RETINAL HYPERREFLECTIVE FOCI IN TYPE 1 DIABETES MELLITUS.

PURPOSE: To investigate hyperreflective foci (HF) on spectral-domain optical coherence tomography in patients with Type 1 diabetes mellitus across different stages of diabetic retinopathy (DR) and diabetic macular edema (DME) and to study clinical and morphological characteristics associated with HF. METHODS: Spectral-domain optical coherence tomography scans and color fundus photographs were obtained of 260 patients. Spectral-domain optical coherence tomography scans were graded for the number of HF and other morphological characteristics. The distribution of HF across different stages of DR and DME severity were studied. Linear mixed-model analysis was used to study associations between the number of HF and clinical and morphological parameters. RESULTS: Higher numbers of HF were found in patients with either stage of DME versus patients without DME (P < 0.001). A trend was observed between increasing numbers of HF and DR severity, although significance was only reached for moderate nonproliferative DR (P = 0.001) and proliferative DR (P = 0.019). Higher numbers of HF were associated with longer diabetes duration (P = 0.029), lower high-density lipoprotein cholesterol (P = 0.005), and the presence of microalbuminuria (P = 0.005). In addition, HF were associated with morphological characteristics on spectral-domain optical coherence tomography, including central retinal thickness (P = 0.004), cysts (P < 0.001), subretinal fluid (P = 0.001), and disruption of the external limiting membrane (P = 0.018). CONCLUSION: The number of HF was associated with different stages of DR and DME severity. The associations between HF and clinical and morphological characteristics can be of use in further studies evaluating the role of HF as a biomarker for disease progression and treatment response.

Imaging diabetic retinal disease: clinical imaging requirements.

Diabetic retinopathy (DR) is a sight-threatening complication of diabetes mellitus (DM) and it contributes substantially to the burden of disease globally. During the last decades, the development of multiple imaging modalities to evaluate DR, combined with emerging treatment possibilities, has led to the implementation of large-scale screening programmes resulting in improved prevention of vision loss. However, not all patients are able to participate in such programmes and not all are at equal risk of DR development and progression. In this review, we discuss the relevance of the currently available imaging modalities for the evaluation of DR: colour fundus photography (CFP), ultrawide-field photography (UWFP), fundus fluorescein angiography (FFA), optical coherence tomography (OCT), OCT angiography (OCTA) and functional testing. Furthermore, we suggest where a particular imaging technique of DR may aid the evaluation of the disease in different clinical settings. Combining information from various imaging modalities may enable the design of more personalized care including the initiation of treatment and understanding the progression of disease more adequately.

Long-term outcomes of vitrectomy for proliferative diabetic retinopathy.

PURPOSE: To investigate the long-term outcomes of patients who underwent vitrectomy for proliferative diabetic retinopathy. METHODS: Cumulative incidences were calculated for low vision (<0.3), re-vitrectomy in the study eye and fellow eye vitrectomy. To identify potential prognostic factors that associate with these outcomes, we used multivariable Cox regression models. RESULTS: In a total of 217 patients, we found 1-, 5- and 10-year cumulative incidences of low vision in the study eye of 24%, 31% and 39%, respectively. For both eyes, these rates were, respectively, 10%, 14% and 14%. Low vision in both eyes was associated with higher age and worse contralateral visual acuity. The 1-, 5- and 10-year cumulative incidences for re-vitrectomy in the study eye were 16%, 27% and 27%, respectively, and for a vitrectomy in the fellow eye 24%, 40% and 54%, respectively. Re-vitrectomy of the study eye was associated with worse contralateral visual acuity, while vitrectomy of the fellow eye was associated with shorter diabetes duration, worse contralateral visual acuity, higher HbA1c level and worse diabetic retinopathy severity stage of the fellow eye. CONCLUSION: Functional visual acuity in at least one eye was achieved or preserved in most patients. After 10 years, about a quarter of all patients underwent a re-vitrectomy, while more than half of the patients needed a vitrectomy of the fellow eye. Knowledge of these long-term outcomes is essential when counselling patients for a vitrectomy.

Validation of a model for the prediction of retinopathy in persons with type 1 diabetes.

BACKGROUND/AIM: To validate a previously developed model for prediction of diabetic retinopathy (DR) for personalised retinopathy screening in persons with type 1 diabetes. METHODS: Retrospective medical data of persons with type 1 diabetes treated in an academic hospital setting were used for analysis. Sight-threatening retinopathy (STR) was defined as the presence of severe non-proliferative DR, proliferative DR or macular oedema. The presence and grade of retinopathy, onset of diabetes, systolic blood pressure, and levels of haemoglobin A1c were used to calculate an individual risk estimate and personalised screening interval. In persons with STR, the occurrence was compared with the calculated date of screening. The model's predictive performance was measured using calibration and discrimination techniques. RESULTS: Of the 268 persons included in our study, 24 (9.0%) developed STR during a mean follow-up of 4.6 years. All incidences of STR occurred after the calculated screening date. By applying the model, the mean calculated screening interval was 30.5 months, which is a reduction in screening frequency of 61% compared with annual screening and 21% compared with biennial screening. The discriminatory ability was good (Harrell's C-statistic=0.82, 95% CI 0.74 to 0.90), and calibration showed an overestimation of risk in persons who were assigned to a higher risk for STR. CONCLUSION: This validation study suggests that a screening programme based on the previously developed prediction model is safe and efficient. The use of a personalised screening frequency could improve cost-effectiveness of diabetic eye care.

Ophthalmological findings in facioscapulohumeral dystrophy.

Ophthalmological abnormalities in facioscapulohumeral dystrophy may lead to treatable vision loss, facilitate diagnostics, could help unravelling the pathophysiology and serve as biomarkers. In this study, we provide a detailed description of the ophthalmological findings in a well-defined cohort of patients with facioscapulohumeral dystrophy using state of the art retina imaging techniques. Thirty-three genetically confirmed patients (aged 7-80 years) and 24 unrelated healthy controls (aged 6-68 years) underwent clinical ophthalmological examination, fundus photography, optical coherence tomography/angiography, genotyping and neurological examination. All patients had normal corrected visual acuity and normal intraocular pressure. In 27 of the 33 patients, weakness of the orbicularis oculi was observed. Central retinal pathology, only seen in patients and not in healthy controls, included twisting (tortuosity) of the retinal arteries in 25 of the 33 patients and retinal pigment epithelium defects in 4 of the 33 patients. Asymmetrical foveal hypoplasia was present in three patients, and exudative abnormalities were observed in one patient. There was a correlation between the severity of retinal tortuosity and the D4Z4 repeat array size (R 2 = 0.44, P < 0.005). Follow-up examination in a subgroup of six patients did not show any changes after 2 years. To conclude, retinal abnormalities were frequent but almost always subclinical in patients with facioscapulohumeral dystrophy and consisted primarily of arterial tortuosity and foveal abnormalities. Retinal tortuosity was seen in the retinal arterioles and correlated with the D4Z4 repeat array size, thereby providing clinical evidence for an underlying genetic linkage between the retina and facioscapulohumeral dystrophy.

Risk factors for development and progression of diabetic retinopathy in Dutch patients with type 1 diabetes mellitus.

PURPOSE: To investigate risk factors for the development and progression of diabetic retinopathy (DR) and long-term visual outcomes in Dutch patients with type 1 diabetes mellitus (T1DM). METHODS: Cumulative incidences were calculated for DR, vision-threatening DR (VTDR), defined as (pre)proliferative DR and diabetic macular oedema, and best-corrected visual acuity (BCVA) <0.5 and <0.3 at the most recent eye examination. The following factors were assessed: duration of diabetes, age of onset of T1DM, gender, mean HbA1c, HbA1c variability (defined as coefficient of variation of five separate HbA1c measurements), mean arterial blood pressure, body mass index, albuminuria and lipid profile. We used multivariable Cox regression models to identify factors associated with DR development and progression to VTDR. RESULTS: We found 25-year cumulative incidences of 63% for DR, 21% for VTDR, 2% for BCVA <0.5, and 1% for BCVA <0.3. Mean HbA1c (HR 1.023, p < 0.001), HbA1c variability (HR 1.054, p < 0.001), age of onset of T1DM (HR 1.024, p < 0.001), HDL cholesterol (HR 0.502, p = 0.002) and total cholesterol (HR 1.210, p = 0.029) showed an independent association with faster development of any form of DR. The mean HbA1c (HR 1.023, p < 0.001) and the presence of albuminuria (HR 2.940, p = 0.028) were associated with faster progression to VTDR. CONCLUSION: These data show relatively low cumulative incidences of DR, VTDR and visual impairment. Higher mean HbA1c, HbA1c variability, age of onset of T1DM and total cholesterol were independently associated with the risk of DR development, and a protective association was found for HDL cholesterol in subjects with T1DM. Mean HbA1c and presence of albuminuria were associated with progression of DR.

Hyperreflective foci on optical coherence tomography associate with treatment outcome for anti-VEGF in patients with diabetic macular edema.

PURPOSE: To investigate the relationship between baseline number of hyperreflective foci (HF) on spectral domain optical coherence tomography (SD-OCT) in patients with diabetic macular edema (DME), as well as the dynamics of HF during treatment with anti-vascular endothelial growth factor (VEGF), and treatment response. METHODS: We evaluated patients diagnosed with DME scheduled for treatment with intravitreal bevacizumab. Eyes were classified as adequate or insufficient treatment responders based on logMAR visual acuity improvement and central retinal thickness (CRT) decrease after three consecutive injections. Associations between number of HF at baseline and treatment response, the change in HF over the course of treatment, and the distribution of HF within the retinal layers were evaluated. RESULTS: In 54 eyes of 41 patients, mean number of HF and CRT decreased after intravitreal treatment with bevacizumab (p = 0.002 and p<0.001 respectively). Decrease in CRT after 3 months was independently associated with a higher number of HF at baseline (estimated effect -2.61, 95% CI [-4.42--0.31], p = 0.006). Eyes with adequate treatment response presented with more HF at baseline (OR 1.106, 95% CI [1.012-1.210], p = 0.030) than eyes with insufficient treatment response. Most HF were located within the inner retinal layers, and decrease of HF was mostly due to a decrease of inner retinal HF. CONCLUSIONS: In patients with DME treated with anti-VEGF, higher baseline numbers of HF have predictive value for treatment response in terms of visual acuity improvement and CRT decrease after 3 months. In addition, HF were responsive to anti-VEGF therapy.

Morphological and topographical appearance of microaneurysms on optical coherence tomography angiography.

AIMS: To investigate retinal microaneurysms in patients with diabetic macular oedema (DME) by optical coherence tomography angiography (OCTA) according to their location and morphology in relationship to their clinical properties, leakage on fundus fluorescein angiography (FFA) and retinal thickening on structural OCT. METHODS: OCTA and FFA images of 31 eyes of 24 subjects were graded for the presence of microaneurysms. The topographical and morphological appearance of microaneurysms on OCTA was evaluated and classified. For each microaneurysm, the presence of focal leakage on FFA and associated retinal thickening on OCT was determined. RESULTS: Of all microaneurysms flagged on FFA, 295 out of 513 (58%) were also visible on OCTA. Microaneurysms with focal leakage and located in a thickened retinal area were more likely to be detected on OCTA than not leaking microaneurysms in non-thickened retinal areas (p=0.001). Most microaneurysms on OCTA were seen in the intermediate (23%) and deep capillary plexus (22%). Of all microaneurysms visualised on OCTA, saccular microaneurysms were detected most often (31%), as opposed to pedunculated microaneurysms (9%). Irregular, fusiform and mixed fusiform/saccular-shaped microaneurysms had the highest likeliness to leak and to be located in thickened retinal areas (p<0.001, p<0.001 and p=0.001). CONCLUSIONS: Retinal microaneurysms in DME could be classified topographically and morphologically by OCTA. OCTA detected less microaneurysms than FFA, and this appeared to be dependent on leakage activity and retinal thickening. Morphological appearance of microaneurysms (irregular, fusiform and mixed saccular/fusiform) was associated with increased leakage activity and retinal thickening.

Deep learning approach for the detection and quantification of intraretinal cystoid fluid in multivendor optical coherence tomography.

We developed a deep learning algorithm for the automatic segmentation and quantification of intraretinal cystoid fluid (IRC) in spectral domain optical coherence tomography (SD-OCT) volumes independent of the device used for acquisition. A cascade of neural networks was introduced to include prior information on the retinal anatomy, boosting performance significantly. The proposed algorithm approached human performance reaching an overall Dice coefficient of 0.754 ± 0.136 and an intraclass correlation coefficient of 0.936, for the task of IRC segmentation and quantification, respectively. The proposed method allows for fast quantitative IRC volume measurements that can be used to improve patient care, reduce costs, and allow fast and reliable analysis in large population studies.

Automatic detection of the foveal center in optical coherence tomography.

We propose a method for automatic detection of the foveal center in optical coherence tomography (OCT). The method is based on a pixel-wise classification of all pixels in an OCT volume using a fully convolutional neural network (CNN) with dilated convolution filters. The CNN-architecture contains anisotropic dilated filters and a shortcut connection and has been trained using a dynamic training procedure where the network identifies its own relevant training samples. The performance of the proposed method is evaluated on a data set of 400 OCT scans of patients affected by age-related macular degeneration (AMD) at different severity levels. For 391 scans (97.75%) the method identified the foveal center with a distance to a human reference less than 750 µm, with a mean (± SD) distance of 71 µm ± 107 µm. Two independent observers also annotated the foveal center, with a mean distance to the reference of 57 µm ± 84 µm and 56 µm ± 80 µm, respectively. Furthermore, we evaluate variations to the proposed network architecture and training procedure, providing insight in the characteristics that led to the demonstrated performance of the proposed method.