Imaging and Diagnostics

Imaging and Diagnostics Publications

Salongcay RP, Aquino LAC, Salva CMG, Saunar AV, Alog GP, Sun JK, Peto T, Silva PS. COMPARISON OF HANDHELD RETINAL IMAGING WITH ETDRS 7-STANDARD FIELD PHOTOGRAPHY FOR DIABETIC RETINOPATHY AND DIABETIC MACULAR EDEMA. Ophthalmol Retina 2022;Abstract
PURPOSE: To compare nonmydriatic and mydriatic handheld retinal imaging with standard ETDRS 7-field color fundus photography (ETDRS photos) for the assessment of diabetic retinopathy (DR) and diabetic macular edema (DME). DESIGN: Prospective, comparative, instrument validation study SUBJECTS: 225 eyes from 116 patients with diabetes mellitus METHODS: Following a standardized protocol, nonmydriatic and mydriatic images were acquired using handheld retinal cameras [Nonmydriatic (NM): Aurora (AUNM), Smartscope (SSNM), RetinaVue-700 (RVNM); Mydriatic (MD): Aurora (AUMD), Smartscope (SSMD), RetinaVue-700 (RVMD), iNview (NVMD)] and dilated ETDRS photos. Grading was performed at a centralized reading center using the International Clinical Classification for DR and DME. Kappa statistics [simple (K), weighted (Kw)] assessed the level of agreement for DR and DME. Sensitivity and specificity were calculated for any DR, referable DR (refDR) and vision-threatening DR (vtDR). MAIN OUTCOME MEASURES: Agreement for DR and DME, sensitivity and specificity for any DR, refDR and vtDR, ungradable rates RESULTS: Severity by ETDRS photos: no DR 33.3%, mild NPDR 20.4%, moderate 14.2%, severe in 11.6%, proliferative DR 20.4%; no DME 68.0%, DME 9.3%, ciDME 17.3%, ungradable 5.3%. For nonmydriatic handheld retinal imaging, Kw was 0.70 to 0.73 for DR and 0.76 to 0.83 for DME. For mydriatic handheld retinal imaging, Kw was 0.68 to 0.75 for DR and 0.77 to 0.91 for DME. Thresholds for sensitivity (0.80) and specificity (0.95) were met by SSNM, AUMD and RVMD for anyDR, and by AUMD and RVMD for refDR. Thresholds for sensitivity and specificity were met by AUMD and RVMD for DME. Nonmydriatic and Mydriatic ungradable rate for DR was 15.1% to 38.3% and 0% to 33.8%, respectively. CONCLUSIONS: Following standardized protocols, nonmydriatic and mydriatic handheld retinal imaging devices have substantial agreement levels for DR and DME. With mydriasis, not all handheld retinal imaging devices meet standards for sensitivity and specificity in identifying any DR and refDR. None of the handheld devices met the established 95% specificity for vtDR, suggesting that lower referral thresholds should be used if handheld devices must be utilized. When using handheld devices, the ungradable rate is significantly reduced with mydriasis and DME sensitivity thresholds are only achieved following dilation.
Naninck T, Kahlaoui N, Lemaitre J, Maisonnasse P, De Mori A, Pascal Q, Contreras V, Marlin R, Relouzat F, Delache B, Hérate C, Aldon Y, van Gils M, Zabaleta N, Tsong Fang RH, Bosquet N, Sanders RW, Vandenberghe LH, Chapon C, Le Grand R. Computed tomography and [18F]-FDG PET imaging provide additional readouts for COVID-19 pathogenesis and therapies evaluation in non-human primates. iScience 2022;25(4):104101.Abstract
Non-human primates (NHPs) are particularly relevant as preclinical models for SARS-CoV-2 infection and nuclear imaging may represent a valuable tool for monitoring infection in this species. We investigated the benefit of computed X-ray tomography (CT) and [18F]-FDG positron emission tomography (PET) to monitor the early phase of the disease in a large cohort (n = 76) of SARS-CoV-2 infected macaques. Following infection, animals showed mild COVID-19 symptoms including typical lung lesions. CT scores at the acute phase reflect the heterogeneity of lung burden following infection. Moreover, [18F]-FDG PET revealed that FDG uptake was significantly higher in the lungs, nasal cavities, lung-draining lymph nodes, and spleen of NHPs by 5 days postinfection compared to pre-infection levels, indicating early local inflammation. The comparison of CT and PET data from previous COVID-19 treatments or vaccines we tested in NHP, to this large cohort of untreated animals demonstrated the value of in vivo imaging in preclinical trials.
Zekavat SM, Sekimitsu S, Ye Y, Raghu V, Zhao H, Elze T, Segrè AV, Wiggs JL, Natarajan P, Del Priore L, Zebardast N, Wang JC. Photoreceptor layer thinning is an early biomarker for age-related macular degeneration: Epidemiological and genetic evidence from UK Biobank optical coherence tomography data. Ophthalmology 2022;Abstract
OBJECTIVE: Despite widespread use of optical coherence tomography (OCT), an early-stage imaging biomarker for age-related macular degeneration (AMD) has not been identified. Pathophysiologically, the timing of drusen accumulation in relation to photoreceptor degeneration in AMD remains unclear, as are the inherited genetic variants contributing to these processes. Here, we jointly analyzed OCT, electronic health record, and genomic data to characterize the time sequence of changes in retinal layer thicknesses in AMD, as well as epidemiological and genetic associations between retinal layer thicknesses and AMD. DESIGN: Cohort study PARTICIPANTS: 44,823 UK Biobank individuals (enrollment ages 40-70y, 54% female, median 10y follow-up). METHODS: The Topcon Advanced Boundary Segmentation algorithm was used for retinal layer segmentation. We associated 9 retinal layer thicknesses with prevalent AMD (present at enrollment) in a logistic regression model, and with incident AMD (diagnosed after enrollment) in a Cox proportional hazards model. Next, we associated AMD-associated genetic alleles, individually and as a polygenic risk score (PRS), with retinal layer thicknesses. All analyses were adjusted for age, age2, sex, smoking status, and principal components of ancestry. MAIN OUTCOME MEASURES: Prevalent and incident AMD RESULTS: Photoreceptor segment (PS) thinning was observed throughout the lifespan of individuals analyzed, while retinal pigment epithelium and Bruch's membrane complex (RPE+BM) thickening started after age 57y. Each standard deviation (SD) of PS thinning and RPE+BM thickening were associated with incident AMD (PS: HR 1.35, 95% CI 1.23-1.47, P=3.7x10-11; RPE+BM: HR 1.14, 95% CI 1.06-1.22, P=0.00024). The AMD PRS was associated with PS thinning (Beta -0.21 SD per 2-fold genetically increased risk of AMD, 95% CI -0.23 to -0.19, P=2.8x10-74), and its association with RPE+BM was U-shaped (thinning with AMD PRS<92nd percentile and thickening with AMD PRS>92nd percentile). The loci with strongest support for genetic correlation were AMD risk-raising variants CFH:rs570618-T, CFH:10922109-C, and ARMS2/HTRA1:rs3750846-C on PS thinning, and SYN3/TIMP3:rs5754227-T on RPE+BM thickening. CONCLUSIONS: Epidemiologically, PS thinning precedes RPE+BM thickening by decades, and is the retinal layer most strongly predictive of future AMD risk. Genetically, AMD risk variants are associated with decreased PS thickness. Overall, these findings support PS thinning as an early-stage biomarker for future AMD development.
Guzman Aparicio MA, Chen TC. New views on three-dimensional imaging technologies for glaucoma: an overview. Curr Opin Ophthalmol 2022;33(2):103-111.Abstract
PURPOSE OF REVIEW: To summarize the literature on three-dimensional (3D) technological advances in ophthalmology, the quantitative methods associated with this, and their improved ability to help detect glaucoma disease progression. RECENT FINDINGS: Improvements in measuring glaucomatous structural changes are the result of dual innovations in optical coherence tomography (OCT) imaging technology and in associated quantitative software. SUMMARY: Compared with two-dimensional (2D) OCT parameters, newer 3D parameters provide more data and fewer artifacts.
Bannai D, Adhan I, Katz R, Kim LA, Keshavan M, Miller JB, Lizano P. Quantifying Retinal Microvascular Morphology in Schizophrenia Using Swept-Source Optical Coherence Tomography Angiography. Schizophr Bull 2022;48(1):80-89.Abstract
BACKGROUND: Retinovascular changes are reported on fundus imaging in schizophrenia (SZ). This is the first study to use swept-source optical coherence tomography angiography (OCT-A) to comprehensively examine retinal microvascular changes in SZ. METHODS: This study included 30 patients with SZ/schizoaffective disorder (8 early and 15 chronic) and 22 healthy controls (HCs). All assessments were performed at Beth Israel Deaconess Medical Center and Massachusetts Eye and Ear. All participants underwent swept-source OCT-A of right (oculus dextrus [OD]) and left (oculus sinister [OS]) eye, clinical, and cognitive assessments. Macular OCT-A images (6 × 6 mm) were collected with the DRI Topcon Triton for superficial, deep, and choriocapillaris vascular regions. Microvasculature was quantified using vessel density (VD), skeletonized vessel density (SVD), fractal dimension (FD), and vessel diameter index (VDI). RESULTS: Twenty-one HCs and 26 SZ subjects were included. Compared to HCs, SZ patients demonstrated higher overall OD superficial SVD, OD choriocapillaris VD, and OD choriocapillaris SVD, which were primarily observed in the central, central and outer superior, and central and outer inferior/superior, respectively. Early-course SZ subjects had significantly higher OD superficial VD, OD choriocapillaris SVD, and OD choriocapillaris FD compared to matched HCs. Higher bilateral (OU) superficial VD correlated with lower Positive and Negative Syndrome Scale (PANSS) positive scores, and higher OU deep VDI was associated with higher PANSS negative scores. CONCLUSIONS AND RELEVANCE: These results suggest the presence of microvascular dysfunction associated with early-stage SZ. Clinical associations with microvascular alterations further implicate this hypothesis, with higher measures being associated with worse symptom severity and functioning in early stages and with lower symptom severity and better functioning in later stages.
Wang JC, Lu Y, Sobrin L, Husain D. MULTIMODAL IMAGING IN ACUTE RETINAL NECROSIS PRESENTING WITH MACULAR INVOLVEMENT. Retin Cases Brief Rep 2022;16(3):347-350.Abstract
PURPOSE: To report an unusual case of early macular necrosis in acute retinal necrosis and its features on multimodal imaging. METHODS: Findings on fundus examination, laboratory workup, fluorescein angiography, autofluorescence, optical coherence tomography, and optical coherence tomography angiography. RESULTS: A 31-year-old healthy woman presented with 1 week of photophobia and central scotoma of the right eye. Initial examination revealed vitritis, hyperemia of the optic disc, and a yellow-white macular lesion without any peripheral findings. Peripheral involvement was first noted only 4 days later. The patient was diagnosed with acute retinal necrosis secondary to varicella zoster virus and was successfully treated with intravitreal and oral antiviral medications. Optical coherence tomography imaging of the macular lesion showed involvement of both the inner and outer retina. Optical coherence tomography angiography revealed a large flow void in the choriocapillaris, which has not been previously demonstrated. CONCLUSION: Multimodal imaging offers valuable information in the evaluation of patients with acute retinal necrosis.
Inomata T, Nakamura M, Sung J, Midorikawa-Inomata A, Iwagami M, Fujio K, Akasaki Y, Okumura Y, Fujimoto K, Eguchi A, Miura M, Nagino K, Shokirova H, Zhu J, Kuwahara M, Hirosawa K, Dana R, Murakami A. Smartphone-based digital phenotyping for dry eye toward P4 medicine: a crowdsourced cross-sectional study. NPJ Digit Med 2021;4(1):171.Abstract
Multidimensional integrative data analysis of digital phenotyping is crucial for elucidating the pathologies of multifactorial and heterogeneous diseases, such as the dry eye (DE). This crowdsourced cross-sectional study explored a novel smartphone-based digital phenotyping strategy to stratify and visualize the heterogenous DE symptoms into distinct subgroups. Multidimensional integrative data were collected from 3,593 participants between November 2016 and September 2019. Dimension reduction via Uniform Manifold Approximation and Projection stratified the collected data into seven clusters of symptomatic DE. Symptom profiles and risk factors in each cluster were identified by hierarchical heatmaps and multivariate logistic regressions. Stratified DE subgroups were visualized by chord diagrams, co-occurrence networks, and Circos plot analyses to improve interpretability. Maximum blink interval was reduced in clusters 1, 2, and 5 compared to non-symptomatic DE. Clusters 1 and 5 had severe DE symptoms. A data-driven multidimensional analysis with digital phenotyping may establish predictive, preventive, personalized, and participatory medicine.
Sun JK, Josic K, Melia M, Glassman AR, Bailey C, Chalam KV, Chew EY, Cukras C, Grover S, Jaffe GJ, Lee R, Nielsen JS, Thompson DJS, Wiley HE, Ferris FL, Ferris FL. Conversion of Central Subfield Thickness Measurements of Diabetic Macular Edema Across Cirrus and Spectralis Optical Coherence Tomography Instruments. Transl Vis Sci Technol 2021;10(14):34.Abstract
Purpose: Develop equations to convert Cirrus central subfield thickness (CST) to Spectralis CST equivalents and vice versa in eyes with diabetic macular edema (DME). Methods: The DRCR Retina Network Protocol O data were split randomly to train (70% sample) and validate (30% sample) conversion equations. Data from an independent study (CADME) also validated the equations. Bland-Altman 95% limits of agreement between predicted and observed values evaluated the equations. Results: Protocol O included 374 CST scan pairs from 187 eyes (107 participants). The CADME study included 150 scan pairs of 37 eyes (37 participants). Proposed conversion equations are Spectralis = 40.78 + 0.95 × Cirrus and Cirrus = 1.82 + 0.94 × Spectralis regardless of age, sex, or CST. Predicted values were within 10% of observed values in 101 (90%) of Spectralis and 99 (88%) of Cirrus scans in the validation data; and in 136 (91%) of the Spectralis and 148 (99%) of the Cirrus scans in the CADME data. Adjusting for within-eye correlations, 95% of conversions are estimated to be within 17% (95% confidence interval, 14%-21%) of CST on Spectralis and within 22% (95% confidence interval, 18%-28%) of CST on Cirrus. Conclusions: Conversion equations developed in this study allow the harmonization of CST measurements for eyes with DME using a mix of current Cirrus and Spectralis device images. Translational Relevance: The CSTs measured on Cirrus and Spectralis devices are not directly comparable owing to outer boundary segmentation differences. Converting CST values across spectral domain optical coherence tomography instruments should benefit both clinical research and standard care efforts.
Cui Y, Zhu Y, Lu ES, Le R, Laíns I, Katz R, Wang JC, Garg I, Lu Y, Zeng R, Eliott D, Vavvas DG, Husain D, Miller JW, Kim LA, Wu DM, Miller JB. Widefield Swept-Source OCT Angiography Metrics Associated with the Development of Diabetic Vitreous Hemorrhage: A Prospective Study. Ophthalmology 2021;128(9):1312-1324.Abstract
PURPOSE: To investigate the association among widefield swept-source (SS) OCT angiography (OCTA) metrics and systemic parameters and vitreous hemorrhage (VH) occurrence in eyes with proliferative diabetic retinopathy (PDR). DESIGN: Prospective, observational study. PARTICIPANTS: Fifty-five eyes from 45 adults with PDR, with no history of VH, followed up for at least 3 months. METHODS: All patients underwent widefield SS OCTA (Montage 15 × 15 mm and high-definition (HD)-51 line scan) imaging. Images were evaluated independently by 2 graders for quantitative and qualitative widefield SS OCTA metrics defined a priori. Systemic and ocular parameters and widefield SS OCTA metrics were screened using least absolute shrinkage and selection operator and logistic or Cox regression for variable selection. Firth's bias-reduced logistic regression models (outcome, occurrence of VH) and Cox regression models (outcome, time to occurrence of VH) were used to identify parameters associated with VH occurrence. MAIN OUTCOME MEASURES: Occurrence of VH. RESULTS: Over a median follow-up of 363 days (range, 28-710 days), 13 of 55 PDR eyes (24%) demonstrated VH during the follow-up period. Presence of extensive neovascularizations (odds ratio, 8.05; 95% confidence interval [CI], 1.43-58.56; P = 0.02), defined as neovascularizations with total area of more than 4 disc diameters, and forward neovascularizations (odds ratio, 5.42; 95% CI, 1.26-35.16; P = 0.02) that traversed the posterior hyaloid face into the vitreous were associated with the occurrence of VH. The presence of flat neovascularizations (odds ratio, 0.25; 95% CI, 0.04-1.01; P = 0.05) confined to the posterior hyaloid face was associated with a lower risk of VH with borderline significance. Similarly, presence of extensive neovascularizations (hazard ratio, 18.24; 95% CI, 3.51-119.47; P < 0.001) and forward neovascularizations (hazard ratio, 9.60; 95% CI, 2.07-68.08; P = 0.002) was associated significantly with time to development of VH. CONCLUSIONS: Widefield SS OCTA is useful for evaluating neovascularizations and their relationship with the vitreous. The presence of forward and extensive neovascularizations was associated with the occurrence of VH in patients with PDR. Larger samples and longer follow-up are needed to verify the risk factors and imaging biomarkers for diabetic VH.
Moon JY, Garg I, Cui Y, Katz R, Zhu Y, Le R, Lu Y, Lu ES, Ludwig CA, Elze T, Wu DM, Eliott D, Miller JW, Kim LA, Husain D, Vavvas DG, Miller JB. Wide-field swept-source optical coherence tomography angiography in the assessment of retinal microvasculature and choroidal thickness in patients with myopia. Br J Ophthalmol 2021;Abstract
BACKGROUND/AIMS: Pathological myopia (PM) is a leading cause of blindness worldwide. We aimed to evaluate microvascular and chorioretinal changes in different stages of myopia with wide-field (WF) swept-source (SS) optical coherence tomography angiography (OCTA). METHODS: This prospective cross-sectional observational study included 186 eyes of 122 patients who had undergone imaging between November 2018 and October 2020. Vessel density (VD) and vessel skeletonised density (VSD) of superficial capillary plexus, deep capillary plexus and whole retina, as well as foveal avascular zone parameters, retinal thickness (RT) and choroidal thickness (CT), were calculated. RESULTS: This study evaluated 75 eyes of 48 patients with high myopia (HM), 43 eyes of 31 patients with mild to moderate myopia and 68 eyes of 53 age-matched controls. Controlling for age and the presence of systemic hypertension, we found that HM was associated with decrease in VD and VSD in all layers on 12×12 mm² scans. Furthermore, HM was associated with a VD and VSD decrease in every Early Treatment Diabetic Retinopathy Study grid, with a larger decrease temporally (βVD=-0.39, βVSD=-10.25, p<0.01). HM was associated with decreased RT and CT. Reduction in RT was outside the macular region, while reduction in CT was in the macular region. CONCLUSION: Using WF SS-OCTA, we identified reduction in microvasculature and structural changes associated with myopia. Decrease in VD and VSD was greater in the temporal quadrant, and reductions in RT and CT were uneven across the retina. Further work may help identify risk factors for the progression of PM and associated vision-threatening complications.
Bosque LE, Yamarino CR, Salcedo N, Schneier AJ, Gold RS, Blumenfeld LC, Hunter DG. Evaluation of the blinq vision scanner for detection of amblyopia and strabismus. J AAPOS 2021;Abstract
PURPOSE: To report the results of a clinical study designed to evaluate the accuracy of the blinq pediatric vision scanner, which detects amblyopia and strabismus directly by means of retinal polarization scanning, unlike other vision screening devices, which infer possible disease based on detection of refractive risk factors. METHODS: Subjects 1-20 years of age were prospectively enrolled in this cross-sectional diagnostic accuracy study with planned enrollment of 200. All enrolled subjects were tested by individuals masked to the diagnosis, followed by complete ophthalmologic examination by pediatric ophthalmologists masked to the screening result. Patients previously treated for amblyopia or strabismus were analyzed separately. RESULTS: The study cohort comprised 193 subjects, 53 of whom had been previously treated, leaving 140 treatment-naïve subjects, including 65 (46%) with amblyopia or strabismus, 11 (8%) with risk factors/suspected binocular vision deficit without amblyopia/strabismus, and 64 (46%) controls. Sensitivity was 100%, with all 66 patients with referral-warranted ocular disease referred. Five patients with intermittent strabismus receiving pass results were deemed "acceptable pass" when considering patient risk factors and amblyogenic potential. Specificity was 91%, with 7 incorrect referrals. Subanalysis of children aged 2-8 years (n = 92) provided similar results (sensitivity 100%; specificity 89%). CONCLUSIONS: In this study cohort, the blinq showed very high sensitivity and specificity for detecting referral-warranted amblyopia and strabismus. Implementation of the device in vision screening programs could lead to improved rates of disease detection and reduction in false referrals.
Currant H, Hysi P, Fitzgerald TW, Gharahkhani P, Bonnemaijer PWM, Senabouth A, Hewitt AW, and Consortium UKBEV, and Consortium UKBEV, Atan D, Aung T, Charng J, Choquet H, Craig J, Khaw PT, Klaver CCW, Kubo M, Ong J-S, Pasquale LR, Reisman CA, Daniszewski M, Powell JE, Pébay A, Simcoe MJ, Thiadens AAHJ, van Duijn CM, Yazar S, Jorgenson E, Macgregor S, Hammond CJ, Mackey DA, Wiggs JL, Foster PJ, Patel PJ, Birney E, Khawaja AP. Genetic variation affects morphological retinal phenotypes extracted from UK Biobank optical coherence tomography images. PLoS Genet 2021;17(5):e1009497.Abstract
Optical Coherence Tomography (OCT) enables non-invasive imaging of the retina and is used to diagnose and manage ophthalmic diseases including glaucoma. We present the first large-scale genome-wide association study of inner retinal morphology using phenotypes derived from OCT images of 31,434 UK Biobank participants. We identify 46 loci associated with thickness of the retinal nerve fibre layer or ganglion cell inner plexiform layer. Only one of these loci has been associated with glaucoma, and despite its clear role as a biomarker for the disease, Mendelian randomisation does not support inner retinal thickness being on the same genetic causal pathway as glaucoma. We extracted overall retinal thickness at the fovea, representative of foveal hypoplasia, with which three of the 46 SNPs were associated. We additionally associate these three loci with visual acuity. In contrast to the Mendelian causes of severe foveal hypoplasia, our results suggest a spectrum of foveal hypoplasia, in part genetically determined, with consequences on visual function.
da Cunha LP, Cavalcante Costa MAA, de Miranda HA, Reis Guimarães J, Aihara T, Ludwig CA, Rosenblatt T, Callaway NF, Pasricha M, Al-Moujahed A, Vail D, Ji MH, Kumm J, Moshfeghi DM. Comparison between wide-field digital imaging system and the red reflex test for universal newborn eye screening in Brazil. Acta Ophthalmol 2021;99(7):e1198-e1205.Abstract
PURPOSE: To compare neonatal eye screening using the red reflex test (RRT) versus the wide-field digital imaging (WFDI) system. METHODS: Prospective cohort study. Newborns (n = 380, 760 eyes) in the Maternity Ward of Irmandade Santa Casa de Misericórdia de São Paulo hospital from May to July 2014 underwent RRT by a paediatrician and WFDI performed by the authors. Wide-field digital imaging (WFDI) images were analysed by the authors. Validity of the paediatrician's RRT was assessed by unweighted kappa [κ] statistic, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: While WFDI showed abnormalities in 130 eyes (17.1%), RRT was only abnormal in 13 eyes (1.7%). Wide-field digital imaging (WFDI) detected treatable retina pathology that RRT missed including hyphema, CMV retinitis, FEVR and a vitreous haemorrhage. The sensitivity of the paediatrician's RRT to detect abnormalities was poor at 0.77% (95% confidence interval, CI, 0.02%-4.21%) with a PPV of only 7.69% (95% CI, 1.08%-38.85%). Overall, there was no agreement between screening modalities (κ = -0.02, 95% CI, -0.05 to 0.01). The number needed to screen to detect ocular abnormalities using WFDI was 5.9 newborns and to detect treatable abnormalities was 76 newborns. CONCLUSION: While RRT detects gross abnormalities that preclude visualization of the retina (i.e. media opacities and very large tumours), only WFDI consistently detects subtle treatable retina and optic nerve pathology. With a higher sensitivity than the current gold standard, universal WFDI allows for early detection and management of potentially blinding ophthalmic disease missed by RRT.
Hanumunthadu D, Lescrauwaet B, Jaffe M, Sadda SV, Wiecek E, Hubschman JP, Patel PJ. Clinical Update on Metamorphopsia: Epidemiology, Diagnosis and Imaging. Curr Eye Res 2021;46(12):1777-1791.Abstract
Purpose: To discuss the pathophysiology of metamorphopsia, its characterisation using retinal imaging and methods of assessment of patient symptoms and visual function.Methods: A literature search of electronic databases was performedResults: Metamorphopsia has commonly been associated with vitreomacular interface disorders (such as epiretinal membrane) and has also regularly been noted in diseases of the retina and choroid, particularly age-related macular degeneration and central serous chorioretinopathy. Developments in optical coherence tomography retinal imaging have enabled improved imaging of the foveal microstructure and have led to the localisation of the pathophysiology of metamorphopsia within the retinal layers of the macula. Alteration of alignment of inner and outer retinal layers at various retinal loci has been identified using multimodal imaging in patients with metamorphopsia in a range of conditions. Although the Amsler Grid assessment of metamorphopsia is a useful clinical indicator, new emerging methods of metamorphopsia assessment with psychophysical tests such as M-CHARTS and preferential hyperacuity perimetry, have been developed.Conclusions: It appears that there is a complex relationship between visual acuity and metamorphopsia symptoms that vary between retinal conditions. Although metamorphopsia has traditionally been challenging to measure in the clinic, advances in technology promise more robust, easy-to-use tests. It is possible that home assessment of metamorphopsia, particularly in conditions such as age-related macular degeneration, may help to guide the need for further clinic evaluation and consideration of treatment.

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