Comparison of intraocular pressure profiles during the water drinking test and the modified diurnal tension curve.

OBJECTIVES: To compare intraocular pressure (IOP) during the water drinking test (WDT) and modified diurnal tension curve (mDTC) in open-angle glaucoma (OAG) patients, using multimodal, observer-masked tonometry. METHODS: Open-angle glaucoma subjects were prospectively enroled, excluding those who had undergone glaucoma filtration or laser surgery. Two-hourly mDTC Goldmann applanation (GAT) and rebound tonometry (RT) was performed between 8:00 and 16:00, and every 15 min for 45 min after ingestion of 800mls of water. Blood pressure, heart rate, pupillometry measurements, and optical coherence tomography (AS-OCT) were also recorded. RESULTS: Forty-two subjects' right eyes were included. 48% were using topical glaucoma medication. Mean baseline IOP was 14.9 ± 4.52 mmHg, with mean visual field mean deviation (±SD) -5.05 ± 5.45 dB. Strong association was found between maximum IOP during mDTC and WDT (r = 0.90, 95% CI 0.82-0.95 p < 0.0001) with agreement (mDTC-WDT) bias -0.82 mmHg, 95% LoA -1.46 to -0.18. During the WDT, mean systolic blood pressure (±SD) increased from 140.0 ± 20.0 to 153.3 ± 24.0 mmHg (p < 0.0001), mean heart rate ( ± SD) reduced from 69.5 ± 11.3 bpm to 63.6 ± 10.0 bpm (p < 0.0001), and temporal iridocorneal angle increased from 29.2 ± 6.0° to 29.6 ± 5.2° (p = 0.04). CONCLUSION: This study presents repeated, observer-masked IOP data showing strong correlation between maximum IOP during mDTC and WDT using multimodal tonometry. This supports WDT as a meaningful alternative to mDTC when investigating diurnal IOP characteristics in clinic, with reduced time requirements and associated costs.

Effects of COVID-19 pandemic on glaucoma appointment scheduling in a tertiary hospital in London, UK.

PURPOSE: To investigate the impact of the delay in patient appointments caused by the COVID-19 pandemic and the triage system on the glaucomatous disease of patients in a London tertiary hospital. METHODS: Observational retrospective study that randomly selected 200 glaucoma patients with more than 3 months of unintended delay for their post-COVID visit and other inclusion and exclusion criteria. Demographic information, clinical data, number of drugs, best-corrected visual acuity (BCVA), intraocular pressure (IOP), visual field (VF) mean deviation (MD), and global peripapillary retinal nerve fibre layer (pRNFL) thickness were obtained from the pre- and post-COVID visit. At the post-COVID visit, the clinical outcomes subjective clinical concern and change of treatment or need for surgery were also annotated. The variables were stratified by glaucoma severity (according to the MD into early, moderate and advanced) and by delay time (more and less than 12 months) and analysed using SPSS. RESULTS: We included 121 eyes (from 71 patients). The median patient age was 74 years (interquartile range -IQR- 15), 54% were males and 52% Caucasians. Different glaucoma types and all glaucoma severities were included. When data was stratified for glaucoma severity, at the pre-COVID visit, significant differences in BCVA, CCT and IOP were observed and there were significantly higher values in the early glaucoma group. The median follow-up delay was 11 months (IQR 8), did not differ between the glaucoma severity groups and did not correlate to the glaucoma severity. At the post-COVID visit, significant differences in BCVA, IOP, and Global pRNFL thickness were observed between the glaucoma severity groups, as lower BCVA and higher IOP and pRNFL thickness were observed in the early glaucoma group. At the post-COVID visit there was cause for concern in 40 eyes: 5 were followed more closely, 22 had a change of treatment and 13 were booked for surgery (3 for cataract and 10 for glaucoma surgery). However, the number of eyes with causes for concern were similar between the glaucoma severity groups and there was no correlation between these clinical outcomes and the delay of the post-COVID visit. The number of topical hypotensive medications increased significantly after the post-COVID visit, higher number of medications were observed in the advanced glaucoma group. When differences of IOP, MD and pRNFL thickness between the pre and post-COVID visit, only the MD difference was significantly different between the glaucoma severity groups because it was higher in the severe group. When data was stratified for delay longer or shorter than 12 months, no differences were observed between the groups except at the pre-COVID visit, when the numbers of patients with MD deviation >-6 dB had longer delay time. When differences in IOP, MD and RNFL thickness were calculated, only the pRNFL thickness showed significant differences between the delay groups, because it was higher in the longer delay group. Finally, when paired analysis of the variables at the pre- and post-COVID visits, stratified by glaucoma severity and delay were conducted, although there were no significant differences in IOP in any group, the BCVA decreased significantly in the overall group and in the longer delay groups, the number of hypotensive drugs increased significantly overall and in the moderate and advanced glaucoma, the MD of the VF worsened significantly in the overall group and in the early glaucoma and longer delay groups and the pRNFL thickness decreased significantly in all groups. CONCLUSIONS: We document that delayed care impacts negatively on the glaucomatous disease of our patients because at the post-COVID visit there were reasons for clinical concern in a third of eyes that resulted in change of treatment or surgery. However, these clinical consequences were not related to IOP, glaucoma severity or delay time and reflect that the triage methods implemented worked adequately. The most sensitive parameter to indicate progression in our sample was the pRNFL thickness.

Factors impacting participation in research during the COVID-19 pandemic: results from a survey of patients in the ophthalmology outpatient department.

BACKGROUND: Understanding public and patient attitudes to clinical research is paramount to successful recruitment. The COVID-19 pandemic has led to additional hurdles in achieving this. Our aim is to understand the current factors and attitudes towards clinical trial participation in order to assist in recruitment to clinical trials. METHODS: We conducted face-to-face interviews with patients in the outpatient department at a tertiary eye hospital facilitated by a 32-item questionnaire developed by the research team. Patient characteristics were correlated with their responses, in addition to qualitative thematic text analysis. RESULTS: A total of 53 patients were interviewed. Forty per cent indicated that they would be willing to participate in clinical research in the current climate. General motivating factors for involvement in research included personal gain, altruism and contribution to innovation. Factors limiting participation included concerns regarding own safety, inconvenience, accessibility and lack of benefit. 22.6% of participants felt that the COVID-19 pandemic has changed their outlook on research. These were categorised into positive (increased awareness of the importance and need for research, altruism) and negative (increased anxiety, need to minimise exposure to the hospital environment) influences. CONCLUSIONS: Factors influencing patients' decisions to participate in trials are similar to those observed prior to COVID-19 but with an increased focus on the environment the research is conducted in. The COVID-19 pandemic has had positive and negative impacts on patient attitudes towards research. Trial design, with a particular focus on setting and safety measures, in reassuring patients is increasingly important.

Glaucoma Rose Plot Analysis: Detecting Early Structural Progression Using Angular Histograms.

PURPOSE: To evaluate the novel Rose Plot Analysis (RPA) in the analysis and presentation of glaucoma structural progression data. DESIGN: Case-control image analysis study using retrospective retinal imaging series. SUBJECTS: Subjects with open-angle glaucoma with at least 5 registered spectral-domain OCT scans. METHODS: Glaucoma RPA was developed, combining a novel application of angular histograms and dynamic cluster analysis of circumpapillary retinal nerve fiber layer (cRNFL) OCT data. Rose Plot Analysis plots were created for each eye and each visit. Significant clusters of progression were indicated in red. Three masked clinicians categorized all RPA plots (progressing, not progressing), in addition to measuring the significant RPA area. A masked OCT series assessment with linear regression of averaged global and sectoral cRNFL thicknesses was conducted as the clinical imaging standard. MAIN OUTCOME MEASURES: Interobserver agreement was compared between RPA and the clinical imaging standard. Discriminative ability was assessed using receiver-operating characteristic curves. The time to detection of progression was compared using a Kaplan-Meier survival analysis, and the agreement of RPA with the clinical imaging standard was calculated. RESULTS: Seven hundred fourty-three scans from 98 eyes were included. Interobserver agreement was significantly greater when categorizing RPA (κ, 0.86; 95% confidence interval [CI], 0.81-0.91) compared with OCT image series (κ, 0.66; 95% CI, 0.54-0.77). The discriminative power of RPA to differentiate between eyes that were progressing and not progressing (area under the curve [AUC], 0.97; 95% CI, 0.92-1.00) was greater than that of global cRNFL thickness (AUC, 0.71; 95% CI, 0.59-0.82; P < 0.0001) and equivalent to that of sectoral cRNFL regression (AUC, 0.97; 95% CI, 0.92-1.00). A Kaplan-Meier survival analysis showed that progression was detected 8.7 months sooner by RPA than by global cRNFL linear regression (P < 0.0001) in progressing eyes but was not sooner than with sectoral cRNFL (P = 0.06). Rose Plot Analysis showed substantial agreement with the presence of significant thinning on sectoral cRNFL linear regression (κ, 0.715; 95% CI, 0.578-0.853). CONCLUSIONS: Rose Plot Analysis has been shown to provide accurate and intuitive, at-a-glance data analysis and presentation that improve interobserver agreement and may aid early diagnosis of glaucomatous disease progression.

Endocyclophotocoagulation combined with phacoemulsification in surgically naive primary open-angle glaucoma: three-year results.

OBJECTIVE: To assess the safety and efficacy of endocyclophotocoagulation with phacoemulsification (phaco-ECP) in surgically naive, primary open-angle glaucoma (POAG). METHODS: A retrospective case series of patients undergoing phaco-ECP between 2007 and 2017 at a single centre in London, UK. The primary outcome was intraocular pressure (IOP). Secondary outcomes were visual acuity, visual field global indices, topical medications and surgical complications. Failure criteria were: (1) IOP > 21 mmHg or <20% reduction at two consecutive visits, (2) IOP <5 mmHg and (3) further IOP-lowering surgery. RESULTS: Eighty-three eyes from 83 patients were eligible. Pre-operatively, mean IOP (±SD) was 18.4 ± 5.2 mmHg. The mean number of topical agents (±SD) was 2.7 ± 0.9. Mean IOP (±SD) significantly reduced to 14.3 ± 4.7 at 1 year, 14.1 ± 4.0 at 2 years and 13.6 ± 3.7 at 3 years (p < 0.0001). Topical medications were significantly reduced to 1.3 ± 1.2 at 1 year, 1.7 ± 1.2 at 2 years and 1.8 ± 1.3 at 3 years (p < 0.0001). Annual IOP 'survival' was 70%, 54% and 45% at year 1, 2 and 3, respectively. Complications included uveitis (6%), macular oedema (2%), IOP spikes (1%) and corneal decompensation (1%) with no episodes of hypotony or retinal detachment. One patient underwent filtration surgery within 3 years (1%). CONCLUSION: Phaco-ECP facilitates significant IOP lowering and reduction of medication burden in surgically naive POAG requiring cataract extraction. The procedure is relatively safe and without the use of implants and their associated risks.

Recent Advancements in the Medical Treatment of Diabetic Retinal Disease.

Diabetic retinal disease remains one of the most common complications of diabetes mellitus (DM) and a leading cause of preventable blindness. The mainstay of management involves glycemic control, intravitreal, and laser therapy. However, intravitreal therapy commonly requires frequent hospital visits and some patients fail to achieve a significant improvement in vision. Novel and long-acting therapies targeting a range of pathways are warranted, while evidence to support optimal combinations of treatments is currently insufficient. Improved understanding of the molecular pathways involved in pathogenesis is driving the development of therapeutic agents not only targeting visible microvascular disease and metabolic derangements, but also inflammation and accelerated retinal neurodegeneration. This review summarizes the current and emerging treatments of diabetic retinal diseases and provides an insight into the future of managing this important condition.

A Functional Radiological and Soft Tissue Classification to Predict Outcomes in Orbital Fracture Surgery in a Multidisciplinary "Real-World" Setting.

Purpose: The decision for open reduction and internal fixation (ORIF) of orbital fractures is usually based on clinical severity and soft tissue and bony findings. This study aimed to identify prognostic factors for a successful surgical outcome. Materials and Methods: We included all orbital fractures treated by ORIF referred to the Ophthalmology clinic for assessment over a 12-year period. A successful outcome was defined as (i) a single operation, (ii) improved diplopia and globe position at 6 months, (iii) no surgical complications, and (iv) patient satisfaction. Data was collected on presenting symptoms, orthoptic measurements, time interval from injury to surgery, fracture geometry and involvement of internal, and external bony landmarks. Univariate and multivariate regression was used to identify predictive factors for success. Results: There were 143 cases with median age 35.4 years and 81.8% (117/143) male. 51% (73/143) were complex fractures involving multiple orbital walls. 63.6% (91/143) achieved significant improvement in both enophthalmos and diplopia at 6 months. 15.3% (22/143) had significant preoperative soft tissue or neurogenic injury. 11.8% (17/143) required orbital plate repositioning or removal. 1.4% (2/143) developed orbital haematoma and 4.2% (6/143) had cicatricial entropion. Pre-operative nerve or muscle damage (OR 0.05, p = 0.01) and infraorbital fissure fracture (OR 0.38, p = 0.04) were associated with poor outcomes, whereas an intact posterior ledge was associated with successful outcomes (OR 3.03, p = 0.02). Conclusion: Careful ocular motility evaluation to ascertain neurogenic injury and muscle compartment syndrome, and radiological analysis of the integrity of the posterior ledge and the inferior orbital fissure can facilitate management and expectations of ORIF surgery.

Apoptosis in health and diseases of the eye and brain.

Apoptosis is a form of programmed cell death (PCD) and enables the immunologically silent disposal of senescent or unwanted cells, causing minimal damage to the surrounding environment. Apoptosis can occur via intrinsic or extrinsic pathways that initiate a series of intracellular and extracellular signaling events. This ultimately leads to the clearance of the cell by phagocytes. This normal physiological mechanism may be accelerated in several diseases including those involving the eyes and brain, leading to loss of structure and function. This review presents the role of PCD in the health of the eyes and brain, and the evidence presented for its aberrant role in disease.

The efficacy of dexamethasone implants following anti-VEGF failure for macular oedema in retinal vein occlusion.

PURPOSE: To investigate the efficacy of intravitreal dexamethasone implants (DEX) after anti-VEGF failure in retinal vein occlusion macular oedema. METHODS: Retrospective cohort study of DEX implant (0.7 mg) given after anti-VEGF 'failure'. Switch to DEX occurred if a ⩽ +5 ETDRS letter gain and ⩽20% reduction in central subfield thickness was present following ⩾6 consecutive anti-VEGF injections. The primary endpoint was VA change 30 days after DEX. Secondary outcomes were peak VA change, VA change at monthly timepoints, percentage achieving 15-letter gain, central subfield thickness (CST) and intraocular pressure (IOP). RESULTS: Sixty-two injections in 62 patients associated with 26% central retinal vein occlusion (CRVO) and 74% branch retinal vein occlusion (BRVO) were eligible. There was a modest, significant improvement in mean VA change at 30 days compared to baseline (+6 letters, 95% CI +2.2 to +9.1 letters, p < 0.01). DEX implant significantly improved mean peak VA change compared to preceding anti-VEGF by +18.1 letters in CRVO (p = 0.002) and +13.2 letters in BRVO (p < 0.0001). IOP peaked between 30 and 60 days following injection, with 31% of CRVO and 11% of BRVO patients experiencing an IOP ⩾ 25 mmHg. CONCLUSION: DEX implant provides useful rescue therapy in cases of anti-VEGF 'failure' for macular oedema following retinal vein occlusion, resulting in improved functional outcomes at 30 days.

Detecting Apoptosis as a Clinical Endpoint for Proof of a Clinical Principle.

The transparent eye media represent a window through which to observe changes occurring in the retina during pathological processes. In contrast to visualising the extent of neurodegenerative damage that has already occurred, imaging an active process such as apoptosis has the potential to report on disease progression and therefore the threat of irreversible functional loss in various eye and brain diseases. Early diagnosis in these conditions is an important unmet clinical need to avoid or delay irreversible sight loss. In this setting, apoptosis detection is a promising strategy with which to diagnose, provide prognosis and monitor therapeutic response. Additionally, monitoring apoptosis in vitro and in vivo has been shown to be valuable for drug development in order to assess the efficacy of novel therapeutic strategies both in the pre-clinical and clinical setting. Detection of Apoptosing Retinal Cells (DARC) technology is to date the only tool of its kind to have been tested in clinical trials, with other new imaging techniques under investigation in the fields of neuroscience, ophthalmology and drug development. We summarise the transitioning of techniques detecting apoptosis from bench to bedside, along with the future possibilities they encase.

Cellular Consequences of Coenzyme Q10 Deficiency in Neurodegeneration of the Retina and Brain.

Coenzyme Q10 (CoQ10) is a ubiquitous cofactor in the body, operating in the inner mitochondrial membrane, where it plays a vital role in the generation of adenosine triphosphate (ATP) through the electron transport chain (ETC). In addition to this, CoQ10 serves as an antioxidant, protecting the cell from oxidative stress by reactive oxygen species (ROS) as well as maintaining a proton (H+) gradient across lysosome membranes to facilitate the breakdown of cellular waste products. Through the process of ageing, the body becomes deficient in CoQ10, resulting in several systemic manifestations. On a cellular level, one of the consequences of CoQ10 deficiency is apoptosis, which can be visualised in tissues of the central nervous system (CNS). Diseases affecting the retina and brain such as age-related macular degeneration (AMD), glaucoma, Alzheimer's disease (AD) and Parkinson's disease (PD) have shown defects in cellular biochemical reactions attributed to reduced levels of CoQ10. Through further research into the pathogenesis of such conditions, the effects of CoQ10 deficiency can be counteracted through supplementation, early detection and intervention.

Retinal correlates of psychiatric disorders.

Diagnosis and monitoring of psychiatric disorders rely heavily on subjective self-reports of clinical symptoms, which are complicated by the varying consistency of accounts reported by patients with an impaired mental state. Hence, more objective and quantifiable measures have been sought to provide clinicians with more robust methods to evaluate symptomology and track progression of disease in response to treatments. Owing to the shared origins of the retina and the brain, it has been suggested that changes in the retina may correlate with structural and functional changes in the brain. Vast improvements in retinal imaging, namely optical coherence tomography (OCT) and electrodiagnostic technology, have made it possible to investigate the eye at a microscopic level, allowing for the investigation of potential biomarkers in vivo. This review provides a summary of retinal biomarkers associated with schizophrenia, bipolar disorder and major depression, demonstrating how retinal biomarkers may be used to complement existing methods and provide structural markers of pathophysiological mechanisms that underpin brain dysfunction in psychiatric disorders.

Ophthalmic Research Lecture 2018: DARC as a Potential Surrogate Marker.

Glaucoma is a progressive, neurodegenerative disease that is increasing in prevalence worldwide. There is a need to develop ways in which to diagnose the disease sooner and more reliably in order to prevent irreversible visual loss and meet the growing demands on healthcare services. Research into neuroprotective therapies in glaucoma is lacking a reliable surrogate marker in order to show treatment efficacy in a meaningful and cost-effective manner. The detection of apoptosing retinal cells (DARC) is a new technique that has promise in providing a solution to this unmet clinical need. Multiple animal studies have demonstrated its use as a biomarker in quantifying the effect of retinal neuroprotection methods, and it has recently been translated into humans in phase I and II trials, with phase I demonstrating the visualisation of individual apoptosing retinal cells in healthy and glaucomatous patients, with good safety and tolerability. The future for this technique will now be identifying disease-specific characteristics of human disease that can be used in order to provide us with a much-needed surrogate marker in the field of retinal neurodegeneration.

Retinal correlates of neurological disorders.

Considering the retina as an extension of the brain provides a platform from which to study diseases of the nervous system. Taking advantage of the clear optical media of the eye and ever-increasing resolution of modern imaging techniques, retinal morphology can now be visualized at a cellular level in vivo. This has provided a multitude of possible biomarkers and investigative surrogates that may be used to identify, monitor and study diseases until now limited to the brain. In many neurodegenerative conditions, early diagnosis is often very challenging due to the lack of tests with high sensitivity and specificity, but, once made, opens the door to patients accessing the correct treatment that can potentially improve functional outcomes. Using retinal biomarkers in vivo as an additional diagnostic tool may help overcome the need for invasive tests and histological specimens, and offers the opportunity to longitudinally monitor individuals over time. This review aims to summarise retinal biomarkers associated with a range of neurological conditions including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and prion diseases from a clinical perspective. By comparing their similarities and differences according to primary pathological processes, we hope to show how retinal correlates can aid clinical decisions, and accelerate the study of this rapidly developing area of research.

Real-Time Imaging of Retinal Ganglion Cell Apoptosis.

Monitoring real-time apoptosis in-vivo is an unmet need of neurodegeneration science, both in clinical and research settings. For patients, earlier diagnosis before the onset of symptoms provides a window of time in which to instigate treatment. For researchers, being able to objectively monitor the rates of underlying degenerative processes at a cellular level provides a biomarker with which to test novel therapeutics. The DARC (Detection of Apoptosing Retinal Cells) project has developed a minimally invasive method using fluorescent annexin A5 to detect rates of apoptosis in retinal ganglion cells, the key pathological process in glaucoma. Numerous animal studies have used DARC to show efficacy of novel, pressure-independent treatment strategies in models of glaucoma and other conditions where retinal apoptosis is reported, including Alzheimer’s disease. This may forge exciting new links in the clinical science of treating both cognitive and visual decline. Human trials are now underway, successfully demonstrating the safety and efficacy of the technique to differentiate patients with progressive neurodegeneration from healthy individuals. We review the current perspectives on retinal ganglion cell apoptosis, the way in which this can be imaged, and the exciting advantages that these future methods hold in store.

Annexins in Glaucoma.

Glaucoma is one of the leading causes of irreversible visual loss, which has been estimated to affect 3.5% of those over 40 years old and projected to affect a total of 112 million people by 2040. Such a dramatic increase in affected patients demonstrates the need for continual improvement in the way we diagnose and treat this condition. Annexin A5 is a 36 kDa protein that is ubiquitously expressed in humans and is studied as an indicator of apoptosis in several fields. This molecule has a high calcium-dependent affinity for phosphatidylserine, a cell membrane phospholipid externalized to the outer cell membrane in early apoptosis. The DARC (Detection of Apoptosing Retinal Cells) project uses fluorescently-labelled annexin A5 to assess glaucomatous degeneration, the inherent process of which is the apoptosis of retinal ganglion cells. Furthermore, this project has conducted investigation of the retinal apoptosis in the neurodegenerative conditions of the eye and brain. In this present study, we summarized the use of annexin A5 as a marker of apoptosis in the eye. We also relayed the progress of the DARC project, developing real-time imaging of retinal ganglion cell apoptosis in vivo from the experimental models of disease and identifying mechanisms underlying neurodegeneration and its treatments, which has been applied to the first human clinical trials. DARC has potential as a biomarker in neurodegeneration, especially in the research of novel treatments, and could be a useful tool for the diagnosis and monitoring of glaucoma.

Comparison of Central Corneal Thickness Between Fourier-Domain OCT, Very High-Frequency Digital Ultrasound, and Scheimpflug Imaging Systems.

PURPOSE: To compare corneal thickness measurements between three imaging systems. METHODS: In this retrospective study of 81 virgin and 58 post-laser refractive surgery corneas, central and minimum corneal thickness were measured using optical coherence tomography (OCT), very high-frequency digital ultrasound (VHF digital ultrasound), and a Scheimpflug imaging system. Agreement between methods was analyzed using mean differences (bias) (OCT - VHF digital ultrasound, OCT - Scheimpflug, VHF digital ultrasound - Scheimpflug) and Bland-Altman analysis with 95% limits of agreement (LoA). RESULTS: Virgin cornea mean central corneal thickness was 508.3 ± 33.2 µm (range: 434 to 588 µm) for OCT, 512.7 ± 32.2 µm (range: 440 to 587 µm) for VHF digital ultrasound, and 530.2 ± 32.6 µm (range: 463 to 612 µm) for Scheimpflug imaging. OCT and VHF digital ultrasound showed the closest agreement with a bias of -4.37 µm, 95% LoA ±12.6 µm. Least agreement was between OCT and Scheimpflug imaging with a bias of -21.9 µm, 95% LoA ±20.7 µm. Bias between VHF digital ultrasound and Scheimpflug imaging was -17.5 µm, 95% LoA ±19.0 µm. In post-laser refractive surgery corneas, mean central corneal thickness was 417.9 ± 47.1 µm (range: 342 to 557 µm) for OCT, 426.3 ± 47.1 µm (range: 363 to 563 µm) for VHF digital ultrasound, and 437.0 ± 48.5 µm (range: 359 to 571 µm) for Scheimpflug imaging. Closest agreement was between OCT and VHF digital ultrasound with a bias of -8.45 µm, 95% LoA ±13.2 µm. Least agreement was between OCT and Scheimpflug imaging with a bias of -19.2 µm, 95% LoA ±19.2 µm. Bias between VHF digital ultrasound and Scheimpflug imaging was -10.7 µm, 95% LoA ±20.0 µm. No relationship was observed between difference in central corneal thickness measurements and mean central corneal thickness. Results were similar for minimum corneal thickness. CONCLUSIONS: Central and minimum corneal thickness was measured thinnest by OCT and thickest by Scheimpflug imaging in both groups. A clinically significant bias existed between Scheimpflug imaging and the other two modalities.

Comparison of Corneal Epithelial Thickness Measurement Between Fourier-Domain OCT and Very High-Frequency Digital Ultrasound.

PURPOSE: To compare measurements of corneal epithelial thickness using optical coherence tomography (OCT) and very high-frequency digital ultrasound (VHFDU). METHODS: Retrospective analysis of 189 virgin corneas and 175 post-laser refractive surgery (LRS) corneas that had corneal epithelial thickness measurement with RTVue Fourier-domain OCT (Optovue, Inc., Fremont, CA) (tear film included) and Artemis VHFDU (ArcScan Inc., Morrison, CO) (tear film excluded). Averages were calculated for the central 2-mm diameter zone and for two further concentric annuli of 1.5- and 0.5-mm width, each divided into eight sectors. Agreement was analyzed by mean difference (OCT - VHFDU), 95% limits of agreement (LoA) (1.96 standard deviation of the difference), and Bland-Altman analysis. RESULTS: In virgin epithelium, mean central thickness was 53.4 ± 3.20 µm (range: 46 to 62 µm) with OCT and 54.1 ± 2.96 µm (range: 48 to 61 µm) with VHFDU; OCT measured thinnest in 70% with a mean difference of -0.71 µm (95% LoA of ± 3.94 µm, P < .001). In post-LRS epithelium, mean central thickness was 57.9 ± 6.08 µm (range: 42 to 77 µm) with OCT and 60.5 ± 6.47 µm (range: 42 to 79 µm) with VHFDU; OCT measured thinnest in 88%, with a mean difference of -2.48 µm (95% LoA of ± 5.33 µm, P < .001). A larger difference between methods was more common with thicker epithelium. CONCLUSIONS: Corneal epithelial thickness measurements using OCT were found to be slightly thinner than for VHFDU. In contrast to VHFDU, OCT measurement includes the tear film, so the true difference is probably approximately 4 µm more than reported. The difference was greatest inferiorly and higher for post-LRS eyes and in thicker epithelium.