA scenarios (all p-value = 1.00). Fundus with DFA ranges of [-12◦;0◦] does not require DFA correction in ONH evaluations. Glaucoma detection in fundus images is not affected by DFA. The influence of DFA on clinical follow-up is uncertain and requires additional research.
Porous organic imine supramolecular nanotubes (ISNTs), as a subclass of synthetic organic molecular nanotubes with nanotubular structures, permanent and confined cavities, and defined transport channels, have recently attracted considerable interest in diverse applications. In this study, a homochiral porous organic ISNT, TCC1-R, was synthesized by condensing 5,5'-(ethyne-1,2-diyl)diisophthalaldehyde with (1R, 2R)-1,2-diaminocyclohexane and used as a stationary phase for gas chromatographic (GC) separations. The statically coated TCC1-R capillary column exhibited outstanding separation performance not only for diverse organic isomers but also for a broad range of racemic compounds. High-resolution separation of 20 organic isomers was achieved on the column, including positional isomers of disubstituted benzenes, structural isomers, and cis-/trans-isomers. The separation of these achiral isomers on the TCC1-R column was compared with that on a commercial HP-35 column and showed some advantages. Of greater importance, 74 racemates were effectively enantioseparated on the column, including the challenging chiral hydrocarbons, nitriles, sulfoxides, ketones, amides, lactones, halohydrocarbons, epoxides, alcohols, amines, aldehydes, esters, and ethers. Moreover, the resolution of all possible enantiomers of some challenging chiral compounds with two chiral centers can also be achieved on this column. Compared with the widely used commercial β-DEX 120 column and our previously proposed porous organic cage-based CC3-R column, the TCC1-R column exhibited superior enantioselectivity for separating these studied racemates. In addition, the column also showed good stability and reproducibility on separation. This study demonstrates that chiral porous organic ISNTs are a highly promising class of stationary phases with promising application prospects in chromatographic separations.
Optic nerve head (ONH) evaluation plays a key role in differentiating normal from glaucomatous disk. Thinning of the inferior neuroretinal rim (NRR) has been noted in early glaucoma. However, NRR thickness in different quadrants appears to depend on various factors including central retinal vessel trunk exit (CRVT) position. We evaluated ocular parameters that determined the NRR thickness in the different quadrants of normal eyes. Retrospective review of demographic and ocular data from 773 eyes of 388 subjects with normal ONH over one year was undertaken. Nearly 54% were males, and the mean age was 43.2 years. The CRVT exit was central in 50% (773). The common site for noncentral CRVT was superotemporal (ST) [37%, 141/384] followed by inferotemporal (IT) [35%, 135/384]. With noncentral CRVT, the probability that the inferior, superior, nasal and temporal (ISNT) rule was not followed was 1.42 times ( P < 0.001). The thinnest rim quadrant (TRQ) was mostly ST (69%) irrespective of CRVT location. The TRQ was IT in 40% when CRVT was noncentral and 82% with IT CRVT exit. With noncentral CRVT, round disks favored noncompliance [132 (54.1%), odds ratio (OR) 2.56] with the ISNT rule. The OR of noncompliance with the ISNT rule increases 1.89 times with inferonasal CRVT and 1.22 times with a unit increase in the axial length. TRQ was IT in IT CRVT, and noncompliance with the ISNT rule was observed with large disks, longer axial length, and noncentral CRVT. This implies that despite the ISNT rule being violated these eyes do not have optic nerve pathology and should not be subjected to unnecessary diagnostic tests.
Introduction Assessment format may influence the extent to which student learning approaches are reflected in performance, yet whether constructed-response descriptive assessments (DAs) and selected-response multiple-choice question assessments (MCQAs) differ in their sensitivity to variation in learning approach within formative physiology education has not been directly examined. This study tested whether baseline deep and surface learning approaches were differentially associated with performance in DAs and MCQAs within a longitudinal formative undergraduate medical physiology programme. Methods This three-month longitudinal observational study was conducted at a single medical college in South India. Among 150 invited first-year medical students, 109 completed the baseline Revised Two-Factor Study Process Questionnaire (R-SPQ-2F) and contributed to the study. Eight physiology topics, selected through a modified Delphi process, were taught sequentially and assessed on a rolling basis. For each topic, students completed both a DA and an MCQA in the same sitting, with items matched on construct and revised Bloom's taxonomy level. A linear mixed-effects model was used to test whether the association between learning approach and marks differed by assessment format, with a student-level random intercept to account for repeated observations. A post hoc inter-rater reliability audit was conducted on a randomly selected subset of DA scripts. Sensitivity analyses included a random-slopes model and a Deep-minus-Surface composite parameterisation. Results The association between learning approach and marks differed by assessment format, with significant format-by-deep-learning and format-by-surface-learning interactions (both p < 0.001). Within DAs, higher deep-learning scores were associated with higher marks (β = 0.032, p = 0.022), whereas higher surface-learning scores were associated with lower marks (β = -0.038, p = 0.003). Within MCQAs, neither learning-approach dimension was significantly associated with marks. The negative association between surface learning and DA performance remained robust across model specifications, whereas the positive association between deep learning and DA performance was attenuated in the random-slopes model (p = 0.072). The Deep-minus-Surface sensitivity analysis supported the same overall format-dependent pattern. A post hoc inter-rater reliability audit on 25% of DA scripts yielded strong agreement with an intraclass correlation coefficient (ICC) of 0.87. Conclusions Assessment format moderated the association between learning approach and assessment performance in this cohort: DAs showed clearer differentiation by learning approach than MCQAs, with poorer DA performance at higher surface-learning scores. These findings do not show that MCQAs reward surface learning but suggest that DAs may provide more discriminating information about variation in learning approach than MCQAs within a programmatic assessment framework.
Glaucoma is a leading cause of blindness, requiring early detection for effective management. Traditional diagnostic methods have challenges such as precise segmentation of small structures and accurate classification of disease stages remain. This research addresses these challenges by developing an optimized hybrid classification model for automated glaucoma diagnosis. At first, the preprocessing stage employs the histogram equalization technique known as Contrast Limited Adaptive Histogram Equalization (CLAHE) technique. Consequently, an improved U-Net segmentation process implemented with the proposed cross-entropy loss function is utilized. Then, features such as fractal features, cup-to-disc-based features, Inferior-Superior-Nasal-Temporal (ISNT) rule-based features and improved Pyramid Histogram of Orient Gradient (PHOG) based features are extracted. Further, a hybrid classification model, a combination of Improved Convolutional Neural Network (ICNN) and optimized Recurrent Neural Network (RNN) classifiers for diagnosing glaucoma disease. Also, to improve the performance of the diagnosis process, a new Opposition-based Learning-enabled Namib Beetle Optimization (OBL-NBO) approach is proposed to optimize the weights of the RNN classifier. Moreover, the ICNN classifier is employed for classifying the presence of glaucoma and non-glaucoma conditions. The proposed OBL-NBO scheme achieved an accuracy of 0.927 for dataset 1 and 0.945 for dataset 2 at an 80% training data.