Macular Telangiectasia Type 2: A Classification System Using MultiModal Imaging MacTel Project Report Number 10.

Purpose: To develop a severity classification for macular telangiectasia type 2 (MacTel) disease using multimodal imaging. Design: An algorithm was used on data from a prospective natural history study of MacTel for classification development. Subjects: A total of 1733 participants enrolled in an international natural history study of MacTel. Methods: The Classification and Regression Trees (CART), a predictive nonparametric algorithm used in machine learning, analyzed the features of the multimodal imaging important for the development of a classification, including reading center gradings of the following digital images: stereoscopic color and red-free fundus photographs, fluorescein angiographic images, fundus autofluorescence images, and spectral-domain (SD)-OCT images. Regression models that used least square method created a decision tree using features of the ocular images into different categories of disease severity. Main Outcome Measures: The primary target of interest for the algorithm development by CART was the change in best-corrected visual acuity (BCVA) at baseline for the right and left eyes. These analyses using the algorithm were repeated for the BCVA obtained at the last study visit of the natural history study for the right and left eyes. Results: The CART analyses demonstrated 3 important features from the multimodal imaging for the classification: OCT hyper-reflectivity, pigment, and ellipsoid zone loss. By combining these 3 features (as absent, present, noncentral involvement, and central involvement of the macula), a 7-step scale was created, ranging from excellent to poor visual acuity. At grade 0, 3 features are not present. At the most severe grade, pigment and exudative neovascularization are present. To further validate the classification, using the Generalized Estimating Equation regression models, analyses for the annual relative risk of progression over a period of 5 years for vision loss and for progression along the scale were performed. Conclusions: This analysis using the data from current imaging modalities in participants followed in the MacTel natural history study informed a classification for MacTel disease severity featuring variables from SD-OCT. This classification is designed to provide better communications to other clinicians, researchers, and patients. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Outreach screening to address demographic and economic barriers to diabetic retinopathy care in rural China.

IMPORTANCE: Poor access to existing care for diabetic retinopathy (DR) limits effectiveness of proven treatments. OBJECTIVES: We examined whether outreach screening in rural China improves equity of access. DESIGN, SETTING AND PARTICIPANTS: We compared prevalence of female sex, age > = 65 years, primary education or below, and requiring referral care for DR between three cohorts with diabetes examined for DR in neighboring areas of Guangdong, China: passive case detection at secondary-level hospitals (n = 193); persons screened during primary-level DR outreach (n = 182); and individuals with newly- or previously-diagnosed diabetes in a population survey (n = 579). The latter reflected the "ideal" reach of a screening program. RESULTS: Compared to the population cohort, passive case detection reached fewer women (50·8% vs. 62·3%, p = 0·006), older adults (37·8% vs. 51·3%, p < 0·001), and less-educated persons (39·9% vs. 89·6%, p < 0·001). Outreach screening, compared to passive case detection, improved representation of the elderly (49·5% vs. 37·8%, p = 0·03) and less-educated (70·3% vs. 39·9%, p<0·001). The proportion of women (59.8% vs 62.3%, P>0.300) and persons aged > = 65 years (49.5% vs 51.3%, p = 0.723) in the outreach screening and population cohorts did not differ significantly. Prevalence of requiring referral care for DR was significantly higher in the outreach screening cohort (28·0%) than the population (14·0%) and passive case detection cohorts (7·3%, p<0·001 for both). CONCLUSIONS AND RELEVANCE: Primary-level outreach screening improves access for the poorly-educated and elderly, and removes gender inequity in access to DR care in this setting, while also identifying more severely-affected patients than case finding in hospital.

State of the art spatial visualization of the response of neovascularisation to anti-vascular endothelial growth factor therapy.

PURPOSE: To visualize the mode of action of anti-vascular endothelial growth factor (anti-VEGFs) therapy on retinal neovascularization (RNV) in a patient with macular telangiectasia (MacTel) type 2 using a detailed three-dimensional data environment. OBSERVATION: A 60-year-old man presented with visual acuity loss and was diagnosed with MacTel type 2. Fluorescein angiography was not possible for safety reasons because of a history of severe reaction to fluorescein dye at his referring hospital. Optical coherence tomography angiography (OCTA) imaging revealed new retinal neovascular membranes (RNV) in the macula of both eyes. A marked reduction in the size of the RNV in both eyes was evident on volume-rendered three-dimensional OCTA retinal imaging after the first anti-VEGF injection. CONCLUSION AND IMPORTANCE: The ability to directly observe the effect of anti-VEGF injections on a RNV using three-dimensional OCTA was successfully demonstrated. This can be useful in patients with previous allergic and potentially lethal complications to fluorescein. In addition, enhanced three-dimensional spatial display of RNV leads to a greater understanding of the perfusion profile and the anatomical changes that occur in ocular neovascularization relative to surrounding tissue. This has the potential to provide insight into the pathobiology of angiogenesis.

Long-term vision outcomes for patients with albinism and diabetic retinopathy.

PURPOSE: Albinism defines a group of genetic diseases which result from disordered melanin biosynthesis. Proliferative diabetic retinopathy (PDR) results from poorly controlled type 1 or 2 diabetes mellitus (DM) and can lead to blindness due to progressive neovascularisation. However, the treatment of PDR in patients with ocular/oculocutaneous albinism may be more challenging. In this study, we compared a group of patients with albinism and PDR, to a group with albinism and diabetes mellitus but no PDR, to examine the long-term implications. METHODS: Retrospective observational study included all patients with ocular albinism (OA) or oculocutaneous albinism (OCA) and DM who presented at a single specialist centre. Participants were allocated into either group 1 (eyes with PDR) or group 2 (all eyes without PDR). Statistical analysis was performed using SPSS V26.0. Between-group differences were investigated. RESULTS: Outcome data was available for 5 eyes from 3 participants in group 1 and 26 eyes from 13 participants in group 2. Despite interventions, a large and significant difference in vision at follow-up was observed between group 1 and group 2 (mean change in visual acuity: 1.11 (± 1.00) versus - 0.15 (± 0.46), respectively; p = < 0.0001). CONCLUSION: PDR is associated with poor long-term prognosis despite interventions for patients with albinism. Those without PDR appear to maintain stable vision. Alternative treatments for PDR and its complications may be required in this population. Measures to prevent the development of diabetic eye disease and progression towards PDR should be employed at an early stage.

Re-evaluating diabetic papillopathy using optical coherence tomography and inner retinal sublayer analysis.

BACKGROUND/OBJECTIVES: To re-evaluate diabetic papillopathy using optical coherence tomography (OCT) for quantitative analysis of the peripapillary retinal nerve fibre layer (pRNFL), macular ganglion cell layer (mGCL) and inner nuclear layer (mINL) thickness. SUBJECTS/METHODS: In this retrospective observational case series between June 2008 and July 2019 at Moorfields Eye hospital, 24 eyes of 22 patients with diabetes and optic disc swelling with confirmed diagnosis of NAION or diabetic papillopathy by neuro-ophthalmological assessment were included for evaluation of the pRNFL, mGCL and mINL thicknesses after resolution of optic disc swelling. RESULTS: The mean age of included patients was 56.5 (standard deviation (SD) ± 14.85) years with a mean follow-up duration of 216 days. Thinning of pRNFL (mean: 66.26, SD ± 31.80 µm) and mGCL (mean volume: 0.27 mm3, SD ± 0.09) were observed in either group during follow-up, the mINL volume showed no thinning with 0.39 ± 0.05 mm3. The mean decrease in visual acuity was 4.13 (SD ± 14.27) ETDRS letters with a strong correlation between mGCL thickness and visual acuity (rho 0.74, p < 0.001). CONCLUSION: After resolution of acute optic disc swelling, atrophy of pRNFL and mGCL became apparent in all cases of diabetic papillopathy and diabetic NAION, with preservation of mINL volumes. Analysis of OCT did not provide a clear diagnostic distinction between both entities. We suggest a diagnostic overlay with the degree of pRNFL and mGCL atrophy of prognostic relevance for poor visual acuity independent of the semantics of terminology.

Fundus Autofluorescence Imaging in Macular Telangiectasia Type 2: MacTel Study Report Number 9.

PURPOSE: To investigate the role of fundus autofluorescence (FAF) imaging in the diagnosis of macular telangiectasia type 2 (MacTel) and to describe disease-associated FAF patterns and their origin. DESIGN: Cross-sectional multicenter study METHODS: FAF images were collected from the multicenter MacTel Natural History Observation and Registry Study. In a first qualitative approach, common FAF phenotypes were defined and correlated with multimodal imaging. We then evaluated how many eyes showed FAF changes, and temporal vs nasal asymmetry of FAF changes was graded. Finally, 100 eyes of MacTel patients and 100 control eyes (50 normal eyes and 50 eyes with other macular diseases) were combined and 2 masked graders assessed the presence of MacTel based on FAF images alone. RESULTS: The study included 807 eyes of 420 patients (33 eyes were excluded owing to poor image quality). Loss of macular pigment, cystoid spaces, pigment plaques, neovascular membranes, and ectatic vascular changes commonly caused characteristic changes on FAF images. All MacTel patients had macular FAF changes in at least 1 eye. In 95% of eyes, these changes were more pronounced temporally than nasally. Common FAF patterns were increased (60%) and mixed/decreased FAF (38%) and/or visibility of vascular changes such as blunted vessels or ectatic capillaries (79%). Based on those features, high diagnostic performance was achieved for detection of the disease based on FAF alone (Youden index up to 0.91). CONCLUSIONS: The study demonstrates that MacTel is consistently associated with disease-specific changes on FAF imaging. Those changes are typically more pronounced in the temporal parafovea.

Identification of genetic factors influencing metabolic dysregulation and retinal support for MacTel, a retinal disorder.

Macular Telangiectasia Type 2 (MacTel) is a rare degenerative retinal disease with complex genetic architecture. We performed a genome-wide association study on 1,067 MacTel patients and 3,799 controls, which identified eight novel genome-wide significant loci (p < 5 × 10-8), and confirmed all three previously reported loci. Using MAGMA, eQTL and transcriptome-wide association analysis, we prioritised 48 genes implicated in serine-glycine biosynthesis, metabolite transport, and retinal vasculature and thickness. Mendelian randomization indicated a likely causative role of serine (FDR = 3.9 × 10-47) and glycine depletion (FDR = 0.006) as well as alanine abundance (FDR = 0.009). Polygenic risk scoring achieved an accuracy of 0.74 and was associated in UKBiobank with retinal damage (p = 0.009). This represents the largest genetic study on MacTel to date and further highlights genetically-induced systemic and tissue-specific metabolic dysregulation in MacTel patients, which impinges on retinal health.

Quantification of Key Retinal Features in Early and Late Age-Related Macular Degeneration Using Deep Learning.

PURPOSE: We sought to develop and validate a deep learning model for segmentation of 13 features associated with neovascular and atrophic age-related macular degeneration (AMD). DESIGN: Development and validation of a deep-learning model for feature segmentation. METHODS: Data for model development were obtained from 307 optical coherence tomography volumes. Eight experienced graders manually delineated all abnormalities in 2712 B-scans. A deep neural network was trained with these data to perform voxel-level segmentation of the 13 most common abnormalities (features). For evaluation, 112 B-scans from 112 patients with a diagnosis of neovascular AMD were annotated by 4 independent observers. The main outcome measures were Dice score, intraclass correlation coefficient, and free-response receiver operating characteristic curve. RESULTS: On 11 of 13 features, the model obtained a mean Dice score of 0.63 ± 0.15, compared with 0.61 ± 0.17 for the observers. The mean intraclass correlation coefficient for the model was 0.66 ± 0.22, compared with 0.62 ± 0.21 for the observers. Two features were not evaluated quantitatively because of a lack of data. Free-response receiver operating characteristic analysis demonstrated that the model scored similar or higher sensitivity per false positives compared with the observers. CONCLUSIONS: The quality of the automatic segmentation matches that of experienced graders for most features, exceeding human performance for some features. The quantified parameters provided by the model can be used in the current clinical routine and open possibilities for further research into treatment response outside clinical trials.

Systemic lipid dysregulation is a risk factor for macular neurodegenerative disease.

Macular Telangiectasia type 2 (MacTel) is an uncommon bilateral retinal disease, in which glial cell and photoreceptor degeneration leads to central vision loss. The causative disease mechanism is largely unknown, and no treatment is currently available. A previous study found variants in genes associated with glycine-serine metabolism (PSPH, PHGDH and CPS1) to be associated with MacTel, and showed low levels of glycine and serine in the serum of MacTel patients. Recently, a causative role of deoxysphingolipids in MacTel disease has been established. However, little is known about possible other metabolic dysregulation. Here we used a global metabolomics platform in a case-control study to comprehensively profile serum from 60 MacTel patients and 58 controls. Analysis of the data, using innovative computational approaches, revealed a detailed, disease-associated metabolic profile with broad changes in multiple metabolic pathways. This included alterations in the levels of several metabolites that are directly or indirectly linked to glycine-serine metabolism, further validating our previous genetic findings. We also found changes unrelated to PSPH, PHGDH and CPS1 activity. Most pronounced, levels of several lipid groups were altered, with increased phosphatidylethanolamines being the most affected lipid group. Assessing correlations between different metabolites across our samples revealed putative functional connections. Correlations between phosphatidylethanolamines and sphingomyelin, and glycine-serine and sphingomyelin, observed in controls, were reduced in MacTel patients, suggesting metabolic re-wiring of sphingomyelin metabolism in MacTel patients. Our findings provide novel insights into metabolic changes associated with MacTel and implicate altered lipid metabolism as a contributor to this retinal neurodegenerative disease.

Macular Telangiectasia Type 2: Visual Acuity, Disease End Stage, and the MacTel Area: MacTel Project Report Number 8.

PURPOSE: To report the visual acuity measures from the macular telangiectasia type 2 (MacTel) registry and to investigate and describe phenotypic findings in eyes with substantial vision loss resulting from MacTel. DESIGN: Cross-sectional multicenter study. PARTICIPANTS: Participants in the MacTel Natural History Observation Registration Study. METHODS: Best-corrected visual acuity (BCVA) data, retinal imaging data, and clinical data were accessed from the MacTel Study databases in May 2019. MAIN OUTCOME MEASURES: Frequency distribution of BCVA and its relationship to age; morphologic changes in eyes with very late disease stages, defined by a BCVA of 20/200 or worse; average retinal thickness of macular subfields on OCT; and dimensions of the area affected by MacTel (i.e., the MacTel area). RESULTS: Best-corrected visual acuity was 20/50 or worse in 37.3% and 20/200 or worse in 3.8% of 4449 eyes of 2248 patients; 18.4% and 0.7% of all patients showed bilateral BCVA of 20/50 or worse and 20/200 or worse, respectively. Asymmetry between right and left eyes was present (median BCVA, 71 letters vs. 74 letters), a finding supported by more advanced morphologic changes in right eyes. Participant age correlated with BCVA, but the effect size was small. If a neovascularization or macular hole were present, bilateral occurrence was frequent (33% or 17%, respectively), and BCVA was better than 20/200 (79% or 78%, respectively) or 20/50 or better (26% or 13%, respectively). Eyes with advanced disease (BCVA, ≤20/200) showed the following characteristics: (1) atrophy of the foveal photoreceptor layer with or without associated subretinal fibrosis; (2) an affected area, termed MacTel area, limited to a horizontal diameter not exceeding the distance between the temporal optic disc margin and foveal center, and the vertical diameter not exceeding approximately 0.8 times this distance (exceptions were eyes with large active or inactive neovascular membranes); (3) reduced retinal thickness measures within the MacTel area; and (4) less frequent retinal greying and more frequent hyperpigmentations compared with eyes that have better BCVA. CONCLUSIONS: Severe vision loss is rare in MacTel and is related to photoreceptor atrophy in most people. Results indicate disease asymmetry with slightly worse vision and more advanced disease manifestation in right eyes. MacTel-related neurodegeneration does not spread beyond the limits of the MacTel area.

High-Resolution In Vivo Fundus Angiography using a Nonadaptive Optics Imaging System.

PURPOSE: We provide a proof of concept for the detailed characterization of retinal capillary features and surrounding photoreceptor mosaic using a customized nonadaptive optics angiography imaging system. METHODS: High-resolution fluorescein angiography (FFA) and/or indocyanine green angiography (ICGA) images were obtained using a modified Heidelberg retina angiograph (HRA2) device with a reduced scan angle enabling 3° field of view. Colocalized images of the photoreceptor mosaic also were captured in vivo using the same instrument. Visibility of vascular subbranches were compared between high-resolution images and conventional fundus angiography (FA) with a 30° field of view. RESULTS: High-resolution angiographic and infrared images (3° × 3° field of view, a 10-fold magnification) were obtained in 10 participants. These included seven patients with various retinal diseases, including myopic degeneration, diabetic retinopathy, macular telangiectasia, and central serous chorioretinopathy, as well as three healthy controls. Images of the retinal vasculature down to the capillary level were obtained on angiography with the ability to visualize a mean 1.2 levels more subbranches compared to conventional FA. In addition, imaging of the photoreceptor cone mosaic, to a sufficient resolution to calculate cone density, was possible. Movement of blood cells within the vasculature also was discernible on infrared videography. CONCLUSIONS: This exploratory study demonstrates that fast high-resolution angiography and cone visualization is feasible using a commercially available imaging system. TRANSLATIONAL RELEVANCE: This offers potential to better understand the relationship between the retinal neurovascular system in health and disease and the timing of therapeutic interventions in disease states.

Estimating Retinal Sensitivity Using Optical Coherence Tomography With Deep-Learning Algorithms in Macular Telangiectasia Type 2.

Importance: As currently used, microperimetry is a burdensome clinical testing modality for testing retinal sensitivity requiring long testing times and trained technicians. Objective: To create a deep-learning network that could directly estimate function from structure de novo to provide an en face high-resolution map of estimated retinal sensitivity. Design, Setting, and Participants: A cross-sectional imaging study using data collected between January 1, 2016, and November 30, 2017, from the Natural History Observation and Registry of macular telangiectasia type 2 (MacTel) evaluated 38 participants with confirmed MacTel from 2 centers. Main Outcomes and Measures: Mean absolute error of estimated compared with observed retinal sensitivity. Observed retinal sensitivity was obtained with fundus-controlled perimetry (microperimetry). Estimates of retinal sensitivity were made with deep-learning models that learned on superpositions of high-resolution optical coherence tomography (OCT) scans and microperimetry results. Those predictions were used to create high-density en face sensitivity maps of the macula. Training, validation, and test sets were segregated at the patient level. Results: A total of 2499 microperimetry sensitivities were mapped onto 1708 OCT B-scans from 63 eyes of 38 patients (mean [SD] age, 74.3 [9.7] years; 15 men [39.5%]). The numbers of examples for our algorithm were 67 899 (103 053 after data augmentation) for training, 1695 for validation, and 1212 for testing. Mean absolute error results were 4.51 dB (95% CI, 4.36-4.65 dB) when using linear regression and 3.66 dB (95% CI, 3.53-3.78 dB) when using the LeNet model. Using a 49.9 million-variable deep-learning model, a mean absolute error of 3.36 dB (95% CI, 3.25-3.48 dB) of retinal sensitivity for validation and test was achieved. Correlation showed a high degree of agreement (Pearson correlation r = 0.78). By paired Wilcoxon rank sum test, our model significantly outperformed these 2 baseline models (P < .001). Conclusions and Relevance: High-resolution en face maps of estimated retinal sensitivities were created in eyes with MacTel. The maps were of unequalled resolution compared with microperimetry and were able to correctly delineate functionally healthy and impaired retina. This model may be useful to monitor structural and functional disease progression and has potential as an objective surrogate outcome measure in investigational trials.

COMPARING FUNDUS FLUORESCEIN ANGIOGRAPHY AND SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN THE EVALUATION OF DIABETIC MACULAR PERFUSION.

PURPOSE: To compare fundus fluorescein angiography (FFA) and swept-source optical coherence tomography angiography (SS-OCTA) in the evaluation of macular perfusion in diabetic patients. METHODS: Forty-one eyes (21 diabetic patients) seen at Moorfields Eye Hospital (London) over a 1-month interval underwent color fundus photography, FFA, and SS-OCTA imaging of the capillary superficial plexus using 2 different protocols: 3 × 3 mm and 4.5 × 4.5 mm. Quantitative assessment (foveal avascular zone diameters and area), qualitative analysis (macroscopic and microscopic levels) and Early Treatment Diabetic Retinopathy Study diabetic macular ischemia grading were performed. Artifacts were recorded. Intraclass correlation coefficients and weighted kappa values were calculated. RESULTS: Mean (SD) foveal avascular zone area was 0.695 (0.52) mm on FFA, 0.627 (0.54) mm on SS-OCTA 3 × 3 and 0.701 (0.54) mm on SS-OCTA 4.5 × 4.5 protocol. Intraclass correlation coefficients showed good agreement between FFA and SS-OCTA for both vertical diameter and foveal avascular zone area measurements. The agreement between SS-OCTA 3 × 3 and 4.5 × 4.5 was good for all quantitative measurements. Weighted kappa for diabetic macular ischemia grading showed low to fair agreement between FFA and SS-OCTA, whereas the agreement was good between two different SS-OCTA protocols. CONCLUSION: Swept-source OCTA is a reproducible technique in the assessment of macular perfusion in diabetic patients with special regards to foveal avascular zone analysis. The agreement with FFA is limited especially for diabetic macular ischemia grading. Fundus fluorescein angiography is more sensitive in identifying microaneurysms.

United Kingdom Diabetic Retinopathy Electronic Medical Record (UK DR EMR) Users Group: report 4, real-world data on the impact of deprivation on the presentation of diabetic eye disease at hospital services.

AIM: To assess the impact of deprivation on diabetic retinopathy presentation and related treatment interventions, as observed within the UK hospital eye service. METHODS: This is a multicentre, national diabetic retinopathy database study with anonymised data extraction across 22 centres from an electronic medical record system. The following were the inclusion criteria: all patients with diabetes and a recorded, structured diabetic retinopathy grade. The minimum data set included, for baseline, age and Index of Multiple Deprivation, based on residential postcode; and for all time points, visual acuity, ETDRS grading of retinopathy and maculopathy, and interventions (laser, intravitreal therapies and surgery). The main  outcome measures were (1) visual acuity and binocular visual state, and (2) presence of sight-threatening complications and need for early treatment. RESULTS: 79 775 patients met the inclusion criteria. Deprivation was associated with later presentation in patients with diabetic eye disease: the OR of being sight-impaired at entry into the hospital eye service (defined as 6/18 to better than 3/60 in the better seeing eye) was 1.29 (95% CI 1.20 to 1.39) for the most deprived decile vs 0.77 (95% CI 0.70 to 0.86) for the least deprived decile; the OR for being severely sight-impaired (3/60 or worse in the better seeing eye) was 1.17 (95% CI 0.90 to 1.55) for the most deprived decile vs 0.88 (95% CI 0.61 to 1.27) for the least deprived decile (reference=fifth decile in all cases). There is also variation in sight-threatening complications at presentation and treatment undertaken: the least deprived deciles had lower chance of having a tractional retinal detachment (OR=0.48 and 0.58 for deciles 9 and 10, 95% CI 0.24 to 0.90 and 0.29 to 1.09, respectively); in terms of accessing treatment, the rate of having a vitrectomy was lowest in the most deprived cohort (OR=0.34, 95% CI 0.19 to 0.58). CONCLUSIONS: This large real-world study suggests that first presentation at a hospital eye clinic with visual loss or sight-threatening diabetic eye disease is associated with deprivation. These initial hospital visits represent the first opportunities to receive treatment and to formally engage with support services. Such patients are more likely to be sight-impaired or severely sight-impaired at presentation, and may need additional resources to engage with the hospital eye services over complex treatment schedules.

Contrast sensitivity and visual acuity under low light conditions in macular telangiectasia type 2.

BACKGROUND/AIM: Macular pigment optical density (MPOD) is centrally depleted early on in macular telangiectasia type 2 (MacTel). Contrast sensitivity (CS) might be related to MPOD, and thus impaired in early MacTel. The effect of low luminance was assessed on both CS and best corrected visual acuity (BCVA). METHODS: This is a cross-sectional study. Pelli-Robson charts were used for CS testing at 1 m in photopic (110 lux) and mesopic (1 lux) conditions. BCVA was tested with ETDRS charts and low luminance visual acuity (LLVA) with a 2.0 log unit neutral density filter. MPOD was obtained with dual-wavelength autofluorescence. RESULTS: One hundred and three eyes of 52 patients with MacTel (mean±SD age 62.9±10.2, range 35-77) were compared with 34 healthy eyes of 17 controls (mean±SD age 65.2±7.4, range 53-78). CS was significantly lower in the eyes with MacTel. This impairment was higher in low light conditions (low light contrast sensitivity (LL-CS)). Eyes at the early stages of MacTel had significantly lower LL-CS than controls, but normal (photopic) CS. The results were similar but less pronounced for BCVA/LLVA. Decrease in CS was correlated with loss of MPOD. CONCLUSIONS: Low light conditions have a detrimental effect on visual performance in MacTel. Impaired CS might correlate with MPOD depletion as a pathognomonic finding in MacTel. Functional impairment might precede structural disintegration, indicating dysfunction at the cellular level. The applied tests might be useful as additional functional assessments in clinical routine and as outcome measures in future interventional clinical trials.

PERIPAPILLARY PACHYCHOROID SYNDROME.

PURPOSE: To describe the features of peripapillary pachychoroid syndrome (PPS), a novel pachychoroid disease spectrum (PDS) entity. METHODS: Medical records of 31 eyes (16 patients) with choroidal thickening associated with intraretinal and/or subretinal fluid in the nasal macula extending from the disk were reviewed (patients with PPS). Choroidal thickness was compared with 2 age-matched cohorts: typical PDS (17 eyes with central serous chorioretinopathy or pachychoroid neovasculopathy) and 19 normal eyes. RESULTS: The patients with PPS were 81% men aged 71 ± 7 years. Peripapillary pachychoroid syndrome eyes displayed thicker nasal versus temporal macular choroids, unlike PDS eyes with thicker temporal macular choroids (P < 0.0001). Peripapillary intraretinal and/or subretinal fluid was often overlying dilated Haller layer vessels (pachyvessels). Fundus autofluorescence and fluorescein angiography illustrated peripapillary pigmentary mottling without focal leakage. Most PPS eyes (70%) exhibited other PDS findings including serous pigment epithelial detachment or gravitational tracks. Indocyanine green angiography illustrated dilated peripapillary pachyvessels and choroidal hyperpermeability. The disk was usually crowded, with edema noted in 4/31 (13%) eyes and mild late fluorescein disk leakage identified in half of the cases. Choroidal folds (77%), short axial lengths (39% less than 23 mm), and hyperopia (86%) were common. CONCLUSION: Peripapillary pachychoroid syndrome is a distinct PDS variant, in which peripapillary choroidal thickening is associated with nasal macular intraretinal and/or subretinal fluid and occasional disk edema. Recognition of PPS is important to distinguish it from disorders with overlapping features such as posterior uveitis and neuro-ophthalmologic conditions.

EFFECT OF DARK ADAPTATION AND BLEACHING ON BLUE LIGHT REFLECTANCE IMAGING IN MACULAR TELANGIECTASIA TYPE 2.

PURPOSE: In patients with macular telangiectasia Type 2, blue light reflectance imaging reveals an oval, parafoveal area in the macula that has increased reflectance compared with its surrounding. Here, we examine how dark adaptation and photobleaching can affect the blue light reflectance imaging pattern. METHODS: Prospective study of patients with macular telangiectasia enrolled in the MacTel Natural History Observation Study. After dark adaptation, a sequence of images was obtained with a confocal scanning laser ophthalmoscope at 488 nm. Change of reflectance patterns was analyzed over time. RESULTS: Eighteen eyes from 16 patients were analyzed. Initially, increased reflectivity in the parafoveal area resulted in higher gray values compared with the paramacular surrounding on blue light reflectance imaging. The difference between parafoveal and paramacular reflectance intensity decreased steadily during imaging, from 17.7 gray-value units (95% confidence interval: 12.1-23.2) down to 2.8 (95% confidence interval: -0.8 to 6.5) after around 30 seconds, and recovered after 5 minutes of dark adaptation. CONCLUSION: A bleaching effect was evident in our study. Understanding these changes is important for both diagnosis and assessment of blue light reflectance phenotype in patients with macular telangiectasia and could also provide further insights into the pathophysiology of this disease.

ELECTROPHYSIOLOGICAL CHARACTERIZATION OF MACULAR TELANGIECTASIA TYPE 2 AND STRUCTURE-FUNCTION CORRELATION.

PURPOSE: To investigate the electrophysiological features of macular telangiectasia Type 2 and their relationship to structure as determined by optical coherence tomography imaging. METHODS: Forty-two eyes from 21 patients enrolled in the Macular Telangiectasia Natural History Observation Study were reviewed. All patients had full-field and pattern electroretinography (ERG; PERG) with some patients additionally having multifocal electroretinography (mfERG; N = 15) or electrooculography (N = 12). Multiple linear regression modeling assessed the relationship between the ellipsoid zone break size on optical coherence tomography and the central mfERG response. RESULTS: Full-field ERG and electrooculography were normal in all eyes. Six eyes (14%) from five patients had subnormal PERG P50 amplitudes. Twenty-two of 30 eyes (73%) had reduced central or paracentral stimulus on mfERG. There was a significant correlation between ellipsoid zone break size and both the P1 amplitude (R = 0.37, P = 0.002) and P1:N1 ratio (R = 0.32, P = 0.002) of the central response on mfERG. CONCLUSION: The electrophysiological findings in macular telangiectasia Type 2 are those of localized central dysfunction and are consistent with the structural data available from imaging and histologic studies. The ellipsoid zone break size correlates with mfERG reduction. The reduced mfERG P1:N1 ratio is consistent with inner retinal dysfunction.