Optical coherence tomography angiography in the diagnosis of ocular disease.

Clinical imaging provided by optical coherence tomography (OCT) and its variant, OCT-angiography (OCT-A), has revolutionised eyecare practice. The imaging techniques allow for the identification and quantification of ocular structures, supporting the diagnosis and prognosis of eye disease. In this review, an overview of the usefulness of OCT-A imaging in the diagnosis and management of a range of ocular conditions is provided when used in isolation or in combination with other imaging modalities and measures of visual function (visual field results). OCT-A imaging has the capacity to identify and quantify ocular vasculature non-invasively, thereby assisting the clinician in the diagnosis or to determine the efficacy of intervention in ocular conditions impacting retinal vasculature. Thus, additional clinically useful information can be obtained in eye diseases involving conditions such as those impacting retinal vessel occlusion, in diabetic retinopathy, inherited retinal dystrophy, age-related macular degeneration, choroidal neovascularisation and optic nerve disorders. Through a clinical case series, various ocular conditions are reviewed, and the impact of OCT-A imaging is discussed. Although OCT-A imaging has great promise and is already used in clinical management, there is a lack of set standards to characterise altered vascular features in disease and consequently for prognostication, primarily due to a lack of large-scale clinical trials and variability in OCT-A algorithms when generating quantitative parameters.

Frontloading visual field tests detect earlier mean deviation progression when applied to real-world-derived early-stage glaucoma data.

PURPOSE: To examine the diagnostic accuracy of performing two (frontloaded) versus one (clinical standard) visual field (VF) test per visit for detecting the progression of early glaucoma in data derived from clinical populations. METHODS: A computer simulation model was used to follow the VFs of 10,000 glaucoma patients (derived from two cohorts: Heijl et al., Swedish cohort; and Chauhan et al., Canadian Glaucoma Study [CGS]) over a 10-year period to identify patients whose mean deviation (MD) progression was detected. Core data (baseline MD and progression rates) were extracted from two studies in clinical cohorts of glaucoma, which were modulated using SITA-Faster variability characteristics from previous work. Additional variables included follow-up intervals (six-monthly or yearly) and rates of perimetric data loss for any reason (0%, 15% and 30%). The main outcome measures were the proportions of progressors detected. RESULTS: When the Swedish cohort was reviewed six-monthly, the frontloaded strategy detected more progressors compared to the non-frontloaded method up to years 8, 9 and 10 of follow-up for 0%, 15% and 30% data loss conditions. The time required to detect 50% of cases was 1.0-1.5 years less for frontloading compared to non-frontloading. At 4 years, frontloading increased detection by 26.7%, 28.7% and 32.4% for 0%, 15% and 30% data loss conditions, respectively. Where both techniques detected progression, frontloading detected progressors earlier compared to the non-frontloaded strategy (78.5%-81.5% and by 1.0-1.3 years when reviewed six-monthly; 81%-82.9% and by 1.2-2.1 years when reviewed yearly). Accordingly, these patients had less severe MD scores (six-monthly review: 0.63-1.67 dB 'saved'; yearly review: 1.10-2.87 dB). The differences increased with higher rates of data loss. Similar tendencies were noted when applied to the CGS cohort. CONCLUSIONS: Frontloaded VFs applied to clinical distributions of MD and progression led to earlier detection of early glaucoma progression.

Comparing a head-mounted virtual reality perimeter and the Humphrey Field Analyzer for visual field testing in healthy and glaucoma patients.

PURPOSE: To compare clinical visual field outputs in glaucoma and healthy patients returned by the Humphrey Field Analyzer (HFA) and virtual reality (Virtual Field, VF) perimetry. METHODS: One eye of 54 glaucoma patients and 41 healthy subjects was prospectively tested (three times each in random order) using the HFA and VF perimeters (24-2 test grids). We extracted and compared global indices (mean deviation [MD] and pattern standard deviation [PSD]), pointwise sensitivity (and calculated 'equivalent' sensitivity after accounting for differences in background luminance) and pointwise defects. Bland-Altman (mean difference [Mdiff ] and 95% limits of agreement [LoA]) and intraclass correlation analyses were performed. RESULTS: The VF test was shorter (by 76 s) and had lower fixation losses (by 0.08) and false-positive rate (by 0.01) compared to the HFA (all p < 0.0001). Intraclass correlations were 0.86, 0.82 and 0.47 for MD, PSD and pointwise sensitivity between devices, respectively. Test-retest variability was higher for VF (Mdiff 0.3 dB, LoA -7.6 to 8.2 dB) compared to the HFA (Mdiff -0.3 dB, LoA -6.4 to 5.9 dB), indicating greater test-retest variability. When using each device's underlying normative database, the HFA detected, on average, 7 more defects (at the p < 0.05 level) out of the 52 test locations compared to this iteration of VF in the glaucoma cohort. CONCLUSIONS: Virtual Field returns global results that are correlated with the HFA, but pointwise sensitivities were more variable. Differences in test-retest variability and defect detection by its current normative database raise questions about the widespread adoption of VF in lieu of the HFA.

Evaluating the clinical relevance and reliability of outer retinal band length on optical coherence tomography in retinal disease: a cross-sectional study.

OBJECTIVES: Hyper-reflective outer retinal band (HORB) disruptions are reported across a range of retinal disease, yet a reliable, easily implemented assessment method and thorough evaluation of their association to retinal disease is lacking. The purpose of the study was to assess the reliability of using magnitude estimation to evaluate HORB length and determine its association to visual acuity and retinal disease. DESIGN: Cross-sectional, retrospective study. SETTING: Patients attending a secondary eye care clinic in Sydney, Australia. PARTICIPANTS: 2039 unique consecutive patients were screened for inclusion between 2 November and 18 January 2021, and 600 were included in the study population. Patients were included if they were referred from primary care, presented for an initial, comprehensive eye examination during the study period, imaged with optical coherence tomography during their visit and over 18 years of age. PRIMARY OUTCOME: Reliability of HORB length estimations and associations to clinical outcomes. RESULTS: Intragrader (intraclass correlation coefficient, ICCfovea=0.81; ICCworst=0.91) and intergrader (ICCfovea=0.78-0.79; ICCworst=0.75-0.88) agreement of HORB length was good to excellent. HORB length was significantly associated with age (p<0.001, ß=-0.22 to -0.24) and refractive error (p<0.001, ß=0.12-0.16) at all B-scan locations. Visual acuity (p=0.001, ß=-0.13) was associated with the primary outcome for foveal B-scans and eccentricity (p=0.002, ß=-0.13) and device type (p=0.002, ß=0.13) for non-foveal B-scans. Glaucoma was associated with HORB length on univariate analysis (p=0.05-0.06, ß=-0.08); however, multivariate analysis revealed no significant association between HORB length and retinal disease. CONCLUSION: HORB length is reliably assessed using magnitude estimation and may be useful as a surrogate biomarker of visual acuity. Several factors affect HORB length estimations, which may contribute to the lack of association to retinal disease and highlights the need for covariable adjustment when examining HORB disruptions.

Ocular ischaemia: signs, symptoms, and clinical considerations for primary eye care practitioners.

Ischaemic stroke is a major disease burden as well as a leading cause of death. Early signs of ischaemic stroke can manifest in the eye, placing primary eyecare practitioners in an important position to identify patients at risk of ischaemic stroke and initiate suitable referral pathways. The vascular supply to the brain is reviewed with reference to vision including the various retinal signs and ocular symptoms associated with transient ischaemic attacks and ischaemic stroke. Using a range of clinical cases, the diverse clinical presentations of retinal embolic events, as well as other forms of vascular occlusion, are highlighted and the underlying pathophysiology is discussed. A succinct scheme for the assessment and management of ischaemic events for primary eye care practitioners is provided.

Clinical outcomes of the Centre for Eye Health: an intra-professional optometry-led collaborative eye care clinic in Australia.

Clinical relevance: This novel clinical model is the first of its kind in Australia and was designed to help reduce unnecessary referrals into overburdened public systems by utilising pre-existing community-based resources.Background: The Centre for Eye Health (CFEH) is an intra-professional optometry-led care clinic offering an alternative pathway to traditional ophthalmology-based pathways (public hospital clinics or private practices) for 'at-risk' patients requiring ocular imaging, diagnostic and management services. This study evaluates the CFEH integrated eye-care model in the identification of chronic eye diseases within the community.Methods: A retrospective random clinical audit of over 750 medical records of patients referred to the CFEH between July 2016 and June 2019 was conducted. Demographics of patients, referral type, final diagnosis and recommended management plans were extracted from this subset. Clinic key performance indicators (referral turnaround time, and net cost per patient appointment) were also extracted.Results: Of the 755 referrals associated with the audited records, 77.4% resulted in the identification of patients with or at-risk of developing eye diseases with 73.5% of this cohort requiring ongoing monitoring at CFEH or referral to ophthalmology. Although the CFEH model is not designed to diagnose or manage acute conditions, 1.5% of patients in this pathway required same day ophthalmological or medical intervention. The cost per patient was equivalent to hospital eye departments costs.Conclusion: This integrated care pathway has the potential to reduce unnecessary referrals from optometrists to hospital ophthalmological service by offering a safe and effective alternate pathway. The majority of patients seen within this pathway were able to be monitored within optometry-led services. This is a unique clinical model utilising inter-professional referrals within optometry which has the potential to reduce preventable blindness within the community through the early detection of eye diseases.

Headaches related to latanoprost in open-angle glaucoma.

Clinical relevance: The existing notion that topical latanoprost can lead to symptoms of headaches by reporting three cases of headache symptoms that developed following instillation of latanoprost prescribed as first-line therapy for newly diagnosed primary open-angle glaucoma (POAG) is explored in this case series.Background: Prostaglandin analogues (PGAs) are often used as first-line treatment in the treatment of POAG. An uncommon and infrequently reported side effect of PGAs is headaches.Methods: A retrospective review of patient records was conducted on patients seen at the Centre for Eye Health between April 2016 and August 2017. Clinical findings, including outcomes following interventions such a punctal occlusion, as well as the proposed pharmacological mechanism underlying this phenomenon are presented and discussed.Results: Case 1 is a 62-year-old Caucasian male diagnosed with POAG and prescribed latanoprost in both eyes. At the follow-up visit, he reported waking up in with a dull throbbing headache following instillation of the eye drops the night before. Case 2 is a 58-year-old Asian male with POAG prescribed latanoprost to both eyes. Within a week, he developed symptoms of recurrent progressively worsening headaches post-instillation which persisted into the morning. Case 3 is a 75-year-old Caucasian male with POAG prescribed latanoprost for both eyes. He developed latanoprost sensitivity as well as headache symptoms associated with the eye drops which resolved followed its cessation. All patients reported initial symptoms of headaches associated with latanoprost use however the headaches were not persistent with intermittent punctal occlusion (cases 1 and 2) or intra-class drug rechallenge (case 3).Conclusion: Although there may be a yet-undiscovered link between a headache response and latanoprost, these cases call to question the pharmacological relationship between latanoprost and headache symptoms. A systemic approach to critically examine the pathophysiological link between pharmacological therapy and potential adverse effects is proposed.

The performance and confidence of clinicians in training in the analysis of ophthalmic images within a work-integrated teaching model.

PURPOSE: A fundamental clinical skill is the recognition of artefacts within the outputs of advanced imaging modalities. However, current teaching programmes of healthcare practitioners are becoming increasingly challenged to provide practical exposure within an already crowded curriculum. This study evaluates the impact of a novel work-integrated teaching model on the confidence and competence of clinicians in the use of optical coherence tomography (OCT) and the recognition of its artefacts. The outcomes were then used to develop a model to predict performance and guide teaching strategies. METHODS: We prospectively evaluated a 6-week clinical placement for final year optometry students within a diagnostic eye clinic in 2018-2020. Participants completed a quiz on the identification of common OCT artefacts and rated their confidence levels on key areas of OCT application using a five-point Likert scale. Both were completed before (pre-rotation) and after (post-rotation) the placement. The cohort was divided into two groups; the first group was used to assess the impact of the placement and derive the prediction model for post-placement performance, which was then validated against the second group. RESULTS: A significant improvement in detecting OCT imaging artefacts was seen upon completion of the placement, which was greater in participants with lower entry level performance. Across all OCT artefact subtypes, there was an improvement in detecting segmentation error, delineation error and media opacities. A model predicting post-placement student performance was developed using entry level knowledge base as the key dependent variable. Self-rated confidence improved across all domains of OCT application but was not found to be a direct predictor of actual performance. CONCLUSIONS: These results highlight the benefit of a work-integrated learning programme on both academic performance and confidence whilst identifying entry level knowledge base as the key variable predicting improvement. Tailored teaching incorporating entering knowledge is the best predictor of improvement during clinical placements. Integrating clinicians into a work-integrated setting with tailored teaching and comprehensive practical exposure can be an effective method for training future or current healthcare professionals.

Management of open-angle glaucoma by primary eye-care practitioners: toward a personalised medicine approach.

Glaucoma is the leading cause of irreversible blindness worldwide. As a chronic disease, glaucoma presents a significant burden to the individual, health-care provider and the health-care system. Currently, strategies for treating glaucoma are focused on lowering intraocular pressure, which is aimed at slowing or arresting disease progression over time. This is the only current accepted therapeutic strategy for glaucoma, and can be achieved using topical drugs, laser trabeculoplasty, filtration surgery or cyclodestructive techniques. The lowering of intraocular pressure has been well-supported by numerous large-scale seminal clinical trials in primary open-angle glaucoma, in both its early and advanced stages. Although such guidance remains current, in the last 10-years, there has been a significant evolution in preferred first-line therapies in the treatment of open-angle glaucoma with a resultant shift in practice patterns, particularly early in the course of the disease. These changes reflect both from the perspective of the doctor - in titrating the most effective and least risky treatment modality - and the perspective of the patient, in consenting to a treatment that preserves vision and results in minimal negative impact on quality of life. In this review, the most recent evidence regarding treatment modalities for early primary open-angle glaucoma is presented and an updated framework for management guidance is proposed.

Validation of a novel functional test for assessing metamorphopsia using epiretinal membranes as a model.

Current tests for assessing metamorphopsia do not account for confounders such as perceptual filling-in and spatial redundancy, which affect its sensitivity and repeatability. This proof-of-concept study aimed to assess the performance of a novel laboratory-based psychophysical test (Line Sag Test, LST) which addresses these issues for quantification of metamorphopsia in idiopathic epiretinal membranes. The LST quantifies perpendicular metamorphopsia at three eccentricities (3°, 6°, and 9°) along eight meridians (45° steps). Metamorphopsia was assessed using the LST and Amsler grid and the hit rates of both tests for detecting metamorphopsia were compared. Normal metamorphopsia scores using the LST did not differ significantly from 0 and fell within one step-size (p = 0.500). The LST detected significantly more cases of metamorphopsia than the Amsler grid (14/21 versus 3/21) (p = 0.003). Similarly, significantly more cases of visual distortions in asymptomatic iERMs were detected using the LST than the Amsler grid (11/18 versus 0/18) (p = 0.008). The LST has a higher hit rate compared to the Amsler grid (67% versus 14%). This work demonstrates a psychophysically-robust functional test addressing perceptual confounders is more sensitive for quantifying and localising metamorphopsia in macular disease, particularly in asymptomatic disease.

Multimodal imaging characteristics of congenital grouped hyper- and hypo-pigmented fundus lesions.

BACKGROUND: The imaging characteristics of congenital grouped pigmentation of the retinal pigment epithelium (CGP-RPE) and its non-pigmented variant - grouped congenital albinotic retinal pigment epithelial spots (GCARPES) are poorly defined in the literature. Our case series reports their multimodal imaging characteristics across a spectrum of presentations. METHODS: A retrospective review of patient records was conducted on patients seen at the Centre for Eye Health between January and December 2016. The multimodal imaging findings across four cases is described using optical coherence tomography (OCT), infrared imaging, ultra-widefield imaging, fundus photography and fundus autofluorescence (FAF). RESULTS: Case 1 is a 55-year-old female with a bilateral presentation of CGP-RPE showing typical features. Case 2 is a 28-year-old male with a classical presentation of GCARPES in the left eye. Case 3 is a 33-year-old female with unilateral CGP-RPE and an atypical solitary congenital hypertrophy of the retinal pigment epithelium (CHRPE) in the same eye. Case 4 is a unilateral presentation in an 11-year-old female with unusual characteristics. Ocular imaging characteristics of CGP-RPE lesions varied between patients: OCT showed visible RPE changes in cases 3 and 4 but not case 1. The pattern of FAF and infrared imaging also varied with most lesions displaying a pattern of hypo-autofluorescence, but some central lesions in case 3 exhibited hyper-autofluorescence. All lesions were visible with fundus photography. CONCLUSION: FAF can be helpful in alerting clinicians to the presence of lesions that may be difficult to visualise funduscopically and OCT can be helpful in differentiating between CGP-RPE and its variants from more sinister ocular conditions. All in all, these findings highlight the variable manifestation of CGP-RPE and its variants on multimodal imaging; the diagnosis of CGP-RPE and its variants should remain based on its characteristic funduscopic appearance.

Anterior Chamber Angle Evaluation Using Gonioscopy: Consistency and Agreement between Optometrists and Ophthalmologists.

SIGNIFICANCE: In our intermediate-tier glaucoma care clinic, we demonstrate fair to moderate agreement in gonioscopy examination between optometrists and ophthalmologists, but excellent agreement when considering open versus closed angles. We highlight the need for increased consistency in the evaluation and recording of angle status using gonioscopy. PURPOSE: The consistency of gonioscopy results obtained by different clinicians is not known but is important in moving toward practice modalities such as telemedicine and collaborative care clinics. The purpose of this study was to evaluate the description and concordance of gonioscopy results among different practitioners. METHODS: The medical records of 101 patients seen within a collaborative care glaucoma clinic who had undergone gonioscopic assessment by two clinicians (one optometrist and either one general ophthalmologist [n = 50] or one glaucoma specialist [n = 51]) were reviewed. The gonioscopy records were evaluated for their descriptions of deepest structure seen, trabecular pigmentation, iris configuration, and other features. These were compared between clinicians (optometrist vs. ophthalmologist) and against the final diagnosis. RESULTS: Overall, 51.9 and 59.8% of angles were graded identically in terms of deepest visible structure when comparing between optometrist versus general ophthalmologist and optometrist versus glaucoma specialist, respectively. The concordance increased when considering ±1 of the grade (67.4 and 78.5%, respectively), and agreement with the final diagnosis was high (>90%). Variations in angle grading other than naming structures were observed (2.0, 30, and 3.9% for optometrist, general ophthalmologist, and glaucoma specialist, respectively). Most of the time, trabecular pigmentation or iris configuration was not described. CONCLUSIONS: Fair to moderate concordance in gonioscopy was achieved between optometrists and ophthalmologists in a collaborative care clinic in which there is consistent feedback and clinical review. To move toward unified medical records and a telemedicine model, improved consistency of record keeping and angle description is required.

Remote Grading of the Anterior Chamber Angle Using Goniophotographs and Optical Coherence Tomography: Implications for Telemedicine or Virtual Clinics.

PURPOSE: To evaluate the agreement and accuracy of grading goniophotographs and anterior segment optical coherence tomography (AS-OCT) results for assessment of the anterior chamber angle, and elicit factors driving concordance between perceived grade and ground truth. METHODS: Three clinicians evaluated the goniophotographs and AS-OCT results of 75 patients. Graders' impressions of the angle grade, trabecular pigmentation, and iris contour were compared with the ground truth gonioscopic examination result when physically performed by a senior optometrist. Percentage agreement and kappa statistics were calculated. Binary logistic regression was used to elicit factors for accurate grading. RESULTS: Exact angle matches and binary (open or closed) evaluations were above guessing rate for all graders. There was a systematic bias toward underestimating the angle structure across all graders, especially at the superior angle, by approximately 1 ordinal unit. Kappa statistics showed fair-moderate agreement for exact (0.387-0.520) and binary (0.347-0.520) angle evaluations. Agreement was unchanged when using a multimodal approach (0.373-0.523). Factors driving concordance were primarily related to the extremes of the anterior chamber angle configuration (shallow or deep structures, and iris contour). However, prediction models did not fully explain the levels of concordance with the ground truth (maximum R 2 amongst models 0.177). CONCLUSIONS: Although moderate agreement between graders and ground truth could be obtained under binary evaluations, angle grades were generally underestimated. Factors affecting concordance were primarily the extremes of the ground truth angle and iris contour. TRANSLATIONAL RELEVANCE: We highlight factors affecting accuracy of grading goniophotography and AS-OCT images of the anterior chamber angle.

Optimising the Structure-Function Relationship at the Locus of Deficit in Retinal Disease.

Technologies such as optical coherence tomography have facilitated the visualization of anatomical tissues such as that of the retina. The availability of in vivo retinal anatomical data has led to the hypothesis that it may be able to accurately predict visual function from anatomical information. However, accurate determination of the structure-function relationship has remained elusive in part due to contributions of non-retinal sources of variability, thus imposing potential limitations in the fidelity of the relationship. Furthermore, differences in manifestation of functional loss due to different retinal loci of change (inner retina or outer retinal elements) have also been the subject of debate. Here, we assessed the application of a novel, more objective psychophysical paradigm to better characterize the relationship between functional and structural characteristics in the eye. Using ocular diseases with known loci of anatomical change (glaucoma, inner retinal loss; and retinitis pigmentosa, outer retinal loss), we compared conventional more subjective psychophysical techniques that may be contaminated by the presence of non-retinal sources of variability with our more objective approach. We show that stronger correlations between underlying retinal structure and visual function can be achieved across a breadth of anatomical change by using a more objective psychophysical paradigm. This was independent of the locus of structural loss (at the ganglion cells for glaucoma or photoreceptors for retinitis pigmentosa), highlighting the role of downstream retinal elements to serve as anatomical limiting factors for studying the structure-function relationship. By reducing the contribution of non-retinal sources of variability in psychophysical measurements, we herein provide a structure-function model with higher fidelity. This reinforces the need to carefully consider the psychophysical protocol when examining the structure-function relationship in sensory systems.

Differences in Static and Kinetic Perimetry Results are Eliminated in Retinal Disease when Psychophysical Procedures are Equated.

PURPOSE: We tested the hypothesis that clinical statokinetic dissociation (SKD, defined as the difference in sensitivity to static and kinetic stimuli) at the scotoma border in retinal disease is due to individual criterion bias and that SKD can be eliminated by equating the psychophysical procedures for testing static and kinetic stimulus detection. METHODS: Six subjects with glaucoma and six with retinitis pigmentosa (RP) were tested. Clinical procedures (standard automated perimetry [SAP] and manual kinetic perimetry [MKP]) were used to determine clinical SKD and the region of interest for laboratory-based testing. Two-way Method of Limits (MoL) was used to establish the isocontrast region at the scotoma border in glaucoma and RP subjects. Method of Constant Stimuli (MoCS) and a two-interval forced choice (2IFC) procedure then were used to present static or kinetic (inward or outward) stimuli at different eccentricities within the isocontrast region. The results were fitted with psychometric functions to determine threshold eccentricities. RESULTS: Clinical SKD was found in glaucoma and RP subjects, with variable magnitude among subjects, but significantly exceeding expected typical measurement variability. The resultant psychometric functions when using MoCS and 2IFC showed equal sensitivity to static and kinetic targets, thus eliminating SKD. CONCLUSIONS: Clinical SKD found using clinical techniques is due to methodologic differences and criterion bias, and is eliminated by using an equated and more objective psychophysical task, similar to normal subjects. TRANSLATIONAL RELEVANCE: Eliminating SKD using a psychophysical approach minimizing criterion bias suggests that it is not useful to distinguish between normal and diseased fields.

Neutralizing Peripheral Refraction Eliminates Refractive Scotomata in Tilted Disc Syndrome.

SIGNIFICANCE: We demonstrate that the visual field defects in patients with tilted disc syndrome can be reduced or eliminated by neutralizing the peripheral scotoma in the area of posterior retinal bowing, which may allow differentiation between a congenital anomaly and acquired pathology. PURPOSE: Tilted disc syndrome is a congenital and unchanging condition that may present with visual field defects mimicking loss seen in neurological diseases, such as transsynaptic retrograde degeneration. Our purpose was to systematically investigate the ability of a neutralized peripheral refraction to eliminate refractive visual field defects seen in tilted disc syndrome. This was compared with the same technique performed on patients with neurological deficits. METHODS: The Humphrey Field Analyzer was used to measure sensitivities across the 30-2 test grid in 14 patients with tilted disc syndrome using four refractive corrections: habitual near correction and with an additional -1.00, -2.00 or -3.00 D negative lens added as correction lenses. Peripheral refractive errors along the horizontal meridian were determined using peripheral retinoscopy and thus allowed calculation of residual peripheral refraction with different levels of refractive correction. Visual field defects were assessed qualitatively and quantitatively using sensitivities and probability scores in both patient groups. RESULTS: A smaller residual refractive error after the application of negative addition lenses correlated with improvement in visual field defects in terms of sensitivity and probability scores in patients with tilted disc syndrome. Patients with established neurological deficits (retrograde degeneration) showed improvement in sensitivities but not in probability scores. CONCLUSIONS: Neutralizing the refractive error at the region of posterior retinal bowing due to tilted disc syndrome reduces the apparent visual field defect. This may be a useful and rapid test to help differentiate between tilted disc syndrome and other pathological causes of visual field defects such as neurological deficits.

Retinal Thickness Changes throughout the Natural History of Drusen in Age-related Macular Degeneration.

SIGNIFICANCE: Drusen are associated with retinal thinning in age-related macular degeneration (AMD). These changes, however, have mostly been examined at single time points, ignoring the evolution of drusen from emergence to regression. Understanding the full breadth of retinal changes associated with drusen will improve understanding of disease pathogenesis. PURPOSE: The purpose of this study was to assess how the natural history of drusen affects retinal thickness, focusing on the photoreceptor and retinal pigment epithelium (RPE) layers. METHODS: Spectral domain optical coherence tomography of subjects with intermediate AMD (n = 50) who attended the Centre for Eye Health, Sydney, Australia, for two separate visits (476 ± 16 days between visits) was extracted. Scans were automatically segmented with manufacturer software then assessed for drusen that had emerged, grown, or regressed between visits. For each identified lesion, the thickness of each retinal layer at the drusen peak and at adjacent drusen-free areas (150 µm nasal and temporal to the druse) was compared between visits. RESULTS: Before drusen emergence, the RPE was significantly thicker at the drusen site (14.2 ± 2.6%) compared with neighboring drusen-free areas. There was a 71% sensitivity of RPE thickening predicting drusen emergence. Once drusen emerged, significant thinning of all outer retinal layers was observed, consistent with previous studies. Drusen growth was significantly correlated with thinning of the outer retina (r = -0.38, P < .001). Drusen regression resulted in outer retinal layers returning to thicknesses not significantly different from baseline. CONCLUSIONS: The natural history of drusen is associated with RPE thickening before drusen emergence, thinning of the outer nuclear layer as well as photoreceptor and RPE layers proportional to drusen growth, and return to baseline thickness after drusen regression. These findings have useful clinical applications, providing a potential marker for predicting drusen emergence for AMD prognostic and intervention studies and highlighting that areas of normal retinal thickness in AMD may be former sites of regressed drusen.