Systematic bias in real-world tonometry readings based on laterality?

AIMS: In research settings, the first eye examined tends to have a higher intraocular pressure (IOP) than the second. We sought to verify whether clinicians in Yorkshire, UK, measure IOP in right eyes before left and whether such behavioural factors affect IOP readings at the population level. METHODS: We observed 128 IOP measurements taken by 28 ophthalmologists using Goldmann applanation tonometry (GAT) over a 4-month period in 2018, recording which eye was examined first. All IOP measurements on electronic patient records for Leeds Teaching Hospitals NHS Trust, UK, between January 2002 and June 2017 were extracted, yielding IOP readings for 562,360 eyes, analysed for evidence of systematic bias in IOP measurement. RESULTS: Right eye IOP was measured before left in 112/128 observations (87.5% (95% CI: 75.2%-94.2%)). For IOP measured by GAT, there was no statistically significant difference (p = 0.121) between right and left eye IOP (mean IOP 16.95 and 16.96 mmHg, respectively). Even values of IOP were reported more frequently than odd values (136,503/214,628 (63.6%) were even). Identical IOP readings for both eyes were recorded in 124,392/254,380 patients (48.9%) who had both eyes measured. CONCLUSIONS: Our study found no IOP difference based on laterality, but strong evidence of certain trends associated with IOP measurement by GAT, such as a preference for even values and the same IOP being recorded for both left and right eyes. Such effects may be explained by behavioural aspects of GAT and suggest that there are substantial opportunities for improvement in the way GAT is utilised in real world settings

Compositional analysis of extracellular aggregates in the eyes of patients with exfoliation syndrome and exfoliation glaucoma

Purpose: Exfoliation syndrome (XFS) is a condition characterized by the production of insoluble fibrillar aggregates (exfoliation material; XFM) in the eye and elsewhere. Many patients with XFS progress to exfoliation glaucoma (XFG), a significant cause of global blindness. We used quantitative mass spectrometry to analyze the composition of XFM in lens capsule specimens and in aqueous humor (AH) samples from patients with XFS, patients with XFG and unaffected individuals. Methods: Pieces of lens capsule and samples of AH were obtained with consent from patients undergoing cataract surgery. Tryptic digests of capsule or AH were analyzed by high-performance liquid chromatography-mass spectrometry and relative differences between samples were quantified using the tandem mass tag technique. The distribution of XFM on the capsular surface was visualized by SEM and super-resolution light microscopy. Results: A small set of proteins was consistently upregulated in capsule samples from patients with XFS and patients with XFG, including microfibril components fibrillin-1, latent transforming growth factor-β-binding protein-2 and latent transforming growth factor-β-binding protein-3. Lysyl oxidase-like 1, a cross-linking enzyme associated with XFS in genetic studies, was an abundant XFM constituent. Ligands of the transforming growth factor-β superfamily were prominent, including LEFTY2, a protein best known for its role in establishing the embryonic body axis. Elevated levels of LEFTY2 were also detected in AH from patients with XFG, a finding confirmed subsequently by ELISA. Conclusions: This analysis verified the presence of suspected XFM proteins and identified novel components. Quantitative comparisons between patient samples revealed a consistent XFM proteome characterized by strong expression of fibrillin-1, lysyl oxidase-like-1, and LEFTY2. Elevated levels of LEFTY2 in the AH of patients with XFG may serve as a biomarker for the disease

Effect of cataract and its removal on signal strength and peripapillary retinal nerve fiber layer optical coherence tomography measurements

To assess the effect of cataract on optical coherence tomography (OCT), signal strength (SS), and peripapillary retinal nerve fiber layer (RNFL) thickness measurements. Peripapillary RNFL thickness measurements were obtained by Stratus OCT scans using the Fast RNFL thickness (3.4) acquisition protocol before and after cataract extraction in 45 patients with cataract, including 23 glaucoma patients. Cataracts were graded according to the Lens Opacities Classification System III. The postoperative RNFL thickness and SS were 9.3% (P=0.001) and 24.1% (P<0.001) higher than before surgery, respectively. There was greater postoperative change in RNFL thickness measurements in patients with lower preoperative RNFL measurements (r=-0.63, P<0.001) and SS (r=-0.59, P<0.001). Eyes with preoperative SS more than 6 had no significant difference between precataract and postcataract surgery RNFL thickness (P=0.14). There was no significant difference in RNFL thickness change between eyes with cataract only (10.9±20.8 μm) and those with cataract and glaucoma (7.0±14.7 μm; P=0.81). Cataracts may decrease peripapillary RNFL thickness measurements and the SS on OCT scans. Thinning of the peripapillary RNFL suggestive of glaucomatous progression may be the result of artifact from advancing cataract rather than actual structural changes in the peripapillary RNFL. Peripapillary RNFL thickness measurements should be interpreted with caution in glaucomatous eyes with significant cataract, particularly if the SS is attenuated

The Utility of the Monocular Trial: Data from the Ocular Hypertension Treatment Study

OBJECTIVE: To determine whether adjusting the intraocular pressure (IOP) change of the trial eye for the IOP change of the fellow eye (i.e., the monocular trial) is a better assessment of medication response than testing each eye independently. DESIGN: Analysis of data from a prospective, randomized clinical trial. PARTICIPANTS: Two hundred and six participants with ocular hypertension randomized to the observation group and later started on a topical prostaglandin analogue (PGA). METHODS: Participants were instructed to instill a topical PGA in one eye once daily and returned in 4–6 weeks to determine medication response. IOP response of the trial eye was determined by the IOP change between baseline and 1 month in the trial eye alone (unadjusted method) and by adjusting for the IOP change in the fellow eye between the same visits (adjusted method). We defined our “gold standard” for medication response as the IOP change in the trial eye using up to 3 pre- and 3 post-treatment visits on the same medication. Pearson correlation was used to compare the unadjusted and adjusted methods to the gold standard. In addition, symmetry of IOP response between trial and fellow eyes to the same medication was determined by correlating the IOP change of the trial eye using up to 3 pre-and 3 post-treatment visits to the IOP change of the fellow eye between the same visits. MAIN OUTCOME MEASURES: Correlations of IOP change of the trial eye using the gold standard to the IOP change of the trial eye using the unadjusted and adjusted methods. RESULTS: The correlations of IOP change using the gold standard to the IOP change using the unadjusted and adjusted methods were r=0.40 and r=0.41, respectively. The correlation of IOP change of both eyes between the same pre-and post-treatment visits was r=0.81. CONCLUSIONS: The monocular trial (i.e., adjusted method) appears equivalent to testing each eye independently (i.e., unadjusted method) however neither method is adequate to determine medication response to topical PGAs. Both eyes have a similar IOP response to the same PGA. Further studies to understand IOP fluctuation are necessary to improve current methods of assessing medication response

Asymmetries and visual field summaries as predictors of glaucoma in the ocular hypertension treatment study

PURPOSE. To evaluate whether baseline visual field data and asymmetries between eyes predict the onset of primary open-angle glaucoma (POAG) in Ocular Hypertension Treatment Study (OHTS) participants. METHODS. A new index, mean prognosis (MP), was designed for optimal combination of visual field thresholds, to discriminate between eyes that developed POAG from eyes that did not. Baseline intraocular pressure (IOP) in fellow eyes was used to construct measures of IOP asymmetry. Age-adjusted baseline thresholds were used to develop indicators of visual field asymmetry and summary measures of visual field defects. Marginal multivariate failure time models were constructed that relate the new index MP, IOP asymmetry, and visual field asymmetry to POAG onset for OHTS participants. RESULTS. The marginal multivariate failure time analysis showed that the MP index is significantly related to POAG onset (P &lt; 0.0001) and appears to be a more highly significant predictor of POAG onset than either mean deviation (MD; P = 0.17) or pattern standard deviation (PSD; P = 0.046). A 1-mm Hg increase in IOP asymmetry between fellow eyes is associated with a 17% increase in risk for development of POAG. When threshold asymmetry between eyes existed, the eye with lower thresholds was at a 37% greater risk of development of POAG, and this feature was more predictive of POAG onset than the visual field index MD, though not as strong a predictor as PSD. CONCLUSIONS. The MP index, IOP asymmetry, and binocular test point asymmetry can assist in clinical evaluation of eyes at risk of development of POAG.</p