Comparison of Widefield OCT Angiography Features Between Severe Non-Proliferative and Proliferative Diabetic Retinopathy.

INTRODUCTION: There is a high and ever-increasing global prevalence of diabetic retinopathy (DR) and invasive imaging techniques are often required to confirm the presence of proliferative disease. The aim of this study was to explore the images of a rapid and non-invasive technique, widefield optical coherence tomography angiography (OCT-A), to study differences between patients with severe non-proliferative and proliferative DR (PDR). METHODS: We conducted an observational longitudinal study from November 2022 to March 2023. We recruited 75 patients who were classified into a proliferative group (28 patients) and severe non-proliferative group (47 patients). Classification was done by specialist clinicians who had full access to any multimodal imaging they required to be confident of their diagnosis, including fluorescein angiography. For all patients, we performed single-shot 4 × 4 and 10 × 10 mm (widefield) OCT-A imaging and when possible, the multiple images required for mosaic 17.5 × 17.5 mm (ultra widefield) OCT-A imaging. We assessed the frequency with which proliferative disease was identifiable solely from these OCT-A images and used custom-built MATLAB software to analyze the images and determine computerized metrics such as density and intensity of vessels, foveal avascular zone, and ischemic areas. RESULTS: On clinically assessing the OCT-A 10 × 10 fields, we were only able to detect new vessels in 25% of known proliferative images. Using ultra-widefield mosaic images, however, we were able to detect new vessels in 100% of PDR patients. The image analysis metrics of 4 × 4 and 10 × 10 mm images did not show any significant differences between the two clinical groups. For mosaics, however, there were significant differences in the capillary density in patients with PDR compared to severe non-PDR (9.1% ± 1.9 in the PDR group versus 11.0% ± 1.9 for severe group). We also found with mosaics a significant difference in the metrics of ischemic areas; average area of ischemic zones (253,930.1 ± 108,636 for the proliferative group versus 149,104.2 ± 55,101.8 for the severe group. CONCLUSIONS: Our study showed a high sensitivity for detecting PDR using only ultra-widefield mosaic OCT-A imaging, compared to multimodal including fluorescein angiography imaging. It also suggests that image analysis of aspects such as ischemia levels may be useful in identifying higher risk groups as a warning sign for future conversion to neovascularization.

Improvements in Diabetic Neuropathy and Nephropathy After Bariatric Surgery: a Prospective Cohort Study.

PURPOSE: There are limited data on the impact of bariatric surgery on microvascular complications of type 2 diabetes (T2D), particularly diabetic neuropathy. We assessed microvascular complications (especially neuropathy) in obese patients with T2D before and 12 months after bariatric surgery. MATERIALS AND METHODS: This was a prospective observational cohort study. Measurements of neuropathy symptom profile (NSP), neuropathy disability score (NDS), vibration (VPT), cold (CPT) and warm (WPT) perception thresholds, nerve conduction studies (NCS) and corneal confocal microscopy (CCM) to quantify corneal nerve fibre density (CNFD), branch density (CNBD) and fibre length (CNFL); urinary albumin/creatinine ratio (uACR), estimated glomerular filtration rate (eGFRcyst-creat) and retinal grading were taken. RESULTS: Twenty-six (62% female; median age 52 years) obese patients with T2D were recruited. Body mass index (BMI) (47.2 to 34.5 kg/m2; p < 0.001) decreased post-operatively. There were improvements in CNFD (27.1 to 29.2/mm2; p = 0.005), CNBD (63.4 to 77.8/mm2; p = 0.008), CNFL (20.0 to 20.2/mm2; p = 0.001), NSP (3 to 0/38; p < 0.001) and eGFRcyst-creat (128 to 120 ml/min; p = 0.015) post-bariatric surgery. Changes in (Δ) triglycerides were independently associated with ΔCNFL (ß = - 0.53; p = 0.024) and Δsystolic blood pressure (ß = 0.62;p = 0.017), and %excess BMI loss (ß = - 0.004; p = 0.018) were associated with ΔeGFRcyst-creat. There was no significant change in NDS, VPT, CPT, WPT, NCS, uACR or retinopathy status. Glomerular hyperfiltration resolved in 42% of the 12 patients with this condition pre-operatively. CONCLUSION: Bariatric surgery results in improvements in small nerve fibres and glomerular hyperfiltration in obese people with T2D, which were associated with weight loss, triglycerides and systolic blood pressure, but with no change in retinopathy or uACR at 12 months.

New Findings in Diabetic Maculopathy and Proliferative Disease by Swept-Source Optical Coherence Tomography Angiography.

PURPOSE: To describe the optical coherence tomography (OCT) angiography (OCTA) features of diabetic retinopathy. METHODS: Retrospective serial case reports were examined of patients who underwent routine clinical examination and OCTA with both DRI OCT Atlantis prototype and Triton Swept-Source OCT of the posterior pole and mid-periphery. When considered necessary, fluorescein fundus angiography (FFA) with OPTOS California wide-field imaging was performed. The findings were compared with the current literature. RESULTS: Forty-three consecutive patients (86 eyes) were evaluated. Fourteen of these patients (28 eyes) underwent an additional FFA examination due to advanced retinopathy signs, such as diabetic macular edema, ischemia or neovascularization (NV). OCTA was able to detect the microvascular lesions observed on color fundus images in the whole sample. Thirty-six of the 86 eyes showed foveal avascular zone enlargement on OCTA. Microvascular lesions, diabetic macular edema, and NV of the optic disc observed on FFA were also detected on OCTA in all cases (28/28 eyes). Features of NV elsewhere were detected on FFA in 16/28 eyes. Ten of the 16 eyes had signs of NV within the 100 central degrees, and OCTA was able to detect these signs in 9 of the eyes. CONCLUSION: OCTA is an effective noninvasive imaging technique that can provide additional information regarding the localization and morphology of vascular lesions in all cases of NV of the optic disc and in more than half of cases of NV elsewhere, suggesting that it is a noninferior technique for the study of posterior pole alterations compared with FFA, which remains the gold standard and is fundamental for the study of the retinal periphery.

In vivo imaging of cortical vitreous using 1050-nm swept-source deep range imaging optical coherence tomography.

PURPOSE: To image the cortical vitreous, determine the prevalence of the bursa premacularis and space of Martegiani, and measure the dimensions of the bursa using the new 1050-nm swept-source deep range imaging optical coherence tomography (DRI OCT-1 Atlantis). DESIGN: Retrospective cross-sectional study. METHODS: One hundred and nineteen consecutive patients (5-100 years) underwent an OCT scan using 1050-nm swept-source deep range imaging optical coherence tomography. Prevalence of the bursa premacularis and space of Martegiani and the stage of posterior vitreous detachment (PVD) were determined. The horizontal (width) and anteroposterior (depth) dimensions of the bursa were recorded along with the patient's age. RESULTS: A bursa was detected in 57.1% (136/238) of eyes. The bursa and space of Martegiani coexisted in 97.8% of eyes. Prevalence of detected bursa was 84.5% in eyes with either no PVD or perifoveal PVD only; the prevalence fell with further increases in the extent of PVD. Prevalence of detected bursa was 75.4% in patient group aged 0-60 years and 38% in the group aged 60-100 years. Mean width was 7001 µm (range: 3354-10 316 µm, SD: 1412 µm). Mean depth was 416 µm (range: 31-1189 µm, SD: 187 µm). Width and depth of the bursa did not correlate with age (R(2) width = 0.0316; R(2) depth = 0.0108). Bilateral bursa tended to be symmetrical in width but less so in depth (R(2) width = 0.63, P < .001; R(2) depth = 0.33, P < .001). CONCLUSION: Swept-source OCT has allowed us to demonstrate the almost invariable coexistence of the bursa premacularis and space of Martegiani. Swept-source OCT can image both in patients from as early as the first to as late as the tenth decade of life.

Peripapillary choroidal neovascularisation in the context of ocular syphilis is sensitive to combination antibiotic and corticosteroid treatment.

Peripapillary choroidal neovascularisation (CNV) in the context of ocular syphilis is exceptional and little is known about its natural history and optimal therapeutic management. We report here a case of right eye peripapillary CNV with subretinal fluid encroaching on the fovea in a patient with mild bilateral ocular inflammation and cystoid macular oedema (CMO) in his contralateral eye. Extensive investigations revealed positive serology for active syphilitic infection. The patient received treatment with intravenous benzylpenicillin according to the algorithm for neurosyphilis complemented with oral corticosteroids as prophylaxis against Jarisch-Herxsheimer reaction for a period of 17 days. On the 15th day, receding of subretinal fluid in his right eye to a small pocket around the optic disc was identified as well as resolution of left eye CMO. We suggest that a course of antibiotic treatment for neurosyphilis with the addition of oral corticosteroids may be an effective therapeutic option for CNV in the context of ocular syphilis and thus more invasive treatment approaches are not warranted.

Comparison of lectin binding of drusen, RPE, Bruch's membrane, and photoreceptors.

PURPOSE: Drusen are deposits located between the retinal pigment epithelium and Bruch's membrane in age-related maculopathy. They are believed to be photoreceptor byproducts that are incompletely metabolized by the retinal pigment epithelium. This study therefore compares the lectin histochemistry of drusen, photoreceptors, retinal pigment epithelium, and Bruch's membrane. METHODS: Semithin sections of three eyes with age-related maculopathy were studied using 19 biotinylated lectins and an avidin-peroxidase-revealing system with and without neuraminidase pretreatment. RESULTS: High mannose, bi and tri-antennary nonbisected and bisected complex N-glycan, N-acetyl glucosamine and galactose were expressed by drusen, retinal pigment epithelium, Bruch's membrane, and photoreceptors while N-acetyl galactosamine and fucose were absent; treatment with neuraminidase exposed subterminal galactose in both sites and sparse N-acetyl galactosamine residues in drusen alone. Overall, there were striking similarities between the lectin binding of drusen, retinal pigment epithelium, and the photoreceptor outer segments, though cone outer segments were distinct in some features of their O-linked glycosylation. CONCLUSIONS: The results suggest that the pathogenesis of drusen is a combined mechanism, involving photoreceptors, Bruch's membrane, and the retinal pigment epithelium.

Oligosaccharide composition is similar in drusen and dense deposits in membranoproliferative glomerulonephritis type II.

Drusen are a feature of age-related macular degeneration (AMD). Lesions similar in appearance to drusen are also found in the fundi of patients with membranoproliferative glomerulonephritis type II (dense deposit disease, DDD). The lamina densa of the glomerular basement membrane, in DDD, is transformed into an electron-dense structure by deposition of microscopically homogeneous material. Our study sought to compare the saccharide composition of drusen and dense deposits in the formalin-fixed, paraffin-embedded tissue from the eye and kidney. Six eye specimens were obtained from patients diagnosed with AMD but another eye was obtained from a patient with partial lipodystrophy, who died after renal failure presumably because of DDD. The kidney specimens were from three biopsy-proven cases of DDD. Glycosylation patterns were measured by the binding of 19 biotinylated lectins before and after neuraminidase pre-treatment. High mannose, bi/tri-antennary non-bisected and bisected complex N-glycan, N-acetyl glucosamine, galactose, and sialic acid residues were found in both drusen and dense deposits. Treatment with neuraminidase exposed subterminal galactose in both sites and sparse N-acetyl galactosamine residues in drusen alone. Our study found similar pathologic oligosaccharide structures in the eye and kidney, suggesting that drusen may be a common end result of retinal and glomerular disease.

Glycoproteins of drusen and drusen-like lesions.

Drusen are a marker of age-related macular degeneration (AMD). Lesions similar to drusen, both in histology and their clinical appearance, are also seen in choroidal tumours, chronic inflammatory and degenerative conditions of the eye, and in mesangiocapillary glomerulonephritis type II (MCGN-II). This study aims to compare the saccharide composition of these drusen-like lesions in the various ocular pathological groups and in MCGN-II. Formalin fixed and paraffin wax embedded tissue from 21 eyes was studied. The histological diagnoses included AMD, retinal detachment, phthisis bulbi following failed retinal detachment surgery, malignant melanoma, long-standing uveitis, glaucoma and MCGN II. Glycosylation was examined using a panel of twenty biotinylated lectins and an avidin-peroxidase DAB-cobalt revealing system, with and without neuraminidase pre-treatment. High mannose, bi/tri-nonbisected and bisected complex N-glycan, N-acetyl glucosaminyl, galactosyl and sialyl residues were found to be expressed by drusen, while treatment with neuraminidase exposed subterminal N-acetyl galactosamine and galactosyl residues. Similar binding patterns were found in the various pathological groups studied. As there was no significant difference in the lectin-binding pattern in drusen in different pathologies, a common pathogenesis or at least a final common pathway for the elaboration of carbohydrate components of drusen is suggested.