Self-Supervised Learning for Improved Optical Coherence Tomography Detection of Macular Telangiectasia Type 2.

Importance: Deep learning image analysis often depends on large, labeled datasets, which are difficult to obtain for rare diseases. Objective: To develop a self-supervised approach for automated classification of macular telangiectasia type 2 (MacTel) on optical coherence tomography (OCT) with limited labeled data. Design, Setting, and Participants: This was a retrospective comparative study. OCT images from May 2014 to May 2019 were collected by the Lowy Medical Research Institute, La Jolla, California, and the University of Washington, Seattle, from January 2016 to October 2022. Clinical diagnoses of patients with and without MacTel were confirmed by retina specialists. Data were analyzed from January to September 2023. Exposures: Two convolutional neural networks were pretrained using the Bootstrap Your Own Latent algorithm on unlabeled training data and fine-tuned with labeled training data to predict MacTel (self-supervised method). ResNet18 and ResNet50 models were also trained using all labeled data (supervised method). Main Outcomes and Measures: The ground truth yes vs no MacTel diagnosis is determined by retinal specialists based on spectral-domain OCT. The models' predictions were compared against human graders using accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), area under precision recall curve (AUPRC), and area under the receiver operating characteristic curve (AUROC). Uniform manifold approximation and projection was performed for dimension reduction and GradCAM visualizations for supervised and self-supervised methods. Results: A total of 2636 OCT scans from 780 patients with MacTel and 131 patients without MacTel were included from the MacTel Project (mean [SD] age, 60.8 [11.7] years; 63.8% female), and another 2564 from 1769 patients without MacTel from the University of Washington (mean [SD] age, 61.2 [18.1] years; 53.4% female). The self-supervised approach fine-tuned on 100% of the labeled training data with ResNet50 as the feature extractor performed the best, achieving an AUPRC of 0.971 (95% CI, 0.969-0.972), an AUROC of 0.970 (95% CI, 0.970-0.973), accuracy of 0.898%, sensitivity of 0.898, specificity of 0.949, PPV of 0.935, and NPV of 0.919. With only 419 OCT volumes (185 MacTel patients in 10% of labeled training dataset), the ResNet18 self-supervised model achieved comparable performance, with an AUPRC of 0.958 (95% CI, 0.957-0.960), an AUROC of 0.966 (95% CI, 0.964-0.967), and accuracy, sensitivity, specificity, PPV, and NPV of 90.2%, 0.884, 0.916, 0.896, and 0.906, respectively. The self-supervised models showed better agreement with the more experienced human expert graders. Conclusions and Relevance: The findings suggest that self-supervised learning may improve the accuracy of automated MacTel vs non-MacTel binary classification on OCT with limited labeled training data, and these approaches may be applicable to other rare diseases, although further research is warranted.

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.

Short-Term Efficacy and Safety Outcomes of Brolucizumab in the Real-Life Clinical Practice.

To report the early efficacy and safety outcomes of treatment with intravitreal injections of brolucizumab (IVT-B) in patients presenting neovascular age-related macular degeneration (nAMD) in a tertiary clinical setting. A retrospective case series of patients that received IVT-B with a minimum of two injections performed and at least 4 weeks of follow-up after last injection. Nineteen eyes of 19 patients were included. The number of IVT-B performed for the whole cohort was 58 injections; the mean number of IVT-B per patient was 3.0 ± 1.0 (range 2-6); the mean follow-up time was 14.4 ± 9.0 weeks. Mean baseline best-corrected visual acuity was 0.4 ± 0.4 logMAR and at the last follow-up was 0.4 ± 0.6 logMAR (p = 0.778). All eyes showed a reduction in retinal thickness, with the central macular thickness being 470 ± 151 µm at baseline and 360 ± 144 µm at the last follow-up (p = 0.001). Intra-retinal fluid was present at baseline in 12 eyes (63%) and in three eyes (16%) at the last follow-up (p = 0.065). Sub-retinal fluid was present at baseline in 17 eyes (89%) and at the last follow-up in three eyes (16%, p = 0.011). Pigment epithelium detachment was apparent in the 16 eyes (84%) at baseline and was still present in 14 eyes (73%, p = 0.811). One adverse event of intraocular inflammation was reported. In conclusion, our short-term experience showed that brolucizumab was highly effective in restoring the anatomy and in stabilizing the visual acuity of eyes with nAMD. Its safety profile should be evaluated carefully and needs further investigations.

Genetic disruption of serine biosynthesis is a key driver of macular telangiectasia type 2 aetiology and progression.

BACKGROUND: Macular telangiectasia type 2 (MacTel) is a rare, heritable and largely untreatable retinal disorder, often comorbid with diabetes. Genetic risk loci subtend retinal vascular calibre and glycine/serine/threonine metabolism genes. Serine deficiency may contribute to MacTel via neurotoxic deoxysphingolipid production; however, an independent vascular contribution is also suspected. Here, we use statistical genetics to dissect the causal mechanisms underpinning this complex disease. METHODS: We integrated genetic markers for MacTel, vascular and metabolic traits, and applied Mendelian randomisation and conditional and interaction genome-wide association analyses to discover the causal contributors to both disease and spatial retinal imaging sub-phenotypes. RESULTS: Genetically induced serine deficiency is the primary causal metabolic driver of disease occurrence and progression, with a lesser, but significant, causal contribution of type 2 diabetes genetic risk. Conversely, glycine, threonine and retinal vascular traits are unlikely to be causal for MacTel. Conditional regression analysis identified three novel disease loci independent of endogenous serine biosynthetic capacity. By aggregating spatial retinal phenotypes into endophenotypes, we demonstrate that SNPs constituting independent risk loci act via related endophenotypes. CONCLUSIONS: Follow-up studies after GWAS integrating publicly available data with deep phenotyping are still rare. Here, we describe such analysis, where we integrated retinal imaging data with MacTel and other traits genomics data to identify biochemical mechanisms likely causing this disorder. Our findings will aid in early diagnosis and accurate prognosis of MacTel and improve prospects for effective therapeutic intervention. Our integrative genetics approach also serves as a useful template for post-GWAS analyses in other disorders.

Progression characteristics of ellipsoid zone loss in macular telangiectasia type 2.

PURPOSE: To investigate the progression characteristics of ellipsoid zone (EZ) loss in eyes with macular telangiectasia type 2 (MacTel) as reflected by area and linear measurements, and their relevance for visual acuity. METHODS: Participants were selected from the MacTel Study cohort. Linear and area measurements of EZ loss were performed in Spectral-Domain Optical Coherence Tomograph (SD-OCT) volume scans. Progression characteristics and correlations between linear and area measurements were analysed using linear mixed effects models. RESULTS: A total of 134 eyes of 70 patients were included (85 eyes with follow-up, mean 4.7 years, range: 1.4-8 years). Ellipsoid zone (EZ) loss significantly progressed at a mean annual increment of 0.057 mm2 (p = 0.005). The progression rate was non-linear and interacted significantly with initial EZ lesion size indicating an exponential growth before reaching a plateau. There was a strong heterogeneity in area sizes between fellow eyes. EZ break length had a significant linear effect on EZ break area (b = 1.06, p < 0.001) and could predict it. The location of the EZ break had a significant impact on visual acuity. CONCLUSION: Ellipsoid zone (EZ) loss in MacTel has a non-linear progression characteristic, and its rate depends on area size at baseline, which must be taken into account at sample selection in clinical trials. Our results show a good correlation of linear and area measures of EZ loss and a segregation of best-corrected visual acuity by EZ location, which may help routine clinical practice.

Potential Effects of Hormone Therapy in Type 2 Idiopathic Macular Telangiectasia.

PURPOSE: To investigate the influence of hormone therapy with tamoxifen or estrogens on morphological changes in macular telangiectasia (MacTel) type 2 patients as revealed clinically in multiple imaging modalities. METHODS: Patients with a history of tamoxifen or estrogen use were selected from the cohort of the MacTel Study. A race-, age- and best-corrected visual acuity-matched group of MacTel participants not under hormone therapy served as the comparison group. The frequencies of typical features of the MacTel phenotype apparent in color fundus, red-free, fluorescein angiographic and optical coherence tomographic images were graded and analyzed statistically. RESULTS: Thirty-nine MacTel patients were included in the analyses, of whom 13 were receiving tamoxifen, 13 estrogens and 13 patients no hormone treatment. Patients treated with estrogens showed significantly fewer breaks in the ellipsoid zone on optical coherence tomography (7 eyes, 29.1%, vs. tamoxifen: 14 eyes, 53.8%, and vs. controls: 14 eyes, 53.8%, p = 0.04 in both analyses, Fisher exact test). Retinal crystalline deposits were significantly more frequent in patients receiving estrogens (12 eyes, 16.2%, vs. 2 eyes, 2.7%, p = 0.003, Fisher exact test). No significant between-group differences were apparent with regard to other features of the phenotype (extent of retinal low reflective spaces, late hyperfluorescence on fluorescein angiography or retinal thickness). CONCLUSIONS: Tamoxifen treatment does not seem to accentuate structural changes in patients with MacTel type 2. Treatment with estrogens may exhibit a neuroprotective effect as suggested by the decreased frequency of ellipsoid zone breaks in corresponding patients, although corroborative studies are warranted to confirm these exploratory data.

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.

CORRELATION OF CLINICAL AND STRUCTURAL PROGRESSION WITH VISUAL ACUITY LOSS IN MACULAR TELANGIECTASIA TYPE 2: MacTel Project Report No. 6-The MacTel Research Group.

PURPOSE: To evaluate progression of macular telangiectasia Type 2 lesions and their correlation with visual acuity. METHODS: An international multicenter prospective study with annual examinations including best-corrected visual acuity (BCVA), fundus photography, fluorescein angiography, and optical coherence tomography images graded centrally. Mixed models were used to estimate progression rates, and a generalized linear model to compute the relative risk of BCVA loss, loss of ellipsoid zone (EZ) reflectivity, development of pigment plaques, or neovascularization. RESULTS: One thousand and fourteen eyes of 507 participants were followed for 4.2 ± 1.6 years. Best-corrected visual acuity decreased 1.07 ± 0.05 letters (mean ± SE) per year. Of all eyes, 15% lost ≥15 letters after 5 years. Of the eyes without EZ loss, 76% developed a noncentral loss. Of the eyes with noncentral loss, 45% progressed to central EZ loss. The rate of BCVA loss in eyes with noncentral EZ loss at baseline was similar to eyes without EZ loss. The rate of BCVA loss was significantly higher in eyes with central EZ loss at baseline (-1.40 ± 0.14 letters, P < 0.001). CONCLUSION: Ellipsoid zone loss is frequently found in macular telangiectasia Type 2 and is an important structural component reflecting visual function. Its presence in the fovea significantly correlates with worse visual prognosis.

ABNORMAL RETINAL REFLECTIVITY TO SHORT-WAVELENGTH LIGHT IN TYPE 2 IDIOPATHIC MACULAR TELANGIECTASIA.

PURPOSE: Macular telangiectasia Type 2 (MacTel) is a bilateral, progressive, potentially blinding retinal disease characterized by vascular and neurodegenerative signs, including an increased parafoveal reflectivity to blue light. Our aim was to investigate the relationship of this sign with other signs of macular telangiectasia Type 2 in multiple imaging modalities. METHODS: Participants were selected from the MacTel Type 2 study, based on a confirmed diagnosis and the availability of images. The extent of signs in blue-light reflectance, fluorescein angiographic, optical coherence tomographic, and single- and dual-wavelength autofluorescence images were analyzed. RESULTS: A well-defined abnormality of the perifovea is demonstrated by dual-wavelength autofluorescence and blue-light reflectance in early disease. The agreement in area size of the abnormalities in dual-wavelength autofluorescence and in blue-light reflectance images was excellent: for right eyes: ρ = 0.917 (P < 0.0001, 95% confidence interval 0.855-0.954, n = 46) and for left eyes: ρ = 0.952 (P < 0.0001, 95% confidence interval 0.916-0.973, n = 49). Other changes are less extensive initially and expand later to occupy that area and do not extend beyond it. CONCLUSION: Our findings indicate that abnormal metabolic handling of luteal pigment and physical changes giving rise to increased reflectance are widespread in the macula throughout the natural history of the disease, precede other changes, and are relevant to early diagnosis.

CORRELATION OF STRUCTURAL AND FUNCTIONAL OUTCOME MEASURES IN A PHASE ONE TRIAL OF CILIARY NEUROTROPHIC FACTOR IN TYPE 2 IDIOPATHIC MACULAR TELANGIECTASIA.

PURPOSE: Macular telangiectasia Type 2 is a bilateral, progressive, potentially blinding retinal disease characterized by both vascular and neurodegenerative signs. Both the area of the break in the ellipsoid zone seen in "en face" optical coherence tomographic (OCT) images and microperimetric focal retinal sensitivity loss have been proposed as potential measures of progression in macular telangiectasia. The authors aimed to assess the characteristics and interrelationship of these structural and functional disease markers from the data collected in a phase one clinical trial of ciliary neurotrophic factor in macular telangiectasia. METHODS: Orthogonal topographic (en face) maps of the ellipsoid zone were generated from Heidelberg Spectralis OCT volume scans (15 × 10° area, 30-µm B-scan intervals) or Zeiss Cirrus HD-OCT 4000 512 × 128 cube scans. Mesopic microperimetry was performed on CenterVue MAIA perimeters, using a Goldmann III stimulus in a custom test grid. Structural and functional data were analyzed by two methods: by calculating aggregate loss and by simple thresholding. The alignment quality of structural and functional data was also evaluated. RESULTS: Overall, the break area showed a good correlation with aggregate sensitivity loss (ρ = 0.834, P < 0.0001, 95% confidence interval 0.716-0.906) but also with the number of test points below a threshold value (e.g., <20 dB: ρ = 0.843, P < 0.0001, 95% confidence interval 0.755-0.902). Significant misalignment of the MAIA test grid was apparent in 13/48 visits of 7/14 eyes. CONCLUSION: The authors found a good correlation between ellipsoid zone break area and function loss. En face OCT mapping of the ellipsoid zone appears to demonstrate structural change before mesopic microperimetry can detect a focal loss of retinal sensitivity. Thresholding offers a quick alternative to calculating aggregate sensitivity loss.

CHARACTERISTICS OF PIGMENTED LESIONS IN TYPE 2 IDIOPATHIC MACULAR TELANGIECTASIA.

PURPOSE: Pigment in the midretina is a characteristic sign in Type 2 idiopathic macular telangiectasia (MacTel) and is considered to characterize the late stage of the disease. Our aim was to investigate its incidence, and relationship with risk factors for MacTel, including outer retinal vascularization and subretinal neovascular proliferation (SRNV). METHODS: Pigment extent was measured in fundus autofluorescence images of 150 eyes of 75 MacTel probands, using the Region Finder tool of Heidelberg Eye Explorer. A linear mixed model was used to analyze the dynamics of pigment and its associations with other features of the phenotype. The relative incidence of pigment and of outer retinal outer retinal vascularization and SRNV was analyzed within the full MacTel Study cohort (1,244 probands). RESULTS: Mean pigment area at baseline was 0.157 mm (range = 0-1.295 mm, SD = 0.228 mm, n = 101). Progression demonstrated a nonlinear pattern (P < 0.001) at an overall rate of 0.0177 mm/year and was associated with the initial plaque size and with SRNV. There was a strong correlation between fellow eyes (P ≤ 0.0001). In approximately 25% of all SRNV cases, SRNV may coincide with or precede pigment. CONCLUSION: Our data may be useful for refining the current system for staging disease severity in MacTel.

CORRELATION OF OPTICAL COHERENCE TOMOGRAPHY AND MACULAR PIGMENT OPTICAL DENSITY MEASUREMENTS IN TYPE 2 IDIOPATHIC MACULAR TELANGIECTASIA.

PURPOSE: Macular telangiectasia is associated with neurodegenerative changes including focal outer retinal atrophy and a loss of macular pigment (MP). We aimed to investigate whether an association between spectral domain optical coherence tomography neurodegenerative signs and MP abnormalities can be detected. METHODS: Forty-seven eyes of 27 macular telangiectasia Type 2 patients (mean age 66.7 years, range 50-82 years, 12 male) were investigated. An MP pattern was recorded using a dual-wavelength autofluorescence method and classified according to severity (I-III). Outer plexiform, inner nuclear, and photoreceptor layer thickness values were measured in Spectralis spectral domain optical coherence tomography scans. Thickness values were compared with those of a control group of 14 healthy age-matched eyes. RESULTS: Macular pigment redistribution was found to be Class I in 11 eyes, Class II in 28 eyes, and Class III in 8 eyes. More advanced stages of MP loss were associated with a greater, statistically significant thinning of the outer plexiform and inner nuclear layer complex and photoreceptor layers (P ≤ 0.001). Lower absolute levels of MP were also associated with a thinning of the photoreceptor layer. Thinning was restricted to within the parafovea, more severe at temporal eccentricities. CONCLUSION: Our findings support the hypothesis that in macular telangiectasia Type 2 cellular degenerative processes leading to a thinning of these layers also result in reduction and redistribution of MP.

Nigeria normative data for defining glaucoma in prevalence surveys.

PURPOSE: To determine normative values for defining glaucoma in cross-sectional surveys in Nigerian adults. METHODS: Multistage stratified cluster random sampling with probability-proportional-to-size procedures to select a nationally representative sample of 15,027 persons aged ≥ 40 years in 305 clusters across Nigeria. Systematic sampling of 1 in 7 participants gave 1759 who were examined in detail to construct a normative database. The normative subset was used to determine values for vertical cup/disc ratio (VCDR) and intraocular pressure (IOP) for glaucoma diagnosis according to the International Society of Geographical and Epidemiological Ophthalmology (ISGEO) criteria. Examinations included visual field testing by frequency doubling technology (FDT), Goldmann applanation tonometry, and optic disc image grading by Moorfields Eye Hospital Reading Centre. RESULTS: In the normative dataset, 1057/1759 persons (60.1%) had normal FDTs, and constituted the hypernormal. Of these, 851 had VCDR and 973 had IOP measurements taken in both eyes. For category 1 (structural and functional evidence of glaucoma), the 97.5th percentile VCDR was 0.7. For category 2 (advanced structural damage with unproven visual field loss), the 99.5th percentile VCDR was 0.75. In addition, asymmetry in VCDR was 0.1 difference at the 97.5th percentile and 0.2 difference at the 99.5th percentile. Category 3 criteria were used when the optic disc was not visible and field testing not possible; 99.5th percentile IOP is one criterion (28 mmHg). CONCLUSION: While these results do not differentiate between open-angle and angle-closure mechanisms, they can be applied to determine the prevalence of glaucoma in Nigeria and sub-Saharan African countries with similar sociodemographic characteristics.

Ciliary neurotrophic factor for macular telangiectasia type 2: results from a phase 1 safety trial.

PURPOSE: To evaluate the safety and tolerability of intraocular delivery of ciliary neurotrophic factor (CNTF) using an encapsulated cell implant for the treatment of macular telangiectasia type 2. DESIGN: An open-label safety trial conducted in 2 centers enrolling 7 participants with macular telangiectasia type 2. METHODS: The participant's more severely affected eye (worse baseline visual acuity) received the high-dose implant of CNTF. Patients were followed for a period of 36 months. The primary safety outcome was a change in the parameters of the electroretinogram (ERG). Secondary efficacy outcomes were changes in visual acuity, en face measurements of the optical coherence tomography of the disruption in the ellipsoid zone, and microperimetry when compared with baseline. RESULTS: The ERG findings demonstrated a reduction in the amplitude of the scotopic b-wave in 4 participants 3 months after implantation (month 3). All parameters returned to baseline values by month 12 and remained so at month 36 with no clinical impact on dark adaptation. There was no change in visual acuity compared with baseline. The area of the defect as measured functionally by microperimetry and structurally by the en face OCT imaging of the ellipsoid zone loss appeared unchanged from baseline. CONCLUSIONS: The intraocular delivery of CNTF in the encapsulated cell implant appeared to be safe and well tolerated in eyes with macular telangiectasia type 2. Further evaluation in a randomized controlled clinical trial is warranted to test for efficacy.

Multimodal imaging in type 2 idiopathic macular telangiectasia.

BACKGROUND: Macular telangiectasia Type 2 is a bilateral, progressive potentially blinding retinal disease characterized by both vascular and neurodegenerative signs that have been documented using different imaging techniques. The correlation between macular telangiectasia Type 2 signs from various imaging modalities is unknown. Our aim was to investigate the relationship of various macular telangiectasia Type 2 signs using fundus fluorescein angiography, optical coherence tomography and dual-wavelength autofluorescence images. METHODS: Participants were selected from the macular telangiectasia Type 2 Natural History Observation Study, based on a confirmed diagnosis and the availability of images. Signs in fundus fluorescein angiography, dual-wavelength autofluorescence, and optical coherence tomography images were graded according to standardized categories, and agreement among the multimodel imaging was assessed statistically. RESULTS: One hundred and ninety-one eyes of 96 patients were examined. Significant correlations were found between early and late fundus fluorescein angiography (ρ = 0.82, P < 0.0001), luteal pigment loss and early/late fundus fluorescein angiography signs (ρ = 0.52, P < 0.0001 and ρ = 0.62, P < 0.0001, respectively), inner and outer segment break length and pigment loss (Class 1 vs. 2/3, P < 0.0001; Class 2 vs. 3, P = 0.04). Correlation between pigment loss and retinal spaces/atrophic retinal restructuring was fair (κ = 0.25-0.33). Bilateral symmetry was slight to substantial (κ = 0.18-0.62). CONCLUSION: Our data demonstrate the relative extent of neurodegenerative and vascular signs; it may be useful for designing systems for staging disease severity using multimodal imaging and may also provide clues to the pathogenesis of the disease.

Associations between autofluorescence abnormalities and visual acuity in idiopathic macular telangiectasia type 2: MacTel project report number 5.

PURPOSE: The aim of this study was to determine whether typical abnormalities seen on autofluorescence (AF) imaging in patients with macular telangiectasia (MacTel) type 2 are correlated with visual acuity at presentation and with progression of visual loss over a 2-year follow-up period. METHODS: A subgroup of 218 patients (413 eyes) enrolled in the MacTel study that underwent AF imaging was included in the present study. Images were graded at the Moorfields Eye Hospital Reading Center. Recorded AF abnormalities at baseline and at 2 years included the presence of increased AF because of loss of masking at the central macula, localized decreased AF at the end of a retinal vessel, and large area of decreased AF. Best-corrected visual acuity was measured using the Early Treatment for Diabetic Retinopathy chart at baseline and after 2 years. Statistical associations were sought by means of a generalized linear model. RESULTS: Presence of increased macular AF (P = 0.004), a large area of decreased AF (P < 0.001), or decreased AF at the end of a retinal vessel (P < 0.001) at baseline were significantly associated with worse best-corrected visual acuity. Presence of increased macular AF (P < 0.001) or of localized decreased AF at the end of a retinal vessel (P < 0.001) and the absence of a large area of decreased AF (P < 0.001) were predictive of a subtle but significant drop in best-corrected visual acuity at 2 years. CONCLUSIONS: Increased central AF at baseline heralds worse best-corrected visual acuity and predicts further subtle visual loss in a period of 2 years, which, however, does not stand out from the overall slowly progressive natural history of the disease.

Cone photoreceptor definition on adaptive optics retinal imaging.

AIMS: To quantitatively analyse cone photoreceptor matrices on images captured on an adaptive optics (AO) camera and assess their correlation to well-established parameters in the retinal histology literature. METHODS: High resolution retinal images were acquired from 10 healthy subjects, aged 20-35 years old, using an AO camera (rtx1, Imagine Eyes, France). Left eye images were captured at 5° of retinal eccentricity, temporal to the fovea for consistency. In three subjects, images were also acquired at 0, 2, 3, 5 and 7° retinal eccentricities. Cone photoreceptor density was calculated following manual and automated counting. Inter-photoreceptor distance was also calculated. Voronoi domain and power spectrum analyses were performed for all images. RESULTS: At 5° eccentricity, the cone density (cones/mm(2) mean±SD) was 15.3±1.4×10(3) (automated) and 13.9±1.0×10(3) (manual) and the mean inter-photoreceptor distance was 8.6±0.4 µm. Cone density decreased and inter-photoreceptor distance increased with increasing retinal eccentricity from 2 to 7°. A regular hexagonal cone photoreceptor mosaic pattern was seen at 2, 3 and 5° of retinal eccentricity. CONCLUSIONS: Imaging data acquired from the AO camera match cone density, intercone distance and show the known features of cone photoreceptor distribution in the pericentral retina as reported by histology, namely, decreasing density values from 2 to 7° of eccentricity and the hexagonal packing arrangement. This confirms that AO flood imaging provides reliable estimates of pericentral cone photoreceptor distribution in normal subjects.

The IS/OS junction layer in the natural history of type 2 idiopathic macular telangiectasia.

PURPOSE: To document the progression of a break in the photoreceptor inner segment/outer segment (IS/OS) junction layer and its functional correlates over time in the natural history of type 2 idiopathic macular telangiectasia (type 2 MacTel). METHODS: Patients with at least 1 year of follow-up were selected from the MacTel Study. En face images were created by manual segmentation of the IS/OS junctional line in volume scans acquired using a spatial-domain optical coherence tomography retinal imaging unit. Retinal sensitivity thresholds were determined using a retinal microperimeter unit. Aggregate retinal sensitivity loss within IS/OS lesions was calculated. Changes over time in an area of IS/OS defects and retinal sensitivity were analyzed. RESULTS: thirty-nine eyes of 23 patients (mean age: 62.3 ± 9.2 years) were analyzed. Mean follow-up time was 1.9 years (range: 1-3 years). Mean IS/OS break area at baseline was 0.575 mm(2) (SE = 0.092, 95% confidence interval [CI]: 0.394-0.756 mm(2)). The cluster-adjusted mean annual progression rate in IS/OS break area was 0.140 mm(2) (SE = 0.040, 95% CI: 0.062-0.218 mm(2), P < 0.001). Mean aggregate retinal sensitivity loss was at baseline 28.56 dB (SE = 5.43, 95% CI: 17.32-39.80 dB, n = 28), a positive correlation with IS/OS lesion area was present (P < 0.001). The mean annual rate of change in aggregate sensitivity loss was 5.14 dB (SE = 1.51, 95% CI: 2.19-8.10 dB, P < 0.001, n = 37), a significant correlation with lesion area increase was found (P = 0.006). CONCLUSIONS: Both IS/OS break area and rate of enlargement correlate with aggregate retinal sensitivity loss in type 2 MacTel. En face OCT imaging of the IS/OS layer provides a functionally relevant method for documenting disease progression in type 2 MacTel.