Purpose

Basal linear deposit (BLinD) is a thin layer of soft drusen material. To elucidate the biology of extracellular deposits conferring age-related macular degeneration (AMD) progression risk and inform multimodal clinical imaging based on optical coherence tomography (OCT), we examined lipid content and regional prevalence of BLinD, soft drusen, pre-BLinD, and subretinal drusenoid deposit (SDD) in AMD and non-AMD aged eyes. We estimated BLinD volume and illustrated its relation to type 1 macular neovascularization (MNV).

Methods

Donor eyes were classified as early to intermediate AMD (n = 25) and age-matched controls (n = 54). In high-resolution histology, we assessed BLinD/soft drusen thickness at 836 and 1716 locations in AMD and control eyes, respectively. BLinD volume was estimated using solid geometry in donor eyes, one clinically characterized.

Results

BLinD, drusen, type 1 MNV, and fluid occupy the sub-RPE-basal laminar space. BLinD volume in a 3-mm diameter circle may be as much as 0.0315 mm3. Osmophilic lipid was more concentrated in BLinD/drusen than SDD. In the fovea, BLinD/drusen was prevalent in AMD eyes; pre-BLinD was prevalent in control eyes. SDD was low in the fovea and high in perifovea, especially in AMD eyes.

Conclusions

Although invisible, BLinD may presage type 1 MNV. BLinD volume approaches the criterion OCT drusen volume of 0.03 mm3 for AMD progression risk. BLinD culminates years of subfoveal lipid accumulation. SDD is detected relatively late in life, with currently unknown precursors. Deposit topography suggests one outer retinal lipid recycling system serving specialized cone and rod physiology, and its dysregulation in AMD is due to impaired transfer to the circulation.

PURPOSE: To investigate the use of super-resolution imaging techniques to enable telepathology using low-cost commercial cameras. DESIGN: Experimental study. PARTICIPANTS: A total of 139 ophthalmic pathology slides obtained from the Ophthalmic Pathology service at the University of California, Irvine. METHODS: Denoising Diffusion Probabilistic Model (DDPM) was developed to predict super-resolution pathology slide images from low-resolution inputs. The model was pretrained using 150 000 images randomly sampled from the ImageNet dataset. Patch aggregation was used to generate large images with DDPM. The performance of DDPM was evaluated against that of generative adversarial networks (GANs) and Robust UNet, which were also trained on the same dataset. MAIN OUTCOME MEASURES: The performance of models trained to generate super-resolution output images from low-resolution input images can be evaluated by using the mean squared error (MSE) and Structural Similarity Index Measure (SSIM), as well as subjective grades provided by expert pathologist graders. RESULTS: In total, our study included 110 training images, 9 validation images, and 20 testing images. The objective performance scores were averaged over patches generated from 20 test images. The DDPM-based approach with pretraining produced the best results, with an MSE score of 1.35e-5 and an SSIM score of 0.8987. A qualitative analysis of super-resolution images was conducted by expert 3 pathologists and 1 expert ophthalmic microscopist, and the average accuracy of identifying the correct ground truth images ranged from 25% to 70% (with an average accuracy of 46.5%) for widefield images and 25% to 60% (with an average accuracy of 38.25%) for individual patches. CONCLUSIONS: The DDPM-based approach with pretraining is assessed to be effective at super-resolution prediction for ophthalmic pathology slides both in terms of objective and subjective measures. The proposed methodology is expected to decrease the reliance on costly slide scanners for acquiring high-quality pathology slide images, while also streamlining clinical workflow and expanding the scope of ophthalmic telepathology. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Purpose

To determine the abundance and multimodal visibility of drusen and basal linear deposit (BLinD) in early age-related macular degeneration.

Methods

A 69-year-old white man was imaged by color fundus photography and red free photography, fundus autofluorescence, and optical coherence tomography. From en face images, we determined the drusen field, drusen area, and equivalent diameters of individual drusen. From high-resolution light-microscopic histology (6 months after the last clinic visit), we determined the area of drusen, BLinD, and pre-BLinD in a subretinal pigment epithelium-basal lamina lipid field.

Results

In right and left eyes, respectively, BLinD covered 40% and 46% of the lipid field, versus 21% and 14% covered by drusen. The lipid field was covered 60% to 61% by Drusen + BLinD and 65% to 72% by BLinD + pre-BLinD. In the left eye, the drusen area on color fundus photography (0.18 mm) and red free (0.28 mm) was smaller than the drusen area on histology (1.16 mm). Among drusen confirmed by optical coherence tomography, 55.1% and 56.6% were observed on red free and fundus autofluorescence, respectively.

Conclusion

Basal linear deposit covered 1.9 and 3.4-fold more fundus area than soft drusen, silently increasing progression risk. Improved visualization of BLinD and readouts of the retinal pigment epithelium health over lipid will assist population surveillance, early detection, and trial outcome measures.

Background

To explore the role of foveal and parafoveal Müller cells in the morphology and pathophysiology of tractional macular disorders with a mathematical model of mechanical force transmission.

Methods

In this retrospective observational study, spectral-domain optical coherence tomography images of tractional lamellar macular holes and patients with myopic foveoschisis were reviewed and analysed with a mathematical model of force transmission. Parafoveal z-shaped Müller cells were modelled as a structure composed of three rigid rods, named R1, R2 and R3. The angle formed between the rods was referred to as θ . R1, R2 and R3 lengths as well as the variation of the angle θ were measured and correlated with best corrected visual acuity (BCVA).

Results

In tractional lamellar macular holes, there was a significant reduction of the angle θ towards the foveal centre (p<0.001). By contrast, there were no significant differences in θ in myopic foveoschisis (p=0.570). R2 segments were more vertical in myopic foveoschisis. There was a significant association between lower θ angles at 200 µm temporal and nasal to the fovea and lower BCVA (p<0.001 and p=0.005, respectively). The stiffness of parafoveal Müller cells was predicted to be function of the angle θ , and it grew very rapidly as the θ decreased.

Conclusion

Parafoveal Müller cells in the Henle fibre layer may guarantee structural stability of the parafovea by increasing retinal compliance and resistance to mechanical stress. Small values of the angle θ were related to worse BCVA possibly due to damage to Müller cell processes and photoreceptor's axons.